Resveratrol induces apoptosis via ROS-triggered autophagy in human colon cancer cells

Miki,Hisanori; Uehara,Norihisa; Kimura,Ayako; Sasaki,Tomo; Yuri,Takashi; Yoshizawa,Katsuhiko; Tsubura,Airo

doi:10.3892/ijo.2012.1325

Resveratrol induces apoptosis via ROS-triggered autophagy in human colon cancer cells

Authors:
- Hisanori Miki
- Norihisa Uehara
- Ayako Kimura
- Tomo Sasaki
- Takashi Yuri
- Katsuhiko Yoshizawa
- Airo Tsubura
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Affiliations: Department of Pathology II, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan
Published online on: January 3, 2012 https://doi.org/10.3892/ijo.2012.1325
Pages: 1020-1028

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Abstract

Resveratrol (Res; 3,4',5-trihydroxy-trans-stilbene), which is a polyphenol found in grapes, can block cell proliferation and induce growth arrest and/or cell death in several types of cancer cells. However, the precise mechanisms by which Res exerts anticancer effects remain poorly understood. Res blocked both anchorage-dependent and -independent growth of HT-29 and COLO 201 human colon cancer cells in a dose- and time-dependent manner. Annexin V staining and Western blot analysis revealed that Res induced apoptosis accompanied by an increase in Caspase-8 and Caspase-3 cleavage. In HT-29 cells, Res caused autophagy as characterized by the appearance of autophagic vacuoles by electron microscopy and elevation of microtubule-associated protein 1 light chain 3 (LC3)-II by immunoblotting, which was associated with the punctuate pattern of LC3 detected by fluorescein microscopy. Inhibition of Res-induced autophagy by the autophagy inhibitor 3-methyladenine caused a significant decrease in apoptosis accompanied by decreased cleavage of Casapse-8 and Caspase-3, indicating that Res-induced autophagy was cytotoxic. However, inhibition of Res-induced apoptosis by the pan-caspase inhibitor Z-VAD(OMe)-FMK did not decrease autophagy but elevated LC3-II levels. Interestingly, Res increased the intracellular reactive oxygen species (ROS) level, which correlated to the induction of Casapse-8 and Caspase-3 cleavage and the elevation of LC3-II; treatment with ROS scavenger N-acetyl cysteine diminished this effect. Therefore, the effect of Res on the induction of apoptosis via autophagy is mediated through ROS in human colon cancer cells.

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