Natural Therapies Research
Thanks to the generous support of the Panda Charitable Foundation, current nature-derived compounds being studied by our researchers include:
Baicalein is a compound found in a Chinese herb called Huang Qin (also known as baikal scullcap). John Yim
, M.D., associate professor and surgeon, Division of Surgical Oncology, has found that this compound enhances the activity of IRF-1, a protein that suppresses tumor growth by triggering cancer cells’ self-destruction mechanism and makes them more vulnerable to immune responses. Laboratory studies showed that this compound exhibited no toxicity, making it a promising compound for therapy. In animal trials, baicalein — when combined with common chemotherapy drug cisplatin — has been found to be particularly potent against breast, endometrial, liver, lung, ovarian and prostate cancers.
Yim is currently investigating to see how baicalein and cisplatin work together to fight these tumors. This will be particularly beneficial for cancer patients who are resistant to cisplatin-only therapy (such as some subtypes of ovarian cancers) or patients who cannot tolerate high-dose chemotherapy due to its toxicity (as baicalein could lower chemotherapy doses needed to treat cancer).
Yim and his team hope to begin the first in-human trials for this treatment by the end of 2017.
He has also combined baicalein and metformin, a completely safe anti-diabetic drug in clinical trials for it's anti-cancer effect, and found very strong synergy. Additionally, Yim has found success when combining SR4, another City of Hope drug in development.
He is also exploring the efficacy of baicalein in lung cancer, and this has led to interesting findings. In animal tests, baicalein was found to significantly suppress lung cancer tumors.
Berbamine is derived from the European barberry, an edible berry which has been used in traditional medicine to treat a variety of infections and conditions. Of the barberry’s numerous compounds, berbamine in particular has been shown to exhibit anti-cancer properties and City of Hope researchers Wendong Huang
, Ph.D., professor, Department of Diabetes Complications & Metabolism Research; and David Horne
, Ph.D., vice provost and associate director, Beckman Research Institute of City of Hope, have been experimenting with berbamine derivatives to develop a cancer drug. To date, they have found several derivatives that have greater anti-cancer potency compared to unaltered berbamine. Additionally, these derivatives have relatively low toxicity, making these compounds promising for a number of cancers.
Huang, Horne and their team are currently conducting further preclinical studies on berbamine derivatives in preparation for a human trial application.
“Triple-negative” breast cancers — which makes up 10 to 15 percent of all breast cancer diagnoses — are particularly hard to treat because the cancerous cells lack the three receptors that are targeted by commonly available therapies (estrogen, progesterone and HER2). Shiuan Chen
, Ph.D., professor and chair, Department of Cancer Biology, and his colleagues found that blueberry extract slowed down the growth and proliferation of triple negative breast cancer cells. Further, the extract also inhibits the cancer cells’ ability to migrate to other organs and metastasize.
Chen and his team are currently investigating the compounds and pathways responsible for this action. Once identified and isolated, this can then be further evaluated in preclinical studies.
Cancer and Diet
Current cancer treatment with drugs completely overlooks the impact of diet composition on cancer treatment outcomes. Research from Shiuan Chen, Ph.D., professor and chair, Department of Cancer Biology, has found that many drugs will modulate how cancer cells utilize nutrients, such as proteins, carbohydrates and fats. mTOR is a key factor that regulates food intake, a nutrient sensor and a major target for cancer treatment. Dr. Chen and his team are studying the best diets for successful cancer treatment outcomes using mTOR inhibitors. They are currently studying the impact of high protein diets on ER+ and triple negative breast cancer, and in animal studies, have found that a high protein diets may decrease tumor growth.
Cancer cells exploit a protein called VEGF to grow new blood vessels to fuel their growth and spread, a process called angiogenesis. In laboratory studies, Wei Wen
, Ph.D., assistant research professor, Surgical Oncology, has found that cinnamon extract can inhibit VEGF activity by binding to one of its receptors, VEGFR2. That, in turn, prevents angiogenesis. Although there are several anti-angiogenesis drugs in clinical use, toxicity and side effects can limit its use. A compound derived from cinnamon may be safer and more effective, so Wen and her colleagues are continuing their studies into this spice’s potential as a cancer fighting agent.
Epipolythiodioxopiperazines — or ETPs — are small molecules produced by fungi. ETPs’ unique molecular structures give them potential as anti-cancer agents, so David Horne, Ph.D., vice provost and associate director, Beckman Research Institute of City of Hope, and his colleagues are synthesizing ETP derivatives in hopes of developing an extremely potent compound against tumors. Such compounds would target histone methyl transferases, enzymes that play a role in the development of many cancers.
