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Aspirin induces cell death by directly modulating mitochondrial voltage-dependent anion channel (VDAC).

ABSTRACT: 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 (??m), 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.

SUBMITTER: Tewari D

PROVIDER: S-EPMC5361111 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Aspirin induces cell death by directly modulating mitochondrial voltage-dependent anion channel (VDAC).

Tewari Debanjan D Majumdar Dhriti D Vallabhaneni Sirisha S Bera Amal Kanti AK

Scientific reports 20170322

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 (Δψ<sub>m</sub>), upon aspirin treatment. Aspirin augmented ATP and ionomycin-induced mitochondrial Ca<sup>2+</sup> uptake which was abolished in VDAC1 knocked down cells. Aspirin dissociated bound hexokinase II (HK-II) from ...[more]

PMID: 28327594

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