Ampelopsin‑induced reactive oxygen species enhance the apoptosis of colon cancer cells by activating endoplasmic reticulum stress‑mediated AMPK/MAPK/XAF1 signaling

Park,Ga  Bin; Jeong,Jee‑Yeong; Kim,Daejin

doi:10.3892/ol.2017.7255

Ampelopsin‑induced reactive oxygen species enhance the apoptosis of colon cancer cells by activating endoplasmic reticulum stress‑mediated AMPK/MAPK/XAF1 signaling

Authors:
- Ga Bin Park
- Jee‑Yeong Jeong
- Daejin Kim
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Affiliations: Department of Biochemistry, Kosin University College of Medicine, Busan 49267, Republic of Korea, Department of Anatomy, Inje University College of Medicine, Busan 47392, Republic of Korea
Published online on: October 23, 2017 https://doi.org/10.3892/ol.2017.7255
Pages: 7947-7956

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Abstract

Ampelopsin (Amp) is bioactive natural product and exerts anti‑cancer effects against several cancer types. The present study investigated the anti‑colon cancer activity of Amp and explored its mechanism of action. The treatment of colon cancer cells with Amp resulted in the dose‑ and time‑dependent induction of apoptosis via the activation of endoplasmic reticulum (ER) stress, 5' adenosine monophosphate‑activated protein kinase (AMPK), and c‑Jun N‑terminal protein kinase (JNK)/p38 mitogen‑activated protein kinases (MAPKs). Salubrinal, an ER stress inhibitor, prevented the upregulation of ER stress‑associated proteins, including phosphorylated protein kinase RNA‑like ER kinase, phosphorylated eukaryotic translation initiation factor 2α, glucose‑regulated protein 78, and CCAAT/enhancer‑binding protein homologous protein, as well as suppressing AMPK activation and the MAPK signaling pathway. Knockdown of AMPK by RNA interference failed to block ER stress. Additionally, SP600125 (a JNK inhibitor) and SB203580 (a p38‑MAPK inhibitor) effectively inhibited apoptosis and attenuated the expression of X‑linked IAP‑associated factor 1 (XAF1) and apoptotic Bcl‑2 family proteins (BCL2 antagonist/killer 1 and BCL2‑associated X protein) in Amp‑treated colon cancer cells. Furthermore, reactive oxygen species (ROS)‑mediated ER stress/AMPK apoptotic signaling pathway in Amp‑treated colon cancer cells were markedly inhibited by treatment with N‑acetyl‑L‑cysteine, a ROS scavenger. These results demonstrate that treatment with Amp induces the apoptotic death of colon cancer cells through ER stress‑initiated AMPK/MAPK/XAF1 signaling. These results also provide experimental information for developing Amp as therapeutic drug against colon cancer.

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