Please use this identifier to cite or link to this item: http://hdl.handle.net/2080/3928
Title: SIRT1 Downregulation Directs Mitochondrial Hyperfusion for Inhibition of Apoptosis in Cisplatin-Treated Oral Cancer Cells
Authors: Patra, Srimanta
Bhutia, Sujit Kumar
Keywords: Apoptosis
Gallic acid
Mito-bulbs
Mitochondrial hyperfusion
Oral cancer
SIRT1
Issue Date: Dec-2022
Citation: International Conference on Recent Advances in Biological Sciences -2022 (RABS-2022), Vikram Deb Autonomous College, Jeypore, Odisha, India, 23-24 December 2022
Abstract: SIRT1 (NAD-dependent protein deacetylase sirtuin-1), a class III HDAC acting as a tumor suppressor gene, is downregulated in oral cancer cells. Optimal doses of cisplatin (CDDP) are found to downregulate SIRT1 expression advocating the mechanism of drug resistance. SIRT1 downregulation orchestrates inhibition of DNM1L-mediated mitochondrial fission, subsequently leading to the formation of hyperfused mitochondrial networks. The hyperfused mitochondrial networks preserve the release of cytochrome C by stabilizing the mitochondrial inner membrane cristae (formation of mitochondrial nucleoids clustering mimicking mito-bulb like structures) to inhibit apoptosis. Overexpression of SIRT1 reverses the mitochondrial hyperfusion by initiating DNM1L-FIS1-regulated mitochondrial fission. In the overexpression conditions, inhibition of mitochondrial hyperfusion and nucleoid clustering (mito-bulbs) facilitates the cytoplasmic release of cytochrome C to induce apoptosis in oral cancer cells. Further, low-dose priming with gallic acid (GA), a bio-active SIRT1 activator, also nullifies CDDP-mediated inhibition of apoptosis by reducing mito-bulb formation. When SIRT1 is knocked down from the GA-primed cells, the activation of apoptosis is found to be reversed. Similarly, SIRT1 overexpression in the CDDP resistance oral cancer polyploid giant cancer cells (PGCCs) re-sensitizes the cells to apoptosis. Further, synergistically treated with CDDP, gallic acid induces apoptosis in the oral cancer PGCCs by inhibiting mitochondrial hyperfusion.
Description: Copyright belongs to proceeding publisher
URI: http://hdl.handle.net/2080/3928
Appears in Collections:Conference Papers

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