ReferenceID 3865

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

FASEB J

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 antitu

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Record Fields

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Reference Id
3865
Evidence Id
20455
Core Evidence Id
20455
Source Reference Id
1015
Herb2 Reference Id
HBREF001736
Subject Paper Key
HBIN018821_30668917
Pubmed Id
30668917
Doi
10.1096/fj.201801983R
Paper Title
Brefeldin A inhibits colorectal cancer growth by triggering Bip/Akt-regulated autophagy
Paper 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.
Journal
FASEB J
Publish Year
2019
Experiment Subject
Experiment Type
Others
Phenotype Related
Paper Title Cn
Paper Title En
Brefeldin A inhibits colorectal cancer growth by triggering Bip/Akt-regulated autophagy
Bilingual Status
semi_complete