Piperlongumine induces autophagy in biliary cancer cells via reactive oxygen species-activated Erk signaling pathway

Chen,San‑Yuan; Huang,Hsin‑Yi; Lin,Han‑Pei; Fang,Chiung‑Yao

doi:10.3892/ijmm.2019.4324

Piperlongumine induces autophagy in biliary cancer cells via reactive oxygen species-activated Erk signaling pathway

Authors:
- San‑Yuan Chen
- Hsin‑Yi Huang
- Han‑Pei Lin
- Chiung‑Yao Fang
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Affiliations: Department of Chinese Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 600, Taiwan, R.O.C., Department of Medical Research, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 600, Taiwan, R.O.C.
Published online on: August 23, 2019 https://doi.org/10.3892/ijmm.2019.4324
Pages: 1687-1696
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Biliary cancer (BC) is an aggressive neoplasm with high mortality. BC can be categorized into three groups: Intrahepatic cholangiocarcinoma (CCA; also known as bile duct cancer), extrahepatic cholangiocarcinoma and gallbladder cancer. Due to its heterogeneity and aggressiveness, the response to current chemotherapy and radiotherapy methods in patients with BC is poor. Therefore, there is an urgent requirement to develop drugs to treat BC. Piperlongumine (PL), a naturally occurring small molecule isolated from Piper longum L., exhibits anticancer activity by inducing reactive oxygen species (ROS) production. In the present study, the effects of PL on cell proliferation, cell cycle, apoptosis and autophagy in BC cells were investigated. PL induced BC cell death in a concentration‑ and time‑dependent manner by inducing ROS production. PL induced cell cycle arrest in CCA cells (HuCCT‑1) and gallbladder cancer cells (OCUG‑1) cells, but with distinct cell cycle distribution profiles. PL caused G2/M cell cycle arrest in HuCCT‑1 cells, and G0/G1 cell cycle arrest in OCUG‑1 cells. PL induced apoptosis and autophagy; PL treatment induced accumulation of LC3‑II in a concentration‑ and time‑dependent manner. The Erk signaling pathway appeared to be involved in autophagy induction. Application of the ROS scavenger, N‑acetyl‑l‑cysteine, to BC cells attenuated the cell death, cell cycle arrest, apoptosis and autophagy induced by PL treatment. These findings indicated that PL may be a potential agent for BC treatment in the future.

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