In animal trials, Horne's team has found success in reducing the tumor burden of acute myeloid leukemia tumors with a novel ETP called NT1721. Treatment with NT1721 also significantly increased survival times in these studies.
Horne has also found potent anticancer activity in other ETP compounds in pancreatic cancer tumors.
Grape Seed Extract
Research conducted by Shiuan Chen, Ph.D., professor and chair, Department of Cancer Biology, has demonstrated that chemicals in grape seed extract — found in grape skin and seeds and even red wine — can suppress the production of estrogen, which fuels the growth of hormone-sensitive breast cancers.
Additionally, Wei Wen, Ph.D., assistant research professor, surgical oncology, and her colleagues found that grape seed extract also lowers the level of a protein called HIF-1a. Cells need HIF-1a to make VEGF, a protein required to grow new blood vessels in a process called angiogenesis. Blocking HIF-1a, and in turn VEGF, could potentially block the tumor’s blood supply, starving it of needed nutrients.
The researchers hope to build on their findings and study grape seed extract’s anti-cancer effects in combination with other therapies.
Grape Skin Extract
, Ph.D., Billy and Audrey L. Wilder Professor in Tumor Immunotherapy, has found that reservatrol, a compound derived from red grape skins, may have potential in activating the estrogen receptor of breast cancer cells, thereby making them sensitive to hormone-targeted therapies. In previous studies, Yu and her colleagues showed that the protein STAT3 is responsible for the silenced estrogen receptor in triple-negative breast cancers. More recently in a published paper, they found that resveratrol may be able to stop and reverse this effect of STAT3, showing its potential in overcoming breast cancer’s resistance to hormone therapy.
Yu and her team are currently evaluating resveratrol and its mechanisms to further understand how this compound works in order to develop a safe and effective treatment for patients with hormone-resistant breast cancers.
Studies conducted by Shiuan Chen, Ph.D., professor and chair, Department of Cancer Biology, and Przemyslaw Twardowski, M.D., and their colleagues are investigating the role of mushrooms in preventing breast and prostate cancer recurrences. Previous studies by Chen have shown that mushroom extracts can block aromatase and 5-alpha reductase, enzymes needed for hormone production (which consequently fuels the growth of hormone-sensitive cancers.)
Based on these findings, Palomares and Twardowski have conducted clinical trials to see the effect of mushrooms on hormone levels, cancer recurrence and overall health among breast and prostate cancer survivors. Based on the findings from these trials, Chen, Twardowski and their team can then further develop mushroom extracts as a useful tool to help prevent prostate and breast cancer relapses after initial treatment.
In a separate investigation, Marianna Koczywas
, M.D., clinical professor, Department of Medical Oncology & Therapeutics Research, is studying a compound derived from shitake mushrooms called MM-10-001 against lung cancer. Previous studies have shown that MM-10-001 can stimulate the immune system, and Koczywas is conducting a phase I clinical trial to see if this compound can trigger an anti-cancer immune response for lung cancer patients.
Shiuan Chen, Ph.D., professor and chair, Department of Cancer Biology, and his colleagues have found that pomegranates contain six compounds that may prevent breast cancer growth. These substances work by blocking aromatase, the same enzyme that Chen found is blocked by mushroom powder. Of the six pomegranate compounds, one called urolithin B has the most powerful effect. In lab tests, Chen and his team found that urolithin B could stop the growth of estrogen-responsive breast cancer cells, suggesting that pomegranate intake may be a viable strategy for blocking breast cancer growth.
Studies at City of Hope showed that the Chinese herbal medicine xinfeng may hold promise in preventing or treating lung cancer based on its ability to suppress inflammation.
Inflammation is often linked to the development of cancer and autoimmune diseases, and Binghui Shen
, Ph.D., chair and professor, Department of Cancer Genetics and Epigenetics, has found that the enzyme MMP9 is aggressively expressed in mice with inflamed lungs. In an effort to see how this process can be thwarted, Shen and his team found that xinfeng is effective in suppressing MMP9 levels. Based on these findings, Shen is investigating to see whether MMP9 can be a biomarker for lung cancer development in humans and if xinfeng can be used to help prevent or treat lung cancer.
In another study, Dan Raz
, M.D., co-director, Lung Cancer and Thoracic Oncology Program
, is looking to see if xinfeng can prevent lung cancer recurrence. Like Shen, Raz seeks to target inflammation and is currently using animal models to determine who would be most likely to benefit from treatment with xinfeng, alone or when combined with chemotherapy. Based on these findings, Raz and his colleagues hope to start a human trial utilizing this herb-based drug.