“This drug is just unbelievably potent in killing tumor cells.”
– Ashok Saluja, study author
The “Thunder God Vine” is a perennial plant, also known as Lei Gong Teng, that grows wild in China, Japan and Korea. It has been used in traditional Chinese medicine dating back thousands of years for treating inflammatory conditions such as arthritis (Caspi, et al., 2013). Recent scientific research has validated ancestral knowledge of the plant’s broad-spectrum of medicinal values, including its anti-inflammatory properties (Lee, et al., 2015), where one study found that in patients with poor lung function and painful arthritis, lung function improved and joint pain was reduced (Wan, et al., 2016). It’s ability to relieve pain has been confirmed by other researchers (Yang, et al., 2014), and a number of other positive effects can be heralded about this botanical marvel, including the slowing of autoimmune disease progression (Wang, et al., 2015), prevention of brain degeneration (Choi, et al., 2014), a weight loss reduction of 45% in obese mice (Liu, et al., 2015), and prevention of bone loss commonly caused by cancer (Park, et al., 2014). And as it turns out, certain compounds derived from the Thunder God Vine have recently been shown to be potent anti-cancer medicines.
Thunder God Vine vs Cancer
In 2012, Joanne was diagnosed with a form of breast cancer called Invasive Ductal Carcinoma. After being treated with surgery, chemotherapy, and radiation, her condition worsened, and in 2014, her cancer had spread and she was diagnosed with Stage 4 Bone cancer and lymph node cancer. Having lost all faith in chemotherapy, she knew she needed another option, and thankfully, when she contacted Timothy Telymonde of cureeveryone.org, he introduced her to the Thunder God Vine. After ingesting 3 to 4 tablespoons per day for three and a half months, her tumor markers dropped 30%, her bone and back pain disappeared, and even her complexion improved. “I feel fantastic, I have energy that I didn’t have before, I’m sleeping better, mentally I feel fantastic, I’m not depressed, I don’t have anxiety, overall, I just feel a good state of mental health and physical health,” declared Joanne in a video interview.
More than 200 bioactive medicinal properties have been isolated from the Thunder God Vine (Luo, et al., 2014), and there will likely be more in the future, but in this chapter, we are going to focus on the substances that have been most scientifically validated thus far – Celastrol, Triptolide, TG, and Minnelide.
Scientific research has confirmed that Celastrol, an oil-extract from the root bark of the Thunder God Vine, in low doses, stops the spread of breast cancer1, lung cancer2, and throat cancer cells3, and triggers apoptotic cell death in bone cancer4,9, liver cancer5, multiple types of mouth cancer6, lung cancer7, breast cancer8,10, and one study added to the list blood cancer, stomach cancer, prostate cancer, kidney cancer, head and neck cancer, skin cancer, and brain cancer11. Even two types of lung cancer cells that developed a complete resistance to chemotherapy were defeated by Celastrol12, and, In mice induced with colon cancer, Celastrol stopped cancer growth13 and triggered cancer cell death in mice induced with human liver cancer, without side effects14. Similarly, healthy human liver cancer cells were found unharmed by the dose needed to kill cancer cells15, and one unique study found that the anti-cancer effects of Tumor necrosis factor-α were enhanced by the addition of Celastrol16. Since the bioavailability of Celastrol is limited by its lack of solubility in water, a few novel delivery approaches have been tested with great success. Celastrol enclosed in tiny fat bubbles called liposomes17, nano-sized polymer carriers18, and sugar-decorated nanoparticles19 all improved intestinal absorption and increased its effectiveness.
- 1. Celastrol, in a 2011 study from Seoul, Korea, was added to human breast cancer cells to determine whether or not the substance could prevent the disease from spreading. As indicated by their results, the substance successfully suppressed breast cancer cell migration and invasion. (Kim, et al., 2011)
- 2. A Chinese research group did an experiment with Celastrol in 2015 to assess its ability to stop the spread (metastasis) of lung cancer. The results showed that Celastrol inhibited the metastasis of lung cancer cells. (Xu, et al., 2015)
- 3. The effects of Celastrol on throat cancer were investigated in an experiment from 2015 by a pair of Chinese researchers, who showed that Celastrol prevented the spread of esophageal cancer. (Xu, et al., 2015)
- 4. A study from Nanchang University, China in 2015 was undertaken to determine the effect of Thunder God Vine extract Celastrol on bone cancer cells and to elucidate exactly how the medicine works. X. Yu and his colleagues observed Celastrol significantly inhibit growth and trigger apoptosis in the cancer cells “via the mitochondrial-dependent pathway”. (Yu, et al., 2015)
- 5. A study from February 2015 tested Celastrol’s effects on liver cancer cells, and the findings were published in The American Journal of Chinese Medicine. Investigators found that the substance slowed growth and caused apoptosis, or cell death, in the cancer cells. (Li, et al., 2015)
- 6. A study from the Children’s Hospital in Detroit, Michigan in 2015 analyzed the effects of Celastrol and Dihydrocelastrol on mouth cancer cells, and found that in numerous cancer cell lines, both substances were potent inducers of cancer cell death. (Fribley, et al., 2015)
- 7. China was the home of a study in 2011, where a team of researchers, led by H Mou, investigated the effects of Celastrol on cultured human lung cancer cells. Celastrol inhibited growth and triggered apoptosis in the human lung cancer cells in vitro. (Mou, et al., 2011)
- 8. The Bone Research Group out of Edinburgh, United Kingdom studied the effects of Celastrol (and a few other substances) on the spread of breast cancer cells in a 2009 study. Their research found that Celastrol inhibited the growth and induced apoptosis in breast tumor cells, and quite impressively, administration of Celastrol reduced bone loss in rats that had been breast cancer induced. (Idris, et al., 2009)
- 9. Researchers from Nanchang, China investigated the effects of Celastrol on bone cancer in a 2015 study published in Oncology Reports. “We found that celastrol significantly inhibited the growth of osteosarcoma cells in a dose-dependent manner” reported researchers, “the results indicate that celastrol inhibits the proliferation of human osteosarcoma cancer cells by inducing apoptosis via the mitochondrial-dependent pathway.” (Yu, et al., 2015)
