Mitochondrial voltage-dependent anion channels (VDACs) as novel pharmacological targets for anti-cancer agents

被引：65

作者：

Simamura, Eriko ^{[1
]}

Shimada, Hiroki ^{[1
]}

Hatta, Toshihisa ^{[1
]}

Hirai, Kei-Ichi ^{[1
]}

机构：

[1] Kanazawa Med Univ, Dept Mol & Cell Struct Sci, Uchinada, Ishikawa 9200293, Japan

来源：

JOURNAL OF BIOENERGETICS AND BIOMEMBRANES | 2008年 / 40卷 / 03期

基金：

日本学术振兴会;

关键词：

mitochondria; voltage-dependent anion channel (VDAC); pharmacological target; anti-cancer agent; apoptosis; reactive oxygen species (ROS); adenine nucleotide translocator; hexokinase;

D O I：

10.1007/s10863-008-9158-6

中图分类号：

Q6 [生物物理学];

学科分类号：

071011 ;

摘要：

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.

引用

页码：213 / 217

页数：5

共 29 条

[1] VDAC1 is a transplasma membrane NADH-ferricyanide reductase [J].

Baker, MA ;

Lane, DJR ;

Ly, JD ;

De Pinto, V ;

Lawen, A .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (06) :4811-4819

[2]

BLACHLYDYSON E, 1993, J BIOL CHEM, V268, P1835

[3] VDAC2 inhibits BAK activation and mitochondrial apoptosis [J].

Cheng, EHY ;

Sheiko, TV ;

Fisher, JK ;

Craigen, WJ ;

Korsmeyer, SJ .

SCIENCE, 2003, 301 (5632) :513-517

[4]

Colombini M, 1980, Ann N Y Acad Sci, V341, P552, DOI 10.1111/j.1749-6632.1980.tb47198.x

[5] Apoptosis - A cellular poison cupboard [J].

Earnshaw, WC .

NATURE, 1999, 397 (6718) :387-+

[6] Furanonaphthoquinone analogs possessing preferential antitumor activity compared to normal cells [J].

Hirai, KI ;

Koyama, J ;

Pan, JH ;

Simamura, E ;

Shimada, H ;

Yamori, T ;

Sato, S ;

Tagahara, K ;

Tsuruo, T .

CANCER DETECTION AND PREVENTION, 1999, 23 (06) :539-550

[7] Human mitochondrial transmembrane metabolite carriers: Tissue distribution and its implication for mitochondrial disorders [J].

Huizing, M ;

Ruitenbeek, W ;

van den Heuvel, LP ;

Dolce, V ;

Iacobazzi, V ;

Smeitink, JAM ;

Palmieri, F ;

Trijbels, JMF .

JOURNAL OF BIOENERGETICS AND BIOMEMBRANES, 1998, 30 (03) :277-284

[8] Oblimersen bcl-2 antisense: Facilitating apoptosis in anticancer treatment [J].

Klasa, RJ ;

Gillum, AM ;

Klem, RE ;

Frankel, SR .

ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT, 2002, 12 (03) :193-213

[9]

Lai JC, 2005, MOL CANCER THER, V4, P305

[10] A pharmacologic target of G3139 in melanoma cells may be the mitochondrial VDAC [J].

Lai, Johnathan C. ;

Tan, Wenzhi ;

Benimetskaya, Luba ;

Miller, Paul ;

Colombini, Marco ;

Stein, C. A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (19) :7494-7499

← 1 2 3 →