Drugs targeting mitochondrial functions to control tumor cell growth.
Mitochondria, the power houses of the cell, are at the cross-road of many cellular pathways. They play a central role in energy metabolism, regulate calcium flux and are implicated in apoptosis. Mitochondrial dysfunctions have been associated with various physiopathological disorders, especially neurodegenerative diseases and cancer. Structurally diverse pharmacological agents have shown direct effects on mitochondria ultra-structures and functions, either at the DNA level or upon targeting proteins located in the inner or outer mitochondrial membranes. The brief review deals with the molecular targets and mechanisms of action of chemically diverse small molecules acting on specific mitochondrial loci, such as the respiratory chain, DNA biogenesis, potassium channels, the Bcl-2 protein and the permeability transition pores (PTP). Drugs, which specifically compromise the structural and functional integrity of mitochondria, may provide novel opportunities to combat cancer cell proliferation, providing that these molecules can be selectively delivered to tumor sites. Different examples reported here show that mitochondrial insult or failure can rapidly lead to inhibition of cell survival and proliferation. Mitochondrial impairment may be a successful anti-cancer strategy.
Dias
Nathalie
N
INSERM U-524 et Laboratoire de Pharmacologie Antitumorale du Centre Oscar Lambret, IRCL, 59045 Lille, France.
Bailly
Christian
C
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000096:biosynthesis; D004579:Electron Transport / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects
D000970:Antineoplastic Agents; D004272:DNA, Mitochondrial; D015221:Potassium Channels