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

Li Zhou, Wei Gao, Kui Wang, Zhao Huang, Lu Zhang, Zhe Zhang, Jing Zhou, Edouard C. Nice, Canhua Huang

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)5520-5534
Number of pages15
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume33
Issue number4
DOIs
Publication statusPublished - 1 Apr 2019

Keywords

  • autophagic flux
  • cancer therapy
  • ER stress

Cite this

Zhou, Li ; Gao, Wei ; Wang, Kui ; Huang, Zhao ; Zhang, Lu ; Zhang, Zhe ; Zhou, Jing ; Nice, Edouard C. ; Huang, Canhua. / Brefeldin A inhibits colorectal cancer growth by triggering Bip/Akt-regulated autophagy. In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019 ; Vol. 33, No. 4. pp. 5520-5534.
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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.",
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Brefeldin A inhibits colorectal cancer growth by triggering Bip/Akt-regulated autophagy. / Zhou, Li; Gao, Wei; Wang, Kui; Huang, Zhao; Zhang, Lu; Zhang, Zhe; Zhou, Jing; Nice, Edouard C.; Huang, Canhua.

In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 33, No. 4, 01.04.2019, p. 5520-5534.

Research output: Contribution to journalArticleResearchpeer-review

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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.

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