p53-dependent antiproliferative and antitumor effect of novel alkyl series of diorganotin(IV) compounds
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Purpose: A series of diorganotin(IV) dichloride complexes of N-(2-pyridylmethylene)arylamine (nitrogen-chelating ligands) have been synthesized and characterized. The present study was carried out to investigate the comparative anti-proliferative and anti-tumor effect of Me2SnCl2.L1 (OTC-1), Et2SnCl2.L2 (OTC-2) and nBu2SnCl.L2 (OTC-3) in combination with X-rays (1.5 Gy). Method: The cytotoxicity of these diorganotin(IV) compounds was studied in human peripheral lymphocytes and the antitumor activity was assessed in Dalton’s lymphoma cells. The involvement of proteins that regulate cell cycle and apoptosis was investigated to elucidate the mechanism of their action. Results: 5 mg kg−1 of OTC-3 showed better antiproliferative and antitumor activity than OTC-1 and OTC-2, both as alone or in combination with X-rays. The maximum enhancement of exchange aberrations and the level of p53 and p16 proteins were observed in the OTC-3 treated samples. Upregulated expression of p53 caused a significant down-regulated transcriptionally repression of Survivin in OTC-3 treated human lymphocytes. Conclusion: It could be possible that after treatment with either OTC-3 alone or in combination with X-rays the Dalton’s lymphoma cells may die apoptotically after inducing initial delay in cell cycle and thereby survivality of mouse bearing Dalton’s Lymphoma cells was increased significantly.
KeywordsDiorganotin(IV) Antiproliferation Anti-tumor Apoptosis
This work was supported partly by grants from the Council of Scientific and Industrial Research, New Delhi, India (Grant No. 9/347(118)/97/EMR-I) and partly by grants from the University Potential for Excellence Programme from University Grants Commission, New Delhi to AC and from the Department of Science and Technology, New Delhi, India (Grant No. SR/SI/IC-03/2005) to TSBB.
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