Breast cancer is the most common malignant cancer diagnosed in women worldwide each year. Triple-negative breast cancers (TNBC), defined by the lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), account for approximately 15% of breast cancers. Moreover, TNBC is usually more aggressive and metastatic with a worse prognosis. Bitter melon (Momordica charantia) is well known as a dietary supplement. Recently, we have shown an anti-cancer activity of bitter melon extract (BME) in breast cancer mouse models, although the mechanism is poorly understood. Furthermore, we became interested to understand the role of BME on cholesterol and lipid metabolism in TNBC. Our mass spectrometry data suggested that stored as a cholesteryl esters (CE) in Lipid droplets (LD) were much lower in BME treated TNBC cells. We found that not only CE but also LD was reduced in BME treated TNBC cells. The acyl-CoA:cholesterol acyl transferase-1 (ACAT-1) catalyzes the formation of CE from free cholesterols together with long-chain fatty acyl coenzyme A. Therefore, inhibition of ACAT-1 resulted in downregulation of CE, and upregulation free cholesterols. The attenuated CE is known to reduce cancer proliferation. Subsequent study demonstrated that BME treatment highly inhibited ACAT-1 in TNBC cells. The upregulated free cholesterol negatively regulates sterol regulatory element-binding proteins (SREBPs), which regulates lipogenesis protein such as fatty acid synthase (FASN) associated with cancer cell proliferation. We also observed that SREBP-1 and -2 were barely detectable, and FASN and low-density lipoprotein receptor (LDLR) were reduced in BME treated TNBC cells as compared to control cells. To our knowledge, this is the first report demonstrating that BME suppresses TNBC cell growth through ACAT-1 inhibition. BME supplement may potentially be an additional regimen in human breast cancer treatment.

Citation Format: So Hee Shim, Robert Steele, Ratna Ray. Bitter melon extract suppresses triple-negative breast cancer growth by inhibiting ACAT1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3532.