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Brefeldin A inhibits colorectal cancer growth by triggering Bip/Akt‐regulated autophagy
Author(s) -
Zhou Li,
Gao Wei,
Wang Kui,
Huang Zhao,
Zhang Lu,
Zhang Zhe,
Zhou Jing,
Nice Edouard C.,
Huang Canhua
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201801983r
Subject(s) - autophagy , brefeldin a , protein kinase b , colorectal cancer , cancer research , pi3k/akt/mtor pathway , microbiology and biotechnology , chemistry , medicine , cancer , biology , signal transduction , apoptosis , golgi apparatus , biochemistry , endoplasmic reticulum
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. FASEB J. 33, 5520–5534 (2019). www.fasebj.org