Trans-dichlorooxovandium (IV) complex as a novel photoinducible DNA interstrand crosslinker for cancer therapy

Somyajit, Kumar and Banik, Bhabatosh and Saxena, Sneha and Babu, Sharath and Hande, Manoor Prakash and Chakravarty, Akhil R and Nagaraju, Ganesh (2016) Trans-dichlorooxovandium (IV) complex as a novel photoinducible DNA interstrand crosslinker for cancer therapy. In: CARCINOGENESIS, 37 (2). pp. 145-156.

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Abstract

Although DNA interstrand crosslinking (ICL) agents such as mitomycin C, cisplatin and psoralen serve as potent anticancer drugs, these agents are known to have dose-limiting toxic effects on normal cells. Moreover, tumor resistance to these agents has been reported. Here, we show that trans-dichlorooxovanadium (IV) complex of pyrenyl terpyridine (VDC) is a novel photoinducible DNA crosslinking agent. By a combination of in vitro and ex vivo experiments including plasmid-based assays, we find that VDC forms monoadducts on the DNA and can be activated by UV-A and visible light to generate DNA interstrand crosslinks. VDC efficiently activates Fanconi anemia (FA) pathway of DNA interstrand crosslink repair. Strikingly, photoinduction of VDC induces prolonged activation of cell cycle checkpoint and a high degree of cell death in homologous recombination (HR)/ICL repair defective cells. Moreover, VDC specifically targets cells that express pathological RAD51C mutants. These data imply that VDC can be potentially used for cancer therapy and suggest that tumors arising in patients with gene mutations in FA and HR repair pathway can be specifically targeted by a photoactivatable VDC.

Item Type:	Journal Article
Publication:	CARCINOGENESIS
Publisher:	OXFORD UNIV PRESS
Additional Information:	Copy right for this article belongs to the OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
Department/Centre:	Division of Biological Sciences > Biochemistry Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	06 Apr 2016 07:13
Last Modified:	06 Apr 2016 07:13
URI:	http://eprints.iisc.ac.in/id/eprint/53630

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