TY - JOUR
T1 - Brefeldin A inhibits colorectal cancer growth by triggering Bip/Akt-regulated autophagy
AU - Zhou, Li
AU - Gao, Wei
AU - Wang, Kui
AU - Huang, Zhao
AU - Zhang, Lu
AU - Zhang, Zhe
AU - Zhou, Jing
AU - Nice, Edouard C.
AU - Huang, Canhua
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
KW - autophagic flux
KW - cancer therapy
KW - ER stress
UR - http://www.scopus.com/inward/record.url?scp=85064125352&partnerID=8YFLogxK
U2 - 10.1096/fj.201801983R
DO - 10.1096/fj.201801983R
M3 - Article
C2 - 30668917
AN - SCOPUS:85064125352
SN - 0892-6638
VL - 33
SP - 5520
EP - 5534
JO - The FASEB Journal
JF - The FASEB Journal
IS - 4
ER -