- 10. Friday, October 10, 2014 was the day that Jung Joon Lee and 5 other researchers published a study in which they used Celastrol on human breast cancer cells, and found that the treatment successfully eliminated breast cancer cells by way of apoptotic induction. (Mi, et al., 2014)
- 11. In 2011, a group of scientists from Singapore investigated the effects of Celastrol on a wide variety of cancer cells. It was found that, in low doses, Celastrol inhibited the spread of cancer and caused cancer cell death in the following types of cancer cells: blood cancer, liver cancer, stomach cancer, prostate cancer, kidney cancer, head and neck cancer, lung cancer, skin cancer, brain cancer, and breast cancer. (Kannaiyan, et al., 2011)
- 12. In a 2014 study out of China, research was conducted using two different types of chemotherapy-resistant lung cancer cells (cells that had developed a complete resistance to chemotherapy) treated with Celastrol, and investigators witnessed cell death in both types of cancer cells. (Fan, et al., 2014)
- 13. Two types of colon cancer cells and two types of colon cancer-induced mice were treated with Celastrol in a study by Chinese researchers in 2016. Treatment with Celastrol for 14 weeks stopped cancer cells from spreading and “significantly increased” survival in mice. Celastrol was also very effective at inhibiting inflammatory responses. (Lin, et al., 2015)
- 14. It has been established that the activation of the gene STAT3 is critical for cancer to survive and grow, so a study from Singapore in 2012 investigated whether or not Celastrol could inhibit the gene. An in vivo test using Celastrol was also done on mice induced with human liver cancer. P Rajendran and his colleagues found that Celastrol inhibited the cancer-promoting STAT3 gene, and in the cancer mice, it inhibited cancer spread and caused cancer cell death, without any negative side effects. (Rajendran, et al., 2012)
- 15. A group of Chinese scientists, seeking to uncover the mechanisms behind the anti-cancer properties of Celastrol, conducted a 2014 study and made breakthrough discoveries regarding how Celastrol asserts its anti-cancer effects. (Due to the complexity of this research, see the study abstract for more). Information about the safety of Celastrol was also unearthed in this study, which reported “A cytotoxic dose of Celastrol for cancer cells did not display cytotoxicity in LO2 normal human liver cells,” meaning cancer cells were killed, and healthy cells were unharmed. (Han, et al., 2014)
- 16. A 2014 study published in the journal PLOS ONE combined Celastrol with Tumor necrosis factor-α (TNF-α), an anti-cancer substance, and after adding them to breast cancer cells in vitro, researchers confirmed that the anti-cancer activities of TNF-α were enhanced by Celastrol. (Lu, et al., 2014)
- 17. Since Celastrol, like Triptolide, is poorly soluble in water, researchers from Jiangsu, China experimented with a novel drug delivery system in a 2011 study, published in the journal Molecules. By encapsulating the Celastrol inside tiny bubbles of fat called liposomes, they were able to increase absorption through the intestinal wall, and found that the Celastrol-loaded liposomes effectively inhibited tumor growth in laboratory mice. (Song, et al., 2011)
- 18. In 2015, experimenters encircled Celastrol with nano-sized polymers and tested its effects on prostate cancer. It was found that the substance inhibited the spread of 3 different types of prostate cancer cells, and remarkably, the nanoparticle carriers “significantly increased” its toxicity to cancer cells. (Sanna, et al., 2015)
- 19. Since tumors consume sugar at rates much higher than normal cells, sugar-decorated silica nanoparticles were formed as delivery vehicles for Celastrol in a study from Turku, Finland in 2015. Researchers demonstrated that the anti-cancer activity of Celastrol delivered by sugar vehicles was “significantly enhanced”. (Niemelä, et al., 2015)
Efforts from scientists across the world have proven Triptolide to be a potent treatment for cancer. It has been scientifically established that Triptolide can wipe out a long list of cancers, including 7 types of prostate cancer1,2,3,23, two types of breast cancer3,4, stomach cancer5, ovarian cancer6, bone cancer7, uterus cancer8, two types of gallbladder cancer9, adrenal cancer10, thyroid cancer11, skin cancer12, two types of mouth cancer13, bone cancer, blood cancer, liver cancer14, and two highly-aggressive types of pancreatic cancer cells15. In another study that tested Triptolide on pancreatic cancer cells, significantly increased rates of cell death were achieved in just 24 hours following treatment16, and, in a study on breast cancer, a 60% reduction in cancer cells was observed just 72 hours after treatment17. Drug companies seeking new ways to profit fund studies that combine, for example, their toxic chemotherapy agent Sorafenib with medicines like Triptolide – a combination which was found to be very effective at causing cancer cell death, and because of the Triptolide’s beneficial effects, a much smaller dose of Sorafenib was needed, making treatment with chemotherapeutic agents less dangerous18. More on the subject of chemotherapy, Triptolide was found to have a “profound antitumor effect” on a type of bile duct cancer that was completely resistant to the effects of chemotherapy18. Outstandingly, the anti-cancer effects of Triptolide are achieved using “extremely low concentrations19,” reported one study, and these effects carried over to in vivo studies, where Triptolide inhibited tumor growth in mice with skin cancer, breast cancer, bladder cancer, stomach cancer20, and was found to shrink bile duct tumors in mice 75-80%, just one month after treatment21. Triptolide was also tested on human-simulated tumors, and researchers found that tumor growth and disease progression were inhibited22. Although it’s difficult to know for certain, one group of researchers claimed that Triptolide was a more potent destroyer of cancer cells than Celstrol23, and, in a study that used both Triptolide and Celastrol together, the combination “showed outstanding synergistic anticancer effect in vitro and in vivo24,” which could indicate that the use of a powdered root or whole-plant version of the Thunder God Vine for treating cancer might be a righteous choice.
