PT  - JOURNAL ARTICLE
AU  - MARTA CARAMÉS
AU  - ANA ALONSO-VARONA
AU  - IGNACIO GARCÍA-ALONSO
AU  - TEODORO PALOMARES
TI  - Glutathione Modulators Reverse the Pro-tumour Effect of Growth Factors Enhancing WiDr Cell Response to Chemotherapeutic Agents
DP  - 2010 Apr 01
TA  - Anticancer Research
PG  - 1223--1231
VI  - 30
IP  - 4
4099  - http://ar.iiarjournals.org/content/30/4/1223.short
4100  - http://ar.iiarjournals.org/content/30/4/1223.full
SO  - Anticancer Res2010 Apr 01; 30
AB  - Background: Glutathione has been implicated in growth factor-mediated chemoresistance of colon cancer cells. Materials and Methods: We evaluated the influence of hepatocyte growth factor, vascular endothelial growth factor and epidermal growth factor on the effect of 5-fluorouracil, oxaliplatin and SN-38 (the active metabolite of irinotecan) on WiDr cells. We also analysed the effect of glutathione modulators (L-buthionine-SR-sulfoximine, and L-2-oxothiazolidine-4-carboxylate) on the growth-promoting effect induced by growth factors and on the antiproliferative activity of the aforementioned drugs. Results: Exposure to growth factors reduced drug cytotoxic activity, specially in the case of 5-fluorouracil. The addition of L-buthionine-SR-sulfoximine or L-2-oxothiazolidine-4-carboxylate to the chemotherapeutic agents abrogated pro-tumour effects of the growth factors, and produced a greater antitumour activity than the drugs alone. Conclusion: Among the combinations analysed, the addition of L-2-oxothiazolidine-4-carboxylate to SN-38 was found to be the best chemotherapeutic combination, resulting in a near 70% increase in the cytotoxic activity of SN-38. Copyright© 2010 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved