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Title: Bacoapside-1 induces mitochondrial fission and mitophagy to target arecoline-induced inflammasome activation in oral squamous cell carcinoma.
Authors: Mishra, Soumya Ranjan
Bhutia, Sujit K.
Keywords: Arecoline
NLRP3 inflammasome
Issue Date: Oct-2022
Citation: 10th International Symposium on Autophagy at Sapporo, Japan during 23rd-27th October 2022.
Abstract: Consumption of areca nut is a major contributor of oral cancer in India and arecoline is the major alkaloid present in it. In this study, we have investigated the role of arecoline in mitochondrial dysfunction and propose Bacopaside-I (BS-I), a saponin from Bacopa monnieri, to target the harmful effect of arecoline for oral cancer therapeutics. Increased mitochondrial fusion and mitochondrial ROS are found in arecoline treated condition as compared to control in Cal33 cells. Additionally, arecoline contributes to NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in Cal33 cells. Inhibition of mtROS by MitoTEMPO suppressed the arecoline-mediated NLRP3 inflammasome activation. BS-I induces mitochondrial fission by promoting DRP1S616 phosphorylation and activates PINK Parkin-mediated mitophagy to eliminate the dysfunctional mitochondrial population in Cal33 and FaDu cells. In parkin deficient conditions, BS-I induced mitophagy is compromised, whereas mitochondrial fission is still evident in Hela Cells. BS-I further hinders arecoline-induced mitochondrial ROS production and NLRP3 inflammasome activation in Cal33 cells. Inhibition of mitochondrial fission through Mdiv1 and mitophagy through Wortmannin and ShParkin significantly hampers the inflammasome inhibition by BS-I. These results established that BS-I-induced mitochondrial fission and mitophagy help in the segregation and subsequent removal of damaged mitochondrial sub-population, which contributes to NLRP3 inflammasome inhibition in oral cancer cells.
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Appears in Collections:Conference Papers

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