Abstract 910: Genistein does not alter the effectiveness of taxane chemotherapeutics on human prostate cancer cells

Abstract

Abstract Prostate cancer (PCa) continues to be a major health problem in the United States. Despite the general effectiveness of androgen deprivation therapy, nearly all cases will progress to become resistant to this first-line treatment. The standard of care for castrate-resistant prostate cancer (CRPC) includes a regimen of chemotherapy with taxane-based agents. Patients with CRPC commonly make dietary modifications and/or use nutritional supplements in addition to their standard of care therapy. Soy products are commonly used by men with PCa, but there are only few publications addressing either the safety or efficacy of soy products in combination with chemotherapy. Previously published studies (Prostate 2013;73:1681-9) suggest that the soy isoflavone genistein has synergistic activity when combined the taxane drug cabazitaxel. We studied the effects of the combination of taxane chemotherapy with genistein. PC-3, 22Rv1, and C4-2 prostate cancer cells were treated with genistein (1, 10, and 100 μM) in combination with docetaxel or cabazitaxel (0.1, 1.0, and 10.0 nM); after 72 hours proliferation was measured using the SRB assay and combination index (CI) analysis was performed to identify synergistic or antagonistic activity. Similar dose response curves were observed for docetaxel and cabazitaxel as expected since both drugs have the same mechanism of action. Compared to cells treated only with taxanes (either docetaxel or cabazitaxel), treatment with physiologically relevant concentrations genistein (1 μM and 10 μM) did not yield additional inhibition or enhancement of proliferation in any of the cell lines studied. There was slight synergistic activity at 100 μM in combination with 1 nM docetaxel in C4-2 (CI = 0.03), PC-3 (CI = 0.60), and 22Rv1 (CI = 0.20) cells. Similarly, slight synergism with 1 nM cabazitaxel was observed in all cell lines: C4-2 (CI = 0.29), PC-3 (CI = 0.40), and 22Rv1 (CI = 0.53). We did not observe any antagonism at clinically relevant concentration combinations of genistein and taxanes. These findings suggest that genistein supplementation is not harmful for PCa patients undergoing chemotherapy, but do not fully support findings of others that demonstrate synergistic activity. Although we did observe an enhancement of growth inhibition, it only occurred at the highest concentration of genistein (100 μM) tested, which is beyond what is achievable through dietary consumption of soy products. Quantities of genistein consumed in the diet or by supplementation are likely not sufficient to enhance the cytotoxicity of chemotherapy, but can be used without reducing the effectiveness of taxane drugs. Citation Format: Jillian N. Eskra, Alaina Dodge, Maarten C. Bosland. Genistein does not alter the effectiveness of taxane chemotherapeutics on human prostate cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 910. doi:10.1158/1538-7445.AM2015-910