Resveratrol induces cell death through ROS‑dependent downregulation of Notch1/PTEN/Akt signaling in ovarian cancer cells

Molecular Medicine Reports
Thae Hyun KimJae Suk Woo

Abstract

Resveratrol, a natural polyphenol compound, has been reported to exert anticancer activity in various cancer cells. The present study investigated the effect and underlying mechanisms of resveratrol in the human ovarian cancer cell lines, A2780 and SKOV3. Treatment with resveratrol induced apoptotic cell death in dose‑ and time‑dependent manners, as well as a transient increase of reactive oxygen species (ROS) generation. Resveratrol‑induced cell death was attenuated by the antioxidant, N‑acetylcysteine (NAC), suggesting that ROS were involved in the observed cell death. Treatment with resveratrol resulted in a ROS‑dependent decrease of Notch1 signaling. When cells were transfected to overexpress Notch1 using EF.hlCN1.CMV.GFP, resveratrol‑induced cell death was blocked. Western blot analysis demonstrated that resveratrol also upregulated phospho‑phosphatase and tensin homolog (p‑PTEN) and downregulated phospho‑Akt (p‑Akt). Overexpression of p‑Akt by transfection with a constitutively active form (caAkt), and the p‑PTEN inhibitor SF1670 prevented resveratrol‑induced cell death. The caspase‑3 inhibitor z‑DEVD‑FMK significantly attenuated the resveratrol‑induced caspase‑3 cleavage. Taken together, the results of the present study ...Continue Reading

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Citations

Mar 22, 2020·International Journal of Molecular Sciences·Abdullah ShaitoGianfranco Pintus
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bo LiYi Charlie Chen

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