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
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.
View Figures
View References

Related Articles

Journal Cover

April 2012
Volume 40 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
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