- 1. In a 2015 study that was published in the journal Oncotarget, researchers demonstrated that Triptolide induced cell death in three different types of prostate cancer cells, and reduced tumor growth in prostate cancer mice. (Zhao, et al., 2015)
- 2. At Heilongjiang University of Chinese Medicine in 2007, the effects of various doses of Triptolide were evaluated on prostate cancer cells, and it was found that the drug induced apoptosis, thereby inhibiting the spread of prostate cancer in mice. (Zhang, et al., 2007)
- 3. Lu L. of Guangzhou Medical University in China led a study in 2011 that asked if Triptolide could induce apoptosis in human breast and prostate cancer cells. Investigators reported an increase in proteins associated with cell death induction inside both types of human cancer cells. (Lu, et al., 2011)
- 4. The aim of this Chinese study was to determine the effect of Triptolide on breast cancer cells. Published in Experimental and Therapeutic Medicine in 2014, “results of the present study indicate that Triptolide induces the apoptosis [or cell death] of breast cancer cells.” (Shao, et al., 2014)
- 5. Four scientists from China conducted a study in 2014, testing Triptolide on stomach cancer cells, and reported that “Triptolide induced significant apoptosis of gastric cancer cells in a dose-and time-dependent manner.” (Wang, et al., 2014)
- 6. In a study published in 2014 by Chinese researchers, it was found that “Triptolide selectively kills ovarian cancer cells” and study authors concluded that Triptolide is “a promising chemotherapeutic agent against a broad spectrum of ovarian carcinomas.” (Wu, et al., 2014)
- 7. Until December 2013, when this study was published in the Indian Journal of Biochemistry and Biophysics, the effects of Triptolide on bone cancer were unknown. This research established that Triptolide can induce cell death in human bone cancer cells “by activating both death receptor and mitochondrial apoptotic pathways.” (Kwon, et al., 2013)
- 8. Human uterus cancer cells and mice induced with human uterine cancer were treated with Triptolide in a study from 2015 published in the Asian Pacific Journal of Cancer Prevention. Research showed the extract significantly inhibited cancer cell growth and triggered apoptosis in both cultured human cancer cells and in tumor mice. (Ni, et al., 2015)
- 9. For the first time ever, the effects of Triptolide on gallbladder cancer cells were documented in a 2014 study published in the journal Molecules, where it was found that Triptolide “strongly suppressed colony formation” and induced apoptosis in two types of gallbladder cancer cells. “Triptolide may be a promising drug to treat gallbladder carcinoma,” proclaimed study authors. (Hu, et al., 2014)
- 10. Recognizing a need for research into Triptolide’s effects on human adrenal cancer cells, researchers out of China conducted a study in 2011 and published it in Oncology Reports. Their study revealed that Triptolide can induce apoptosis in human adrenal cancer cells. (Wu, et al., 2011)
- 11. Triptolide was used to treat human thyroid cancer cells in a Chinese study, published in 2009, and the results showed that Triptolide induced apoptosis in human thyroid cancer cells. (Zhu, et al., 2009)
- 12. The anti-tumor effect of Triptolide on human skin cancer cells in vitro was tested in a study from Changsha, China in 2009, where researchers watched the substance inhibit the spread of cancer and trigger cancer cell death. (Chen, et al., 2009)
- 13. In 2009, researchers from Taiwan published a study that demonstrated Triptolide can induce cell death in two types of mouth cancer cells. (Chen, et al., 2009)
- 14. This study, from The Hong Kong University of Science and Technology in 2001, tested the therapeutic value of Triptolide against three different types of cancer cells. Examiners found that Triptolide prevented the growth and induced the death of bone marrow cancer, blood cancer, and liver cancer cells. (Chan, et al., 2001)
- 15. In May 2015, V. Sangwan and colleagues from the University of Minnesota tested Thunder God Vine extract Triptolide on two aggressive pancreatic cancer cell-types in vitro and observed Triptolide induce apoptotic cell death in both of them. (Sangwan, et al., 2015)
- 16. In a study that was published in the World Journal of Gastroenterology in 2008, pancreatic cancer cells were treated with Triptolide and its ability to induce cancer cell death was examined. Triptolide was found to prevent the growth of the human pancreatic cancer cells, and just 24 hours after treatment, it caused significantly increased rates of cancer cell death. (Zhou, et al., 2008)
- 17. Junjie Li and his cohorts in China probed the efficacy of Triptolide in a 2014 study where they treated breast cancer cells and breast cancer stem cells both in vivo and in vitro. In just 72 hours, the team observed Triptolide eradicate 60% of breast cancer cells in the first cell-type, and 30% in the other. In the mice, “Triptolide treatment in vivo significantly inhibited tumor growth compared with mock treatment,” reported researchers. (Li, et al., 2014)
