1. Academic Validation
  2. Brefeldin A inhibits colorectal cancer growth by triggering Bip/Akt-regulated autophagy

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

  • FASEB J. 2019 Apr;33(4):5520-5534. doi: 10.1096/fj.201801983R.
Li Zhou 1 2 3 Wei Gao 1 2 3 Kui Wang 1 2 Zhao Huang 1 Lu Zhang 1 Zhe Zhang 1 Jing Zhou 1 Edouard C Nice 4 Canhua Huang 1 2 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • 2 West China School of Basic Sciences and Forensic Medicine, Sichuan University, Chengdu, China.
  • 3 Department of Oncology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China.
  • 4 Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
Abstract

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.

Keywords

ER stress; autophagic flux; cancer therapy.

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