Oleanolic acid arrests cell cycle and induces apoptosis via ROS‐mediated mitochondrial depolarization and lysosomal membrane permeabilization in human pancreatic cancer cells

Journal of Applied Toxicology - Tập 33 Số 8 - Trang 756-765 - 2013
Jianteng Wei1,2, Ming Liu2, Haizhou Liu2, Hui Wang1,2, Fengxia Wang3, Yuyan Zhang4, Lijun Han2, Xiukun Lin5,2
1Graduate University, Chinese Academy of Sciences, Beijing 100049, China
2Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
3School of Pharmacy, Shandong University, Jinan, Shandong, China
4College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China
5Department of Pharmacology, Capital Medical University, Beijing 100069, China

Tóm tắt

ABSTRACTOleanolic acid (OA), a pentacyclic triterpenoid, exhibits potential anti‐tumor activity against many tumor cell lines. This study aims to examine the anti‐tumor activity of OA on pancreatic cancer cells and its potential molecular mechanism. The results showed that the proliferation of Panc‐28 cells was inhibited by OA in a concentration‐dependent manner, with an IC50 (The half maximal inhibitory concentration) value of 46.35 µg ml−1, as determined by MTT (3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay. The cell cycle was arrested in S phase and G2/M phase by OA. The study also showed that OA could induce remarkable apoptosis, evidenced by an increased percentage of early/late apoptotic cells, DNA ladder and nuclear morphology change. Further study revealed that OA could induce Reactive Oxygen Species (ROS) generation, mitochondrial depolarization, release of cytochrome C, lysosomal membrane permeabilization and leakage of cathepin B. The expression of apoptosis‐correlated proteins was also affected in cells treated with OA, including activation of caspases‐3/9 and cleavage of PARP. Further study confirmed that ROS scavenger vitamin C could reverse the apoptosis induced by OA in Panc‐28 cells. Our results provide evidence that OA arrests the cell cycle and induces apoptosis, possibly via ROS‐mediated mitochondrial and a lysosomal pathway in Panc‐28 cells. Copyright © 2012 John Wiley & Sons, Ltd.

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Journal of Applied Toxicology

Tập 33 Số 8

756-765

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