Abstract 5587: Bitter melon (Momordica charantia) extract suppresses adrenocortical cancer cell proliferation and growth through modulation of the cell cycle pathway and steroidogenic activity

Abstract

Abstract Malignant adrenal tumors or adrenocortical carcinomas are relatively rare; however, this form of cancer is highly malignant and presents with extremely poor prognosis as a consequence of metastasis or local invasion at the time of diagnosis. One of the approaches to control cancer progression and reduce cancer risk is prevention through diet. Bitter melon is widely consumed as a vegetable and especially as a traditional medicine in China, India, Japan, and Taiwan. In this study, we have used human and mouse adrenocortical cancer cells, H295R and Y1, respectively, as an in vitro model to assess the efficacy of bitter melon extract (BME) as an anticancer agent. First, we find that BME treatment of adrenocortical cancer cells results in a significant dose-dependent decrease in cell proliferation and growth. We also find that bitter melon extract has stronger anti-proliferation effect than blueberry extract on adrenocortical cancer cells. As expected, extracts from Acorn squash and Zucchini, two vegetables from the same Family of Cucurbitaceae as bitter melon, do not decrease cell proliferation in adrenocortical cancer cells. Second, apoptosis of adrenocortical cancer cells is accompanied by increased caspase activation and poly(ADP-ribose) polymerase cleavage. Further studies reveal that BME treatment enhances p53, p21, Mdm2, and ATF3 and inhibits cyclin D1, cyclin D2, cycline D3, mTOR, and JNK expression, suggesting an additional mechanism involving cell cycle regulation, cell motility, cell survival, and cell differentiation. Third, BME treatment also decreases steroidogenic activities in adrenocortical cancer cells by Western blotting and reporter gene assay. BME treatment of adrenocortical cancer cells results in a significant dose-dependent decrease in levels of NR5A1/SF1, MC2R, StAR proteins. Interestingly, we find that BME treatment decreases the level of phospho-CDK7, which is required, at least in part, for NR5A1/SF1 activation. Taken together, these data illustrate that inhibitory effect of bitter melon on the growth and proliferation of adrenocortical cancer cells through modulation of the cell cycle regulation and steroidogenic pathways. Therefore, BME can be used as a dietary supplement for prevention of adrenocortical cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5587. doi:10.1158/1538-7445.AM2011-5587