Bitter Melon Extract and Homeopathic Remedies Inhibit Growth of Breast Cancer Cells

February 23, 2010 — Research has resulted in new and evolving therapies for breast cancer, and advances have changed the paradigm of patient care. There is also emerging research into novel and less toxic therapies. Although still very early science, 2 studies that investigate therapies that fall under the umbrella of integrative or complementary therapy have demonstrated promising results in breast cancer.

In a study published in the March issue of Cancer Research, investigators found that the extract of bitter melon exerts a significant effect against breast cancer cell growth. The results of the study suggest that bitter melon extract is able to modulate several signal-transduction pathways, resulting in a significant decrease in cell proliferation and induced apoptosis. These results, note the authors, indicate that bitter melon extract could be used as a chemopreventive agent. The second trial, published in the February issue of the International Journal of Oncology, demonstrated that certain homeopathic remedies exerted preferential cytotoxic effects against 2 lines of breast cancer cells. These effects ultimately led to the delay and/or arrest of cell cycles and to apoptosis.

We were quite impressed to find that homeopathic remedies have similar effects to chemotherapy. The authors note that, in the laboratory setting, the cytotoxic effect of 2 of the homeopathic remedies evaluated in this study, Carcinosin and Phytolacca, were similar to the activity of paclitaxel (Taxol). "We felt that homeopathy needed to be tested in the same way that we test new chemotherapeutic drugs," said lead author Moshe Frenkel, MD, founder and former medical director of the Integrative Medicine Program at the University of Texas M.D. Anderson Cancer Center in Houston, in a statement. "We were quite impressed to find that homeopathic remedies have similar effects to chemotherapy on breast cancer cells but without affecting normal cells, a very exciting finding." Bitter Melon Extract

Bitter melon (Momordica charantia) has been used as a remedy for diabetes in places such as India, China, and Central America. It is widely cultivated in Asia, Africa, and South America, and is eaten as a vegetable in India and China, explained lead author Ratna B. Ray, PhD, professor in the Department of Pathology at Saint Louis University in Missouri. Preparations of bitter melon extract from independent laboratories have been shown to have a beneficial effect on glucose metabolism, plasma, and hepatic lipids. Charantin (a steroid glycoside) and polypeptide-p or plant insulin (a 166-residue insulin mimetic peptide) are believed to contribute to bitter melon's hypoglycemic activity, according to the authors. In addition, bitter melon contains additional glycosides, including mormordin, vitamin C, carotenoids, flavanoids, and polyphenols. In this experimental study, Dr. Ray and colleagues examined the efficacy of bitter melon extract as an anticancer agent, using human breast cancer cells (MCF-7 and MDA-MB-231) and primary human mammary epithelial cells as an in vitro model. The effect of bitter melon was evaluated in both estrogen-receptor (ER)-positive and ER-negative breast cancer cells. They found that apoptosis of breast cancer cells was accompanied by increased poly(ADP-ribose) polymerase cleavage and caspase activation. Treatment of cancer cells with bitter melon extract inhibited the expression of survivin and claspin, which are proteins involved in the inhibition of cell growth, the induction of apoptosis, and the regulation of the cell cycle, write the authors. Survivin is also involved in resistance to chemotherapy.

Treatment with bitter melon extract also enhanced p53, p21, and pChk1/2, and inhibited cyclin B1 and cyclin D1 expression, which suggests an additional mechanism of action that involves regulating the cell cycle, they note.

More studies are needed to better understand the molecular targets and the chemopreventive efficacy of bitter melon extract. "We are planning to do a preclinical trial," Dr. Ray told Medscape Oncology. "In fact, we are waiting for funding from [the National Institutes of Health]," he added.

Cytotoxic Effect of Homeopathic Remedies

In the second study, researchers from the M.D. Anderson Cancer Center evaluated the anticancer effect of 4 ultradiluted homeopathic remedies (Carcinosin, Phytolacca, Conium, and Thuja) against 2 human breast adenocarcinoma cell lines (MCF-7 and MDA-MB-231) and a cell line derived from immortalized normal human mammary epithelial cells.

Dr. Frenkel told Medscape Oncology that although his team has not investigated homeopathic remedies in other types of cancer cell lines, another researcher at M.D. Anderson evaluated the effect of homeopathic remedies on glioblastoma with a positive response. The researchers found that the homeopathic remedy Ruta graveolens selectively induced death in glioblastoma multiforme cells while promoting the proliferation of normal peripheral blood lymphocytes (Int J Oncol. 2003;23:975-982).

Approximately 10 years ago, researchers at the National Cancer Institute (NCI) evaluated a cancer treatment protocol that was developed at the P. Banerji Homeopathic Research Foundation (PBHRF) in Kolkata, India. The NCI researchers reviewed the cases of 10 patients with various cancers who were treated with the Banerji protocol. After rigorous evaluation, they confirmed partial responses in 4 of the patients with lung and esophageal cancers.

The study authors also point out that between 1990 and 2005, 941 patients with breast cancer were treated at the PBHRF with the Banerji protocol. Physicians at the clinic reported that tumors completely regressed in 19% of these patients, whereas in 21% of these patients they showed improvement or stabilized.

In their in vitro study, Dr. Frenkel and his team tried to determine the effectiveness of the Banerji protocol on breast cancer cell lines.

Their findings showed that these homeopathic remedies exerted "preferential cytotoxic effects" against the human breast carcinoma cell lines MCF-7 and MDA-MB-231. These effects appeared to result from an alteration in the expression of cell-cycle regulatory proteins, which caused cell-cycle delay/arrest and the induction of cell death by activation of the apoptotic cascade.

More studies are needed to investigate these remedies as preventive and/or therapeutic treatments for breast cancer. "We can move to animal studies that use those remedies and consider moving into clinical trials with patients who refuse conventional treatment, patients for whom conventional care did not work, or patients who suffer from side effects to the extent that they cannot take any other treatments," said Dr. Frenkel.

The authors of the Cancer Research study was funded by Blue Ribbon and Doisy research funds from Saint Louis University. The International Journal of Oncology study was wholly supported by internal funds from the M.D. Anderson Cancer Center. The researchers have disclosed no relevant financial relationships.

Cancer Res. 2010;70;1925-1931.
Int J Oncol. 2010;36:395-403. Abstract

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