Preprint Article Version 1 This version is not peer-reviewed

Mitochondrial Dysfunction and Cytochrome C Translocation Induced by Resveratrol Are Dependent on NF-κB Activity and Facilitate TRAIL Sensitivity in Human Lung Cancers

Version 1 : Received: 6 April 2018 / Approved: 6 April 2018 / Online: 6 April 2018 (18:59:41 CEST)
Version 2 : Received: 11 August 2018 / Approved: 13 August 2018 / Online: 13 August 2018 (06:18:03 CEST)

A peer-reviewed article of this Preprint also exists.

Rasheduzzaman, M.; Jeong, J.K.; Park, S.Y. Resveratrol sensitizes lung cancer cell to TRAIL by p53 independent and suppression of Akt/NF-κB signaling. Life Sciences 2018, 208, 208-220. Rasheduzzaman, M.; Jeong, J.K.; Park, S.Y. Resveratrol sensitizes lung cancer cell to TRAIL by p53 independent and suppression of Akt/NF-κB signaling. Life Sciences 2018, 208, 208-220.

Journal reference: Life Sciences 2018
DOI: 10.1016/j.lfs.2018.07.035.

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent that has the potential to sensitize a wide variety of cancer or transformed cells by inducing apoptosis. However, resistance to TRAIL is a growing concern, but it can be mitigated by employing different combination therapies. Resveratrol is a polyphenolic compound annex the outpouring of p53 and its pro-apoptotic modulator PUMA. Here, we showed the p53-independent activation of apoptosis by decrease the expression of phosphorylated Akt-mediated suppression of NF-κB activation that is also substantiated with the downregulation of anti-apoptotic factors Bcl-2 and Bcl-xl in Non-Small Cell lung adenocarcinoma cells (NSCLC), resulting in an attenuation of TRAIL resistance in combined treatment. Furthermore, apoptosis was induced in TRAIL-resistant lung cancer cells via a co-treatment of resveratrol and TRAIL, which was assessed by the loss of mitochondrial membrane potential, resulting in the translocation of cytochrome c from the mitochondria into the cytosol due to mitochondrial dysfunction. Moreover, autophagy flux was not affected by resveratrol-induced TRAIL-mediated apoptosis of lung cancer cells. Overall, targeting the NF-κB (p65) pathway via resveratrol attenuates TRAIL resistance and induces TRAIL-mediated apoptosis which could be the eminent therapeutic strategy to treat lung cancer.

Subject Areas

Resveratrol; autophagy; TRAIL; apoptosis; lung cancer cells; NF-κB; Cytochrome c

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