Mitochondrial voltage-dependent anion channels (VDACs) as novel pharmacological targets for anti-cancer agents |
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| Authors: | Eriko Simamura Hiroki Shimada Toshihisa Hatta Kei-Ichi Hirai |
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| Institution: | (1) Department of Molecular and Cell Structural Science, Kanazawa Medical University, Ishikawa Uchinada, 920-0293, Japan |
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| Abstract: | Recently, it was demonstrated that some anti-cancer agents used mitochondrial voltage-dependent anion channels (VDAC1–3 isoforms)
as their pharmacological target. VDACs are expressed more highly in cancer cells than normal cells; thus the VDAC-dependent
cytotoxic agents can have cancer-selectivity. Furanonaphthoquinones (FNQs) induced caspase-dependent apoptosis via the production
of NADH-dependent reactive oxygen species (ROS) by VDAC1. The ROS production and the anti-cancer activity of FNQs were increased
by VDAC1 overexpression. Meanwhile, erastin induced RAS-RAF-MEK-dependent non-apoptotic cell death via VDAC2. On the other
hand, VDACs were needed for transporting ATP to hexokinase (HK), which was highly expressed in cancer cells. We hypothesized
that the high glycolysis might induce up-regulation of VDAC. In this review, we propose that VDACs are novel candidates for
effective pharmacological targets of anti-cancer drugs. |
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| Keywords: | Mitochondria Voltage-dependent anion channel (VDAC) Pharmacological target Anti-cancer agent Apoptosis Reactive oxygen species (ROS) Adenine nucleotide translocator Hexokinase |
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