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
  • View Affiliations

  • 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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Copy and paste a formatted citation
APA
Miki, H., Uehara, N., Kimura, A., Sasaki, T., Yuri, T., Yoshizawa, K., & Tsubura, A. (2012). Resveratrol induces apoptosis via ROS-triggered autophagy in human colon cancer cells. International Journal of Oncology, 40, 1020-1028. https://doi.org/10.3892/ijo.2012.1325
MLA
Miki, H., Uehara, N., Kimura, A., Sasaki, T., Yuri, T., Yoshizawa, K., Tsubura, A."Resveratrol induces apoptosis via ROS-triggered autophagy in human colon cancer cells". International Journal of Oncology 40.4 (2012): 1020-1028.
Chicago
Miki, H., Uehara, N., Kimura, A., Sasaki, T., Yuri, T., Yoshizawa, K., Tsubura, A."Resveratrol induces apoptosis via ROS-triggered autophagy in human colon cancer cells". International Journal of Oncology 40, no. 4 (2012): 1020-1028. https://doi.org/10.3892/ijo.2012.1325