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http://hdl.handle.net/2080/4247
Title: | Bacopaside-I, An Active Component from Bacopa Monnieri, Induces PPA-Mediated Mitochondrial Fission and Mitophagy for Targeting NLRP3 Inflammasome Activation in Oral Cancer |
Authors: | Mishra, Soumya Ranjan Bhutia, Sujit Kumar |
Keywords: | Arecoline Bacopaside-I Mitophagy NLRP3 inflammasome Oral cancer |
Issue Date: | Dec-2023 |
Citation: | 46TH Annual Conference &National Seminar on "Medicinal and Aromatic Plants: Traditional knowledge and Current Research" Dhenkanal, Odisha, India, 17th-18th December 2023 |
Abstract: | Consumption of areca nut containing principal alkaloid arecoline is a major contributor to oral cancer in India. 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 inflammatory effect of arecoline for oral cancer therapeutics. Increased mitochondrial fusion and ROS are found in arecoline-treated conditions compared to control in Cal33 cells. Additionally, arecoline contributes to the NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in Cal33 cells. Inhibition of mtROS by Mito-Tempo suppressed the arecoline-mediated NLRP3 inflammasome activation. BS-I induces mitochondrial fission through the PPA2-DRP1 axis and activates PINK1-PARKIN mediated mitophagy to eliminate the dysfunctional mitochondrial population in Cal33 and FaDu cells. BS-I-induced mitophagy is compromised in parkin-deficient conditions, 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 Mdivi1 and mitophagy through CQ and siPARKIN significantly hampers the inflammasome inhibition by BS-I. These results established that BS-I-induced mitochondrial fission and mitophagy help segregate and remove damaged mitochondrial sub-population, contributing to NLRP3 inflammasome inhibition in oral cancer cells. |
Description: | Copyright belongs to proceeding publisher |
URI: | http://hdl.handle.net/2080/4247 |
Appears in Collections: | Conference Papers |
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2023_SKBhutia_Bacopaside-I.pdf | 4.04 MB | Adobe PDF | View/Open Request a copy |
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