- 18. A study using Triptolide in combination with the chemotherapy drug Sorafenib, both in vivo and in vitro, was conducted in 2014 by a research group from Minnesota, and after treating liver cancer cells with Triptolide, Sorafenib, or a combination of both, the results showed that the combination of drugs caused cancer cell death more effectively than either drug alone. Their studies on mice were much more exciting, because they directly compared the tumor volume reductions resulting from treatment with either Sorafenib, Triptolide, Sorafenib & Triptolide, or salt water (for the control group). The results showed that after two weeks of treatment, while researchers witnessed 900% growth of tumors in the control mice, the Sorafenib decreased tumor growth by 59%, Triptolide decreased tumor growth by 84%, and a combination of Sorafenib & Triptolide decreased tumor growth by 93%. The combination of Sorafenib & Triptolide allowed for a much lower dose of chemotherapy drug Sorafenib to be used, less than 10% in fact, making the chemotherapy treatment less dangerous. (Alsaied, et al., 2014)
- 19. The limits of the fierce Thunder God Vine extract Triptolide were tested in 2014, when researchers from Nanjing, China used it to treat an extremely chemotherapy-resistant type of human bile duct cancer (in cell cultures and in mice) called Cholangiocarcinoma (CAA), known for its ability to evade cell death. “Triptolide has profound antitumor effect on CCA”, and “…would be a promising therapeutic agent for CCA,” concluded study (Ding, et al., 2014)
- 20. In 2003, a study from Georgetown University Medical Center in Washington, D.C. was conducted to assess the anti-tumor properties of Triptolide. In cultured cells, Triptolide “inhibited the proliferation and colony formation of tumor cells at extremely low concentrations,” and in mice treated for 2 to 3 weeks, investigators observed Triptolide inhibit tumor growth in four different types of cancerous tumors, including skin cancer, breast cancer, bladder cancer and stomach cancer. Researchers showed that Triptolide was effective even in cells that were resistant to chemotherapy, and asserted that the antitumor effect of Triptolide “was comparable or superior to that of conventional antitumor drugs, such as Adriamycin, mitomycin, and cisplatin.” (Yang, et al., 2003)
- 21. In 1998, Bangkok, Thailand, a group of researchers led by Tengchaisri T. showed that at very low doses, Triptolide was toxic to bile duct cancer cells, and inhibited tumor growth in hamsters. Remarkably, just one month after the initial treatment, the tumor mass of the treated group of mice had been reduced by 75 to 80%. (Tengchaisri, et al., 1998)
- 22. A study published in the International Journal of Cancer in 2014, tested Triptolide for its therapeutic effects on pancreatic cancer and found that in vivo, Triptolide inhibited tumor growth and halted disease progression. Researchers concluded that the treatment may be superior to current chemotherapeutic treatments. (Liu, et al., 2014)
- 23. Researchers demonstrated, in a 2012 study from China, that Triptolide inhibited cell growth and induced cell death in two different types of prostate cancer cells, and noted that its anti-cancer effect was superior to that of Celastrol. (Huang, et al., 2012)
- 24. Until this study in 2015, published in Oncotarget, the effects of Triptolide in combination with Celastrol had been unknown. When 16 researchers from China tested both of these substances together on mice with induced tumors, they discovered that Triptolide and Celastrol “significantly inhibited the growth of tumors without obvious toxicity” and “showed outstanding synergistic anticancer effect in vitro and in vivo.” (Jiang, et al., 2015)
TG, a rare substance from the Thunder God Vine that hasn’t been studied much, was shown to double the lifespan of mice with tumors of the liver, connective tissues, and in mice with both human and mouse breast cancers. TG also completely inhibited the development of lung cancer in mice injected with a poison commonly used by scientists to induce lung cancer1.
- TG, a compound first isolated from the Thunder God Vine in this 1992 study from Wuhan, China, was tested on four groups of mice bearing different types of tumors – liver, connective tissues, mouse breast cancer, and human breast cancer. The average lifespan of animals treated with TG was doubled compared to control mice. Researchers then injected mice with a poison used to induce lung cancer, and found that TG completely inhibited the cancer from developing. Also reported was that TG had “remarkable killing effect” on human blood and bone marrow cancer cells. (Xu, et al., 1992)
As spectacular as the therapeutic effects of Triptolide are, they are limited by its lack of solubility in water. Minnelide, a water-soluble prodrug of Triptolide, was synthesized in order to make Triptolide more bioavailable, and while the idea of utilizing a man-made medicine might not appeal to some, what’s important is that the genesis of a water-soluble form of Triptolide has actually improved its medical value. Minnelide has been shown to kill cancer cells in culture and in mice bearing pancreatic cancer tumors1,2,3, including one study, which found a 60% decrease in tumor volume4. Even in the rare and difficult-to-treat cancer malignant mesothelioma, Minnelide has shown to significantly reduce tumors5. Minnelide succeeded where chemotherapy failed in one study by eliminating chemotherapy-resistance that had been developed by cancer cells6, and perhaps the most amazing finding of all – Minnelide increased the blood flow into tumors by 400% by reducing the buildup of blood-vessel-constricting collagen7. Two of the ways Minnelide has been found to impart its healing effects are by down-regulating the expression of pro-survival genes (HSP70, BIRC5, BIRC4, BIRC2, UACA) and up-regulating expression of the pro-apoptic genes (APAF-1)12, and (p53)8, responsible for tumor suppression. Finally, Minnelide halted cancer progression in rats with blood cancer9, colon cancer10, ovarian cancer11, lung cancer12, and bone cancer13, at times nearly doubling their survival.
