Aspirin induces cell death by directly modulating mitochondrial voltage-dependent anion channel (VDAC).
Aspirin induces apoptotic cell death in various cancer cell lines. Here we showed that silencing of VDAC1 protected HeLa cells from aspirin-induced cell death. Compared to the wild type cells, VDAC1 knocked down cells showed lesser change of mitochondrial membrane potential (Δψm), upon aspirin treatment. Aspirin augmented ATP and ionomycin-induced mitochondrial Ca2+uptake which was abolished in VDAC1 knocked down cells. Aspirin dissociated bound hexokinase II (HK-II) from mitochondria. Further, aspirin promoted the closure of recombinant human VDAC1, reconstituted in planar lipid bilayer. Taken together, these results imply that VDAC1 serves as a novel target for aspirin. Modulation of VDAC1 is possibly associated with the cell death and anticancer effects of aspirin.
Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences Building, Indian Institute of Technology Madras, Chennai 600036, India.
Debanjan
D
Tewari
Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences Building, Indian Institute of Technology Madras, Chennai 600036, India.
Dhriti
D
Majumdar
Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences Building, Indian Institute of Technology Madras, Chennai 600036, India.
Sirisha
S
Vallabhaneni
Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences Building, Indian Institute of Technology Madras, Chennai 600036, India.
Amal Kanti
AK
Bera
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001241:Aspirin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D006367:HeLa Cells; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D050995:Voltage-Dependent Anion Channel 1 / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000255:Adenosine Triphosphate; D050995:Voltage-Dependent Anion Channel 1; D006593:Hexokinase; D001241:Aspirin; D002118:Calcium