p53-dependent antiproliferative and antitumor effect of novel alkyl series of diorganotin(IV) compounds.

Abstract

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 Me(2)SnCl(2.)L(1) (OTC-1), Et(2)SnCl(2.)L(2) (OTC-2) and (n)Bu(2)SnCl. L(2) (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.

• Authors: Biplob Koch, Tushar S Basu Baul, Anupam Chatterjee
• Journal: Investigational new drugs (Invest New Drugs) Vol. 27 Issue 4 Pg. 319-26 (Aug 2009) ISSN: 1573-0646 [Electronic] United States
• PMID: 18802665 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Organotin Compounds
• Tumor Suppressor Protein p53

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Drug Screening Assays, Antitumor
• Gene Expression Regulation (drug effects)
• Humans
• Lymphocytes (drug effects, metabolism)
• Lymphoma (drug therapy)
• Male
• Mice
• Organotin Compounds (chemistry, pharmacology)
• Tumor Suppressor Protein p53 (drug effects, metabolism)
• X-Rays