Abstract B38: A novel (+)-dehydroabietylamine derivative shows activity against triple-negative breast cancer cells

Abstract

Abstract In both well developed and developing countries, breast cancer remains the leading cause of cancer-related death among women. Very few effective treatments are available to its subtype triple negative breast cancer (TNBC), being unresponsive to estrogen therapy. A phenotypic screening was performed on terrestrial natural products against the human breast carcinoma cell lines MDA-MB-231, MA11, and MCF-7 targeting new chemical scaffolds to TNBC. Further studies were focused on abietanes natural products that preferentially inhibited proliferation of triple-negative MDA-MB-231 cells over estrogen receptor–positive cells. The activity of the abietane carnosol prompted to generate a focus library from the readily available (+)-dehydroabietylamine. The lead compound (+)-pentafluoro sulfonamide derivative of dehydroabietylamine displayed a promising EC50 of 9.0 μM against MDA-MB-231 and our mechanistic studies indicate it induced apoptosis, which was associated with activation of caspase-9 and -3 and the cleavage of PARP. Current progress towards this promising therapeutic area will be discussed. Citation Format: Lekh Nath Sharma Gautam, Taotao Ling, Fatima Rivas. A novel (+)-dehydroabietylamine derivative shows activity against triple-negative breast cancer cells. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B38.