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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1020-1028
Number of pages9
JournalInternational journal of oncology
Volume40
Issue number4
DOIs
Publication statusPublished - Apr 1 2012

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Autophagy
Colonic Neoplasms
Reactive Oxygen Species
Apoptosis
Caspase 3
Light
Stilbenes
HT29 Cells
Caspase Inhibitors
Microtubule-Associated Proteins
Caspase 8
Annexin A5
Vitis
Polyphenols
Growth
Vacuoles
Fluorescein
Immunoblotting
Cysteine
resveratrol

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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.

In: International journal of oncology, Vol. 40, No. 4, 01.04.2012, p. 1020-1028.

Research output: Contribution to journalArticle

Miki, Hisanori ; Uehara, Norihisa ; Kimura, Ayako ; Sasaki, Tomo ; Yuri, Takashi ; Yoshizawa, Katsuhiko ; Tsubura, Airo. / Resveratrol induces apoptosis via ROS-triggered autophagy in human colon cancer cells. In: International journal of oncology. 2012 ; Vol. 40, No. 4. pp. 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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