- 1. In a study from the University of Minnesota, Minneapolis in 2015, researchers examined the effect of Thunder God Vine extract Minnelide on pancreatic cancer stem cells. After inducing cancer in mice by injecting cancer stem cells under their skin, the Minnelide “resulted in the regression of tumors derived from these cells.” (Nomura, et al., 2015)
- 2. In January 2016, a study was published in the Journal of Gastrointestinal Surgery that explored the use of Minnelide on a novel form of pancreatic cancer in mice. After tumors were implanted into the mice, they were treated with Minnelide, and it was found that “Minnelide treatment resulted in a significant decrease in the tumor weight and volume.” (Majumder, et al., 2016)
- 3. Pancreatic cancer, one of the most lethal forms of cancer (with less than a 5% chance of survival after 5-years), was treated with Minnelide in a study by researchers from the University of Minnesota in 2012. The efficacy of Minnelide was tested in cultured cells and in three different mouse models, and the study reported that in all cases, “Minnelide was highly effective in reducing pancreatic tumor growth and spread, and improving survival.” (Chugh, et al., 2012)
- 4. After inducing cancer in two groups of mice and treating one with Minnelide, a study from the University of Minnesota found that, treatment of mice with Minnelide for pancreatic cancer resulted in “a 60% decrease in tumor volume compared with the untreated ones.” (Banerjee , et al., 2014)
- 5. A rare cancer that affects the protective tissues lining the abdomen and lungs called malignant mesothelioma is difficult to treat and in need of new forms of treatment, so researchers from the University of Minnesota tested both Triptolide and Minnelide on cell cultures, and they found that both substances significantly reduced cancer cell counts by inducing cancer cell death. In vivo, the researchers treated mice with Minnelide, after inducing mesothelioma tumors in them, and concluded that their tumors were significantly reduced in size. (Jacobson, et al., 2015)
- 6. Pancreatic cancer cells treated with chemotherapeutic agent Oxaliplatin eventually develop a resistance to the treatment and it no longer works. In this study from 2016, researchers found that by treating the aggressive Oxaliplatin-resistant cancer cells with Minnelide, the resistance was eliminated, and the two treatments together “inhibited tumor progression,” suggesting the combination of Minnelide and Oxaliplatin “has immense potential to emerge as a novel therapeutic strategy against pancreatic cancer.” (Modi, et al., 2016)
- 7. One of the greatest challenges with treating pancreatic cancer is the buildup of collagen inside the tumor, which compresses blood vessels and inhibits the flow of blood (and medicine contained within it) to where it is needed. This makes treatment extremely difficult and survival rates poor. A breakthrough study published in Clinical Cancer Research in 2016 by researchers from the University of Minnesota examined whether or not Minnelide would be effectively delivered despite this collagenous buildup. Following treatment of pancreatic cancer mice as well as xenografts of cancer tissue, the study found a reduction in the collagen that inhibited blood flow in both models, resulting in a 400% increase in functional vessels leading into the tumor. “In conclusion,” reported researchers, “these results are extremely promising as they indicate that Minnelide, along with having anticancer effects is also able to deplete stroma in pancreatic tumors, which makes it an effective therapy for pancreatic cancer.” (Banerjee , et al., 2016)
- 8. In the Journal of Oral Oncology in 2014, a study examined whether or not Minnelide could reactivate the function of the “p53” gene responsible for suppressing tumors. In these experiments, a number of skin cancer and cervical cancer cells were tested, as well as xenografts and mice bearing skin cancer tumors (some were HPV positive, and some were not). In every single model tested, both in vitro and in vivo, Minnelide reactivated the “p53” gene, which resulted in the halting of disease progression and cancer cell death. (Caicedo-granados, et al., 2014)
- 9. A study from 2015 included a group of scientists from Kansas, Georgia and Minneapolis in the United States, and another from Maharashtra, India. After injecting blood cancer cells into the tail veins of rats and treating them with Minnelide, they observed a reduction in leukemia and an overall increase in survival. (Ganguly, et al., 2015)
- 10. In 2015, the effects of Triptolide and Minnelide were evaluated against colon cancer in a study published in the journal Laboratory Investigation. Researchers found that Triptolide was effective at killing two types of colon cancer cells, Minnelide “markedly inhibited the growth of colon cancer” in tissue grafts, and almost doubled survival times in animals with colon cancer that had already spread to their liver. (Oliveira, et al., 2015)
- 11. A study was undertaken by researchers in 2014 to evaluate the effectiveness of Minnelide on ovarian cancer growth, in both cell cultures (in vitro) and in animal models (in vivo). In vitro, Minnelide effectively decreased two types of ovarian cancer cells, and in vivo, Minnelide increased the survival of mice bearing ovarian tumors. (Rivard, et al., 2014)
- 12. In 2013, anti-cancer activity of Minnelide was tested on cultured lung cancer cells and in mice with induced lung cancer. In both mice and in cell cultures it was found that the substance prevented cancer from proliferating and it induced cancer cell death by down-regulating expression of pro-survival genes (HSP70, BIRC5, BIRC4, BIRC2, UACA) and up-regulating expression of the pro-apoptic gene (APAF-1). (Rousalova, et al., 2013)
- 13. The therapeutic effects of Minnelide were tested on bone cancer in a study from the University of Minnesota in 2013. It was found that the substance “was effective in significantly inducing apoptosis in all osteosarcoma cell lines tested…” Treatment with Minnelide was also found to significantly reduce tumor burden and lung metastasis in two of the models tested. (Banerjee, et al., 2013)
Caspi O, Polak A. [Traditional immunosuppression–Lei Gong Teng in modern medicine]. Harefuah. 2013;152(7):404-9, 433.
