A new study led by Yale University in the US found that an ancient four-herb Chinese herbal remedy first described 1,800 years ago reduced gastrointestinal toxicity and boosted the antitumor effect of the chemotherapy drug CPT-11 (irinotecan) in mice with colon cancer.

A paper on the study was published in the journal Science Translational Medicine on 18 August.

Senior author Dr Yung-Chi "Tommy" Cheng, Henry Bronson professor of pharmacology at Yale and co-director of the University Cancer Center's Developmental Therapeutics, co-discovered the formula, known as PHY906. He and Yale have a financial interest in the company that is developing it.

Cheng told the press that:

"Chemotherapy causes great distress for millions of patients, but PHY906 has multiple biologically active compounds which can act on multiple sources of discomfort."

PHY906 comprises four herbs and is based on a herbal recipe that in China is known as Huang Qin Tang that was originally used to treat nausea, vomiting and diarrhea as far back as 1,800 years ago. Chang and colleagues decided to investigate its ability to reduce the gastrointestinal effects of a common chemotherapy drug without affecting its ability to kill cancer cells.

The researchers found that after giving PHY906 to mice with colon cancer that were undergoing chemotherapy with CPT-11 the animals experienced less toxicity, lost less weight and showed more anti-tumor activity than similar mice not given the formula. The formula had also encouraged the growth of new intestinal stem cells.

"PHY906 did not protect against the initial DNA damage and apoptosis triggered by CPT-11 in the intestine, but by 4 days after CPT-11 treatment, PHY906 had restored the intestinal epithelium by promoting the regeneration of intestinal progenitor or stem cells and several Wnt signaling components," they wrote.

PHY906 appeared to reduce inflammation in the mice by "decreasing the infiltration of neutrophils or macrophages", as well as reducing the expression of a tumor necrosis factor in the intestine, and "proinflammatory cytokine concentrations in plasma".

In a further experiment they showed that PHY906 also stimulated the activity of a particular Wnt protein (Wnt3a) in human embryonic kidney-293 cells.

Wnt proteins are a large family of cell-to-cell signalling molecules important to embryo development and whose disruption is known to lead to cancer.

The researchers concluded that the "herbal medicine PHY906 can counteract the toxicity of CPT-11 via several mechanisms that act simultaneously".

Cheng said:

"This combination of chemotherapy and herbs represents a marriage of Western and Eastern approaches to the treatment of cancer."

However, in an accompanying editorial, "Are Herbal Medicines Ripe for the Cancer Clinic?", Dr Cathy Eng, of the Department of Gastrointestinal Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston, warns that a number of challenges have to be overcome before the formula can be used in humans.

When considering the use of complementary and alternative medicine (CAM) in the treatment of cancer patients, she wrote:

" ... one must take into account reproducibility of preclinical findings in clinical practice, quality assurance of herbal products, and potential toxicities associated with alternative therapies."

Funds from the National Cancer Institute of the National Institutes of Health (NIH) paid for the study.

"The Four-Herb Chinese Medicine PHY906 Reduces Chemotherapy-Induced Gastrointestinal Toxicity."
Wing Lam, Scott Bussom, Fulan Guan, Zaoli Jiang, Wei Zhang, Elizabeth A. Gullen, Shwu-Huey Liu and Yung-Chi Cheng.
Science Translational Medicine 18 August 2010: Vol. 2, Issue 45, p. 45ra59
DOI: 10.1126/scitranslmed.3001270

Additional source: Yale University.

Written by: Catharine Paddock, PhD