Breast cancer is a blanket term used to describe a variety of diseases, each with markedly different treatment options and prognosis for survival. In particular, ER/PR/HER2 triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer, which accounts for 15–25% of breast tumors. Given the state of research and prognosis of TNBC, there is a great need for novel therapeutics among the most promising are treatments derived from Cucurbitacins, which have been previously proposed to act as potential anti-tumor drugs.

Accumulated evidence suggests that Cucurbitacin E (CuE) is a potential novel anti-cancer drug. To date, it has not thoroughly investigated the efficacy and functional mechanisms of CuE on TNBC. Dr. Ceshi Chen from KIZ and Dr. Minghua Qiu from KIB’s lab extracted 12 different compounds and found that administration of CuE resulted in marked anti-cancer activities in several lines of cancerous cells, then we focused on triple negative breast cancer lines. Specifically, the IC50 of CuE was about 10–70 nM in five TNBC cell lines. Among them, MAD-MB-468 and SW527 are the most sensitive TNBC cell lines. CuE significantly decreased cell viability, induced cell cycle G2/M phase arrest, and trigged apoptosis in both MAD-MB-468 and SW527 cell lines. CuE decreased the protein levels of CyclinD1, XIAP, Survivin, Bcl-2, and Mcl-1, significantly increased the activation of JNK and inhibited the activation of AKT and ERK. These results suggest that CuE may be a viable compound for developing novel TNBC therapeutics.

This project is funded by Natural Science Foundation of China (NSFC).(http://www.ncbi.nlm.nih.gov/pubmed/25072848)