Choi BS, Kim H, Lee HJ, et al. Celastrol from ‘Thunder God Vine’ protects SH-SY5Y cells through the preservation of mitochondrial function and inhibition of p38 MAPK in a rotenone model of Parkinson’s disease. Neurochem Res. 2014;39(1):84-96.
Lee JY, Lee BH, Kim ND, Lee JY. Celastrol blocks binding of lipopolysaccharides to a Toll-like receptor4/myeloid differentiation factor2 complex in a thiol-dependent manner. J Ethnopharmacol. 2015;172:254-60.
Liu J, Lee J, Salazar hernandez MA, Mazitschek R, Ozcan U. Treatment of obesity with celastrol. Cell. 2015;161(5):999-1011.
Park B. Triptolide, a diterpene, inhibits osteoclastogenesis, induced by RANKL signaling and human cancer cells. Biochimie. 2014;105:129-36.
Wang Y, Cao L, Xu LM, et al. Celastrol Ameliorates EAE Induction by Suppressing Pathogenic T Cell Responses in the Peripheral and Central Nervous Systems. J Neuroimmune Pharmacol. 2015;10(3):506-16.
Wan L, Liu J, Huang CB, et al. Xinfeng Capsule () for the treatment of rheumatoid arthritis patients with decreased pulmonary function – A randomized controlled clinical trial. Chin J Integr Med. 2016;22(3):168-76.
Yang L, Li Y, Ren J, et al. Celastrol attenuates inflammatory and neuropathic pain mediated by cannabinoid receptor type 2. Int J Mol Sci. 2014;15(8):13637-48.
Gofman, J. Lecture. Stinson Beach, California. 1999. Medical X-rays and Breast Cancer. Available: https://www.youtube.com/watch?v=AzW0zIjKcmE [February 24, 2016].
Luo Y, Pu X, Luo G, et al. Nitrogen-containing dihydro-β-agarofuran derivatives from Tripterygium wilfordii. J Nat Prod. 2014;77(7):1650-7.
1. Kim Y, Kang H, Jang SW, Ko J. Celastrol inhibits breast cancer cell invasion via suppression of NF-ĸB-mediated matrix metalloproteinase-9 expression. Cell Physiol Biochem. 2011;28(2):175-84.
2. Xu J, Wu CL, Huang J. Effect of celastrol in inhibiting metastasis of lung cancer cells by influencing Akt signaling pathway and expressing integrins. Zhongguo Zhong Yao Za Zhi. 2015;40(6):1129-33.
3. Xu J, Wu CL. Anti-metastasis of celastrol on esophageal cancer cells and its mechanism. Sheng Li Xue Bao. 2015;67(3):341-7.
4. Yu X, Zhou X, Fu C, et al. Celastrol induces apoptosis of human osteosarcoma cells via the mitochondrial apoptotic pathway. Oncol Rep. 2015;34(3):1129-36.
5. Li PP, He W, Yuan PF, Song SS, Lu JT, Wei W. Celastrol induces mitochondria-mediated apoptosis in hepatocellular carcinoma Bel-7402 cells. Am J Chin Med. 2015;43(1):137-48.
6. Fribley AM, Miller JR, Brownell AL, et al. Celastrol induces unfolded protein response-dependent cell death in head and neck cancer. Exp Cell Res. 2015;330(2):412-22.
7. Mou H, Zheng Y, Zhao P, Bao H, Fang W, Xu N. Celastrol induces apoptosis in non-small-cell lung cancer A549 cells through activation of mitochondria- and Fas/FasL-mediated pathways. Toxicol In Vitro. 2011;25(5):1027-32.
8. Idris AI, Libouban H, Nyangoga H, Landao-bassonga E, Chappard D, Ralston SH. Pharmacologic inhibitors of IkappaB kinase suppress growth and migration of mammary carcinosarcoma cells in vitro and prevent osteolytic bone metastasis in vivo. Mol Cancer Ther. 2009;8(8):2339-47.
9. Yu X, Zhou X, Fu C, et al. Celastrol induces apoptosis of human osteosarcoma cells via the mitochondrial apoptotic pathway. Oncol Rep. 2015;34(3):1129-36.
10. Mi C, Shi H, Ma J, Han LZ, Lee JJ, Jin X. Celastrol induces the apoptosis of breast cancer cells and inhibits their invasion via downregulation of MMP-9. Oncol Rep. 2014;32(6):2527-32.
11. Kannaiyan R, Manu KA, Chen L, et al. Celastrol inhibits tumor cell proliferation and promotes apoptosis through the activation of c-Jun N-terminal kinase and suppression of PI3 K/Akt signaling pathways. Apoptosis. 2011;16(10):1028-41.
