Role of biological clocks in cancer processes and chronotherapy

Abstract

Biological rhythms are considered in the rational use of therapeutic agents to optimize the treatment of several diseases. In cancer, several stages of cell cycle are regulated by the circadian clock. Clock genes play a vital role in cell proliferation and apoptosis. Therefore, mutation/abnormal function of circadian clock genes could result in tumor development. Circadian rhythmicity can be used as a marker rhythm for tumor progression, as rhythm impairment increases along with tumor malignancy. Administration of drugs at a particular circadian phase has achieved the best anti-tumor activity. Pharmacological doses of melatonin significantly increase antioxidant levels, thereby decreasing free radical formation. In some cancer cell types, melatonin is known to inhibit cancer cell growth under in vitro conditions. The protective effect of S-allylcysteine, diallyl disulphide and α-ketoglutarate on NDEA treated rats showed that alternations in the rhythmicities of lipid peroxidation (TBARS) and antioxidant levels (SOD, CAT, GSH and GP_X) could be normalized.

Keywords:

• circadian clock
• cancer
• chronotherapy
• melatonin
• antioxidant