DNA Repair in Despair-Vitamin D Is Not Fair.
The role of vitamin D as a treatment option for neoplastic diseases, once considered to have a bright future, remains controversial. The preclinical studies discussed herein show compelling evidence that Vitamin D Derivatives (VDDs) can convert some cancer and leukemia cells to a benign phenotype, by differentiation/maturation, cell cycle arrest, or induction of apoptosis. Furthermore, there is considerable, though still evolving, knowledge of the molecular mechanisms underlying these changes. However, the attempts to clearly document that the treatment outcomes of human neoplastic diseases can be positively influenced by VDDs have been, so far, disappointing. The clinical trials to date of VDDs, alone or combined with other agents, have not shown consistent results. It is our contention, shared by others, that there were limitations in the design or execution of these trials which have not yet been fully addressed. Based on the connection between upregulation of JNK by VDDs and DNA repair, we propose a new avenue of attack on cancer cells by increasing the toxicity of the current, only partially effective, cancer chemotherapeutic drugs by combining them with VDDs. This can impair DNA repair and thus kill the malignant cells, warranting a comprehensive study of this novel concept. J. Cell. Biochem. 117: 1733-1744, 2016. © 2016 Wiley Periodicals, Inc.
Faculty of Biotechnology, Department of Proteins Biotechnology, University of Wrocław, Joliot-Curie 14A Street, Wrocław 50-383, Poland.
Elżbieta
E
Gocek
Department of Pathology and Laboratory Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, 185 South Orange Avenue, Newark, 07103, New Jersey, USA.
George P
GP
Studzinski
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D014807:Vitamin D / Q000378:metabolism / Q000494:pharmacology
D014807:Vitamin D
APOPTOSIS; CALCITRIOL; CELL CYCLE; DIFFERENTIATION; VITAMIN D; VITAMIN D DERIVATIVES