Furowanin A-induced autophagy alleviates apoptosis and promotes cell cycle arrest via inactivation STAT3/Mcl-1 axis in colorectal cancer

Aim Furowanin A (Fur A) is a flavonoid isolated from Millettia pachycarpa Benth. Studies show its potent anti-neoplastic effects against leukemia cells. The aim of the present study was to determine the potential therapeutic effect of Fur A against colorectal Cancer (CRC), and elucidate the underlying mechanism.

Material and methods: Cell Counting Kit-8 (CCK-8) assay was used to determine cell, and TUNEL and Annexin-V/PI staining was used to detect Apoptosis and the cell cycle distribution. The expression levels of specific proteins in the CRC cells were analyzed by Western blotting. A xenograft model was also established to evaluate the therapeutic effect of Fur A in vivo.

Key findings: Fur A suppressed proliferation, blocked cell cycle progression, induced Apoptosis and promoted Autophagy in CRC cells. Interestingly, Fur A-induced Autophagy functioned not only as a survival mechanism against Apoptosis but also intensified the cell cycle arrest in CRC cells. In addition, Fur A mediated its effects via the inactivation of the STAT3/Mcl-1 axis.

Significance: Fur A is a promising drug candidate for the treatment and prevention of CRC.

Apoptosis; Autophagy; Cell cycle arrest; Colorectal cancer; Furowanin A; STAT3.