Brefeldin A inhibits colorectal cancer growth by triggering Bip/Akt-regulated autophagy

Colorectal Cancer (CRC) is one of the most prevalent neoplastic diseases worldwide, and effective treatment remains a challenge. Here, we found that the macrolide Antibiotic brefeldin A (BFA) exhibits considerable antitumor activity both in vitro and in vivo. Induction of complete autophagic flux is characterized as a key event in BFA-induced CRC suppression. Mechanistically, BFA provokes endoplasmic reticulum stress-mediated binding immunoglobulin protein (Bip) expression, leading to increased Bip/Akt interaction and resultant decreased Akt phosphorylation, thereby activating Autophagy. Autophagy inhibition or Bip suppression relieves BFA-induced cell death, suggesting a key role for Bip-regulated Autophagy in the antitumor properties of BFA. Moreover, BFA acts synergistically with paclitaxel or 5-fluorouracil in CRC suppression. Collectively, our study provides an important molecular basis for BFA-induced Autophagy and suggests that the Antibiotic BFA could be repositioned as a potential Anticancer drug for CRC treatment.-Zhou, L., Gao, W., Wang, K., Huang, Z., Zhang, L., Zhang, Z., Zhou, J., Nice, E. C., Huang, C. Brefeldin A inhibits colorectal Cancer growth by triggering Bip/Akt-regulated Autophagy.