Antiproliferative role of vitamin D and its analogs--a brief overview.
The active metabolite of vitamin D, 1alpha, 25-dihydroxyvitamin D3 [1,25(OH)2D3]--a seco-steroid hormone is a pivotal regulator of cellular proliferation and differentiation those are independent of its classical function of calcium homeostasis and bone mineralization. The existence of the nuclear vitamin D receptor (VDR) has been found in numerous tissues in different organs, which are the so-called 'non-classical' targets of this seco-steroid hormone. Vitamin D has been documented as a potent antiproliferative agent in different tissues and cells. Epidemiological studies reveal a negative correlation between physiological level of vitamin and cancer risk. Studies using animal models clearly demonstrate protective role of vitamin D in different cancer types by the reduction in tumor progression and by monitoring biochemical parameters. Experiments with cultured human and animal cancer cell lines show similar antiproliferative role of vitamin D manifested by up or down regulations of crucial genes leading to inhibition of cellular growth. Hypercalcemia hinders broad-spectrum therapeutic uses of vitamin D in cancer chemotherapy. Application of vitamin D analogs having similar chemical structures or other compounds having vitamin D like actions but lacking calcemic adverse effects are getting significant attention towards rational therapeutics to treat cancer. The current review focuses on the application of vitamin D and its analogs in different forms of cancer and on the molecular mechanism involved in vitamin D mediated inhibition in cellular proliferation, cell cycle, induction of apoptosis and tumor suppression, which may eventually evolve as a meaningful cancer therapy.
Banerjee
Pratik
P
Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, Calcutta, India.
Chatterjee
Malay
M
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002117:Calcitriol / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018167:Receptors, Calcitriol; D002117:Calcitriol