The croton plant, long known to oriental herbalists and homeopaths as a purgative, is a shrub native to Southeast Asia that can irritate the skin. But the seed oil also contains the active ingredient 12-O-tetradecanoylphorbol-13-acetate, a compound generally known as TPA.
"We demonstrated that TPA could simultaneously stop the growth of new prostate cancer cells, kill existing cancer cells and ultimately shrink prostate tumors," said Allan Conney, professor of Cancer and Leukemia Research at Rutgers University in the US.
Earlier detection and wide use of hormone treatment have significantly reduced death rates from prostate cancer over the last 10 years in North America and Western Europe. But it remains the most common type of cancer found in American and European men, and only causes less cancer deaths among men than lung cancer.
Conney and colleagues studied TPA in combination with all-trans retinoic acid (ATRA), a vitamin A derivative previously shown to be effective in treating leukaemia.
"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.
For the study, published in the 1 March issue of Cancer Research (64,1811-1820), mice in which the researchers had grown human prostate tumors received either TPA, ATRA or a combination of the two once a day for 46 days. After 21 days of treatment, 31 per cent of the ATRA group showed some tumor remission, compared to 62 per cent of the TPA group. But those receiving both TPA and ATRA saw a 100 per cent regression.
Treatment with TPA or the combination continued to inhibit tumor growth for the duration of the study, but mice receiving ATRA alone did not see tumor growth slow beyond 28 days of daily injections.
Commenting on the results 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."
Croton oil and its constituent TPA was first investigated more than 50 years ago, but it was not until 1995 when investigators at China's Henan Tumor Research Institute and Rutgers began a collaborative study to look at TPA's effects on people. When the chemical 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.