Cross-resistance and collateral sensitivity to natural product drugs in cisplatin-sensitive and -resistant rat lymphoma and human ovarian carcinoma cells

Cancer Chemotherapy and Pharmacology
H Parekh, H Simpkins

Abstract

The cytotoxicity of mitotic spindle poisons, vinca alkaloids and the anthracycline, adriamycin, against cisplatin-sensitive and -resistant rat lymphoma and human ovarian carcinoma cell lines was investigated. Interestingly, it was found that all cell lines were more sensitive to the mitotic spindle poisons, vincristine and vinblastine. Adriamycin was the least effective and taxol had intermediate activity. The Walker rat lymphoma cell line resistant to cisplatin (WR) exhibited the multiple drug resistance phenotype since it showed collateral resistance to all drugs (ranging from twofold to taxol, colcemid and colchicine and sixfold to the vinca alkaloids). Verapamil potentiated the cytotoxic activity of adriamycin and vincristine in a striking fashion with the Walker cells. P-glycoprotein was found to be present in the plasma membranes of the Walker cells with approximately a 2.5-fold increase in the WR as compared to the sensitive (WS) cells. Glutathione levels were elevated in all of the cisplatin-resistant cell lines when compared to the cisplatin-sensitive parental cell lines. A profound effect of buthionine sulfoximine pretreatment on adriamycin cytotoxicity was observed. Glutathione S-transferase (pi) was present in all t...Continue Reading

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Citations

Sep 30, 2006·Cancer Chemotherapy and Pharmacology·Bih Fang Pan, J Arly Nelson
Oct 19, 2010·Cancer Chemotherapy and Pharmacology·Jianli ChenHenry Simpkins
Aug 1, 1997·General Pharmacology·H Parekh, H Simpkins
Sep 19, 2009·Trends in Pharmacological Sciences·Matthew D HallMichael M Gottesman
Nov 14, 2006·International Journal of Radiation Oncology, Biology, Physics·Dong W KimBapsi Chakravarthy
Apr 3, 2014·Biochemical and Biophysical Research Communications·Jianli ChenHenry Simpkins
Feb 14, 2002·The Journal of Biological Chemistry·Hong