A shrub found in Southeast Asia can give you a rash like poison ivy; but it may also stop prostate cancer.
The croton plant, long known to oriental herbalists and homeopaths as a purgative, has an oil in its seeds that shows promise for the treatment of prostate cancer – the second leading cause of cancer death in men in the United States. The active ingredient in the oil is 12-O-tetradecanoylphorbol-13-acetate, a compound generally known as TPA.
The finding was reported in the March 1, 2004, issue of Cancer Research by Xi Zheng, Allan Conney and other scientists at the Susan Lehman Cullman Laboratory for Cancer Research at Rutgers, The State University of New Jersey, and the Cancer Institute of New Jersey (CINJ).
"We demonstrated that TPA could simultaneously stop the growth of new prostate cancer cells, kill existing cancer cells and ultimately shrink prostate tumors," said Conney, the William M. and Myrle W. Garbe Professor of Cancer and Leukemia Research at Rutgers' Ernest Mario School of Pharmacy, and a member of CINJ.
In addition to studies on the effect of TPA alone, the researchers also tested TPA in combination with all-trans retinoic acid (ATRA), a vitamin A derivative previously shown to be effective in treating leukemia.
"We knew that ATRA is an effective synergist with TPA in treating leukemia cells in the laboratory, but prostate cancer is a different situation, probably involving different molecular mechanisms," Conney said.
The studies by Zheng and Conney are the first to show an impressive synergy between TPA and ATRA in inhibiting the growth of cultured prostate cancer cells and the first to assess their combined effects, and the effects of TPA alone, on human tumors grown in mice.
Scientists, intrigued by the skin-irritating property of croton seed oil, demonstrated more than 50 years ago that croton oil and its constituent TPA promoted tumors in laboratory animals following the introduction of a strong carcinogen at a low dose. Subsequent laboratory tests, however, produced dramatically different outcomes.
"It turned out that extremely low concentrations of TPA had an extraordinarily potent effect on myeloid leukemia cells, causing them to revert to normal cell behavior," Conney explained.
However, it was a long time before anyone acknowledged that TPA could actually do good things for people, Conney observed.
Investigators at China's Henan Tumor Research Institute and Rutgers, interested in the potential beneficial effects of TPA, began a collaborative study in 1995. When TPA was administered to terminally ill myeloid leukemia patients in China, the number of leukemia cells in the blood and bone marrow decreased and there were remissions of the disease.
"We are clearly encouraged by our laboratory results with TPA and ATRA on prostate cancer cells," Conney said. "Our studies are an important early step in a long process, and we are planning additional testing in humans. Further research with these compounds and others could provide hope for the half million new cases of prostate cancer each year."