Mitochondrial contributions to cancer cell physiology: redox balance, cell cycle, and drug resistance.
Alterations in the biochemistry of mitochondria have been associated with cell transformation and the acquisition of drug resistance to certain chemotherapeutic agents, suggesting that mitochondria may play a supportive role for the cancer cell phenotype. Mitochondria are multifunctional organelles that contribute to the cellular adenosine triphosphate (ATP) pool and cellular redox balance through the production of reactive oxygen intermediates (ROI). Our laboratory has focused on these mitochondrial functions in the context of cancer cell physiology to evaluate the potential role of mitochondria as controllers of tumour cell proliferation. Low concentrations of ROI have been implicated as messengers in intracellular signal transduction mechanisms; thus an imbalance of ROI production from the mitochondria may support cancer cell growth. In addition, suppression of mitochondrial ATP production can halt cell cycle progression at two energetic checkpoints, suggesting that the use of tumor-selective agents to reduce ATP production may offer a therapeutic target for cancer growth control.
Dorward
A
A
Hamilton Regional Cancer Centre, Hamilton, Ontario, Canada.
Sweet
S
S
Moorehead
R
R
Singh
G
G
D000970:Antineoplastic Agents / Q000494:pharmacology; D002453:Cell Cycle; D019008:Drug Resistance, Neoplasm; D004734:Energy Metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D010084:Oxidation-Reduction; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents