Open AccessAspirin induces cell death by directly modulating mitochondrial voltage-dependent anion channel (VDAC)
Author(s) -
Debanjan Tewari,
Dhriti Majumdar,
Sirisha Vallabhaneni,
Amal Kanti Bera
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep45184
Subject(s) - voltage dependent anion channel , aspirin , microbiology and biotechnology , chemistry , mitochondrion , programmed cell death , apoptosis , biophysics , biochemistry , biology , bacterial outer membrane , gene , escherichia coli
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 m ), upon aspirin treatment. Aspirin augmented ATP and ionomycin-induced mitochondrial Ca 2+ 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.