Phytochemicals

Prostate cancer is one of the leading causes of death in men aged 40-55. Genistein isoflavone (4', 5', 7-trihydroxyisoflavone) is a dietary phytochemical with demonstrated anti-tumor activities in a variety of cancers. Topotecan Hydrochloride (Hycamtin) is an FDA-approved chemotherapy drug, primarily used for secondary treatment of ovarian,cervical and small cell lung cancers. This study was to demonstrate the potential anticancer activities and synergy of topotecan-genistein combination in LNCaP prostate cancer cells. The potential efficacy and mechanism of topotecan/genistein-induced cell death was investigated... Results: The overall data indicated that i) both genistein and topotecan induce cellular death in LNCaP cells, ii) topotecan-genistein combination was significantly more efficacious in reducing LNCaP cell viabiligy compared to either genistein or topotecan alone, iii) in all cases, cell death was primarily through apoptosis, via the activation of the intrinsic pathway, iv) ROS levels were increased and VEGF expression was diminished significantly with the topotecan-genistein combination treatment, v) genetic analysis of topotecan-genistein treatment groups showed changes in genetic expression levels in pathway specific apoptotic genes.... Conclusion: Treatments involving topotecan-genistein combination may prove to be an attractive alternative phytotherapy of adjuvant therapy for prostate cancer.

This study investigated potential apoptotic and anti-proliferative effects of the phytochemicals, genistein and anthocyanin extract, as single and combined treatments in MCF-7 human breast cancer cells. Cells were exposed to single and combined treatments with the phytochemiclas for 48 and 72 hours. Cell viability was assessed using the MTT bioassay. Apoptosis induction was assessed using acridine orange ethidium bromide and rhodamine 123 ethidium bromide fluorescence assays. Both singe and combination treatments induced dose- and time-dependent apoptotic cell death in MCF-7 cells. The percentage of apoptosis was higher in combination treatments than single treatments with either phytochemical, although the difference was not statistically significant. The combination of genistein and anthocyanin extract peaked in efficacy at 48 hours of treatment, to exhibit significantly greater (P<. O5) dose- and time-dependent cell cytotoxicity than single treatments. This study reveals potential chemopreventive implications for the complementary effects of genistein and anthocyanin extract.

Prostate cancer is the most common form of non-skin cancer and the second leading cause of cancer deaths within the United States. The five year survival rate has increased from 69% to 99% over the last 25 years for the local and regional disease, but has remained fairly low (approximately 34%) for the advanced disease. Therefore, current research is aimed at finding complementary or alternative treatments that will specifically target components of the signal transduction, cell-cycle and apoptosis pathways to induce cell death, with little or no toxic side effects to the patient. In this study we investigated the effect of genistein on expression levels of genes involved in these pathways. Genistein is a (4 , 5 , 7-trihydroxyisoflavone) is a major isoflavone constituent of soy that has been shown to inhibit growth proliferation and induce apoptosis in cancer cells. The mechanism of genistein-induced cell death and potential molecular targets for genistein in LNCaP prostate cancer c ells was investigated using several techniques. The chemosensitivity of genistein towards the prostate cancer cells was investigated using the ATP and MTS assays and apoptosis induction was determined using apoptosis and caspase assays. Several molecular targets were also identified using cDNA microarray and RT-PCR analysis. Our results revealed that genistein induces cell death in a time and dose-dependent manner and regulates expression levels of several genes involved in carcinogenesis and immunogenicity. Several cell cycle genes were down-regulated, including the mitotic kinesins, cyclins and cyclin dependent kinases, indicating that genistein is able to halt cell cycle progression through the regulation of genes involved in this process.