A bioactive compound of the neem plant, a plant widely used in traditional Asian medicine, may be a promising treatment for prostate cancer, according to the results of a recent animal study.
The study, “Nimbolide-Induced Oxidative Stress Abrogates STAT3 Signaling Cascade and Inhibits Tumor Growth in Transgenic Adenocarcinoma of Mouse Prostate Model,” published in Antioxidants and Redox Signaling, shows that the compound, called nimbolide, can decrease prostate tumor size by up to 70 percent and cut tumor spread by half.
Although prostate cancer is one of the most commonly diagnosed cancers worldwide, available therapies for metastatic prostate cancer are only marginally effective, and new treatment alternatives are needed to improve patient outcomes.
“Although the diverse anti-cancer effects of nimbolide have been reported in different cancer types, its potential effects on prostate cancer initiation and progression have not been demonstrated in scientific studies,” associate professor Gautam Sethi, with the Department of Pharmacology at the Yong Loo Lin School of Medicine at the National University of Singapore, and study’s lead researcher, said in a press release.
Recent studies had shown that both neem extracts and nimbolide could impair the proliferation and induce the death of prostate cancer cells. The researchers hypothesized that nimbolide was exerting such effects by targeting the oncogenic STAT3 pathway, which is highly activated in prostate cancer cells and critical for their proliferation and survival. STAT3 is also involved in the mechanism of resistance to androgen-deprivation therapies.
“In this research, we have demonstrated that nimbolide can inhibit tumor cell viability — a cellular process that directly affects the ability of a cell to proliferate, grow, divide, or repair damaged cell components — and induce programmed cell death in prostate cancer cells,” said Sethi.
When mouse models of prostate cancer were given nimbulide orally for 12 weeks, the researchers found that prostate cancer size was reduced by up to 70 percent, compared to non-treated mice. Metastasis formation in both the lung and liver were also reduced by half.
In addition, investigators also found that nimbolide could prevent the formation of pre-malignant lesions, as well as the progression from pre-malignant to malignant lesions.
“This is possible because a direct target of nimbolide in prostate cancer is glutathione reductase, an enzyme which is responsible for maintaining the antioxidant system that regulates the STAT3 gene in the body,” Sethi said. “We have found that nimbolide can substantially inhibit STAT3 activation and thereby abrogating the growth and metastasis of prostate tumor.”
Although the mice treated with nimbolide did not exhibit any significant adverse effects, the research team in hoping to conduct genetic and proteomic studies to examine potential side effects of the compound, as well as to determine if nimbolide acts on other molecular targets.
They also expect to assess whether nimbolide can be combined with approved drugs for prostate cancer, such as Taxotere (docetaxel) and Xtandi (enzalutamide).