12. Fan XX, Li N, Wu JL, et al. Celastrol induces apoptosis in gefitinib-resistant non-small cell lung cancer cells via caspases-dependent pathways and Hsp90 client protein degradation. Molecules. 2014;19(3):3508-22.
13. Lin L, Sun Y, Wang D, Zheng S, Zhang J, Zheng C. Celastrol Ameliorates Ulcerative Colitis-Related Colorectal Cancer in Mice via Suppressing Inflammatory Responses and Epithelial-Mesenchymal Transition. Front Pharmacol. 2015;6:320.
14. Rajendran P, Li F, Shanmugam MK, et al. Celastrol suppresses growth and induces apoptosis of human hepatocellular carcinoma through the modulation of STAT3/JAK2 signaling cascade in vitro and in vivo. Cancer Prev Res (Phila). 2012;5(4):631-43.
15. Han X, Sun S, Zhao M, et al. Celastrol stimulates hypoxia-inducible factor-1 activity in tumor cells by initiating the ROS/Akt/p70S6K signaling pathway and enhancing hypoxia-inducible factor-1α protein synthesis. PLoS ONE. 2014;9(11):e112470.
16. Lu L, Shi W, Deshmukh RR, et al. Tumor necrosis factor-α sensitizes breast cancer cells to natural products with proteasome-inhibitory activity leading to apoptosis. PLoS ONE. 2014;9(11):e113783.
17. Song J, Shi F, Zhang Z, et al. Formulation and evaluation of celastrol-loaded liposomes. Molecules. 2011;16(9):7880-92.
18. Sanna V, Chamcheu JC, Pala N, Mukhtar H, Sechi M, Siddiqui IA. Nanoencapsulation of natural triterpenoid celastrol for prostate cancer treatment. Int J Nanomedicine. 2015;10:6835-46.
19. Niemelä E, Desai D, Nkizinkiko Y, Eriksson JE, Rosenholm JM. Sugar-decorated mesoporous silica nanoparticles as delivery vehicles for the poorly soluble drug celastrol enables targeted induction of apoptosis in cancer cells. Eur J Pharm Biopharm. 2015;96:11-21.
1. Zhao F, Huang W, Zhang Z, et al. Triptolide induces protective autophagy through activation of the CaMKKβ-AMPK signaling pathway in prostate cancer cells. Oncotarget. 2015;
2. Zhang R, Zhang PY, Guo J, et al. Effects of triptolide on prostate carcinoma in mouse RM-1 cells. Zhonghua Nan Ke Xue. 2007;13(3):237-41.
3. Lu L, Kanwar J, Schmitt S, et al. Inhibition of tumor cellular proteasome activity by triptolide extracted from the Chinese medicinal plant ‘thunder god vine’. Anticancer Res. 2011;31(1):1-10.
4. Shao H, Ma J, Guo T, Hu R. Triptolide induces apoptosis of breast cancer cells via a mechanism associated with the Wnt/β-catenin signaling pathway. Exp Ther Med. 2014;8(2):505-508.
5. Wang BY, Cao J, Chen JW, Liu QY. Triptolide induces apoptosis of gastric cancer cells via inhibiting the overexpression of MDM2. Med Oncol. 2014;31(11):270.
6. Wu J, Li QQ, Zhou H, et al. Selective tumor cell killing by triptolide in p53 wild-type and p53 mutant ovarian carcinomas. Med Oncol. 2014;31(7):14.
7. Kwon HY, Kim KS, An HK, Moon HI, Kim HJ, Lee YC. Triptolide induces apoptosis through extrinsic and intrinsic pathways in human osteosarcoma U2OS cells. Indian J Biochem Biophys. 2013;50(6):485-91.
8. Ni J, Wu Q, Sun ZH, Zhong J, Cai Y, Huang XE. The Inhibition Effect of Triptolide on Human Endometrial Carcinoma Cell Line HEC-1B: a in vitro and in vivo Studies. Asian Pac J Cancer Prev. 2015;16(11):4571-6.
9. Hu YP, Tan ZJ, Wu XS, et al. Triptolide induces s phase arrest and apoptosis in gallbladder cancer cells. Molecules. 2014;19(2):2612-28.
10. Wu PP, Liu KC, Huang WW, et al. Triptolide induces apoptosis in human adrenal cancer NCI-H295 cells through a mitochondrial-dependent pathway. Oncol Rep. 2011;25(2):551-7.
11. Zhu W, Hu H, Qiu P, Yan G. Triptolide induces apoptosis in human anaplastic thyroid carcinoma cells by a p53-independent but NF-kappaB-related mechanism. Oncol Rep. 2009;22(6):1397-401.
12. Chen M, Tan S, Zhang G, et al. [Effect of triptolide on the proliferation and apoptosis of human epidermal squamous cell carcinoma cell line A431 in vitro]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2009;34(7):638-41.
13. Chen YW, Lin GJ, Chia WT, Lin CK, Chuang YP, Sytwu HK. Triptolide exerts anti-tumor effect on oral cancer and KB cells in vitro and in vivo. Oral Oncol. 2009;45(7):562-8.
14. Chan EW, Cheng SC, Sin FW, Xie Y. Triptolide induced cytotoxic effects on human promyelocytic leukemia, T cell lymphoma and human hepatocellular carcinoma cell lines. Toxicol Lett. 2001;122(1):81-7.
