Natural Prenylated Xanthones as Potential Inhibitors of PI3k/Akt/mTOR Pathway in Triple Negative Breast Cancer Cells.

Three prenylated xanthones, garcinone E (1: ), bannaxanthone D (2: ) and bannanxanthone E (3: ) were isolated from the leaves of Garcinia mckeaniana Graib. Their structures were elucidated by spectral methods and compared with literature data. To evaluate their anti-proliferative effects in tumor cells, firstly, cisplatin was used as a positive control and the effects of compound 1:  - 3: were determined by performing MTT assay in MDA-MB-231, CNE-2 and A549 cancer cells. The results showed compound 1:  - 3: exhibited stronger inhibitory effect than cisplatin in MDA-MB-231. Further effects of compound 1:  - 3: in TNBC MDA-MB-231 and MDA-MB-468 cells were examined by performing cell cycle and apoptosis assays. The results indicated that compound 1:  - 3: had ability to arrest cell cycle at G2/M phase and induce apoptosis. Furthermore, compound 2: significantly down-regulated PI3K, Akt and mTOR levels in both total proteins and phosphorylated form, which is its potential anti-cancer mechanism. These findings indicated that those prenylated xanthones might serve as promising leading compounds for the development of anticancer drug for TNBC.