15. Sangwan V, Banerjee S, Jensen KM, et al. Primary and liver metastasis-derived cell lines from KrasG12D; Trp53R172H; Pdx-1 Cre animals undergo apoptosis in response to triptolide. Pancreas. 2015;44(4):583-9.
16. Zhou GX, Ding XL, Huang JF, et al. Apoptosis of human pancreatic cancer cells induced by Triptolide. World J Gastroenterol. 2008;14(10):1504-9.
17. Li J, Liu R, Yang Y, et al. Triptolide-induced in vitro and in vivo cytotoxicity in human breast cancer stem cells and primary breast cancer cells. Oncol Rep. 2014;31(5):2181-6.
18. Alsaied OA, Sangwan V, Banerjee S, et al. Sorafenib and triptolide as combination therapy for hepatocellular carcinoma. Surgery. 2014;156(2):270-9.
19. Ding X, Zhang B, Pei Q, et al. Triptolide induces apoptotic cell death of human cholangiocarcinoma cells through inhibition of myeloid cell leukemia-1. BMC Cancer. 2014;14:271.
20. Yang S, Chen J, Guo Z, et al. Triptolide inhibits the growth and metastasis of solid tumors. Mol Cancer Ther. 2003;2(1):65-72.
21. Tengchaisri T, Chawengkirttikul R, Rachaphaew N, Reutrakul V, Sangsuwan R, Sirisinha S. Antitumor activity of triptolide against cholangiocarcinoma growth in vitro and in hamsters. Cancer Lett. 1998;133(2):169-75.
22. Liu L, Salnikov AV, Bauer N, et al. Triptolide reverses hypoxia-induced epithelial-mesenchymal transition and stem-like features in pancreatic cancer by NF-κB downregulation. Int J Cancer. 2014;134(10):2489-503.
23. Huang W, He T, Chai C, et al. Triptolide inhibits the proliferation of prostate cancer cells and down-regulates SUMO-specific protease 1 expression. PLoS ONE. 2012;7(5):e37693.
24. Jiang QW, Cheng KJ, Mei XL, et al. Synergistic anticancer effects of triptolide and celastrol, two main compounds from thunder god vine. Oncotarget. 2015;6(32):32790-804.
1. Xu JY, Yang J, Li LZ. [Antitumor effect of Tripterygium wilfordii]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1992;12(3):161-4, 134.
1. Nomura A, Mcginn O, Dudeja V, Sangwan V, Saluja AK, Banerjee S. Minnelide effectively eliminates CD133(+) side population in pancreatic cancer. Mol Cancer. 2015;14:200.
2. Majumder K, Arora N, Modi S, et al. A Novel Immunocompetent Mouse Model of Pancreatic Cancer with Robust Stroma: a Valuable Tool for Preclinical Evaluation of New Therapies. J Gastrointest Surg. 2016;20(1):53-65.
3. Chugh R, Sangwan V, Patil SP, et al. A preclinical evaluation of Minnelide as a therapeutic agent against pancreatic cancer. Sci Transl Med. 2012;4(156):156ra139.
4. Banerjee S, Nomura A, Sangwan V, et al. CD133+ tumor initiating cells in a syngenic murine model of pancreatic cancer respond to Minnelide. Clin Cancer Res. 2014;20(9):2388-99.
5. Jacobson BA, Chen EZ, Tang S, et al. Triptolide and its prodrug minnelide suppress Hsp70 and inhibit in vivo growth in a xenograft model of mesothelioma. Genes Cancer. 2015;6(3-4):144-52.
6. Modi S, Kir D, Giri B, et al. Minnelide Overcomes Oxaliplatin Resistance by Downregulating the DNA Repair Pathway in Pancreatic Cancer. J Gastrointest Surg. 2016;20(1):13-24.
7. Banerjee S, Modi S, Mcginn O, et al. Impaired Synthesis of Stromal Components in Response to Minnelide Improves Vascular Function, Drug Delivery, and Survival in Pancreatic Cancer. Clin Cancer Res. 2016;22(2):415-25.
8. Caicedo-granados E, Lin R, Fujisawa C, Yueh B, Sangwan V, Saluja A. Wild-type p53 reactivation by small-molecule Minnelide™ in human papillomavirus (HPV)-positive head and neck squamous cell carcinoma. Oral Oncol. 2014;50(12):1149-56.
9. Ganguly S, Home T, Yacoub A, et al. Targeting HSF1 disrupts HSP90 chaperone function in chronic lymphocytic leukemia. Oncotarget. 2015;6(31):31767-79.
10. Oliveira AR, Beyer G, Chugh R, et al. Triptolide abrogates growth of colon cancer and induces cell cycle arrest by inhibiting transcriptional activation of E2F. Lab Invest. 2015;95(6):648-59.
11. Rivard C, Geller M, Schnettler E, et al. Inhibition of epithelial ovarian cancer by Minnelide, a water-soluble pro-drug. Gynecol Oncol. 2014;135(2):318-24.
12. Rousalova I, Banerjee S, Sangwan V, et al. Minnelide: a novel therapeutic that promotes apoptosis in non-small cell lung carcinoma in vivo. PLoS ONE. 2013;8(10):e77411.
13. Banerjee S, Thayanithy V, Sangwan V, Mackenzie TN, Saluja AK, Subramanian S. Minnelide reduces tumor burden in preclinical models of osteosarcoma. Cancer Lett. 2013;335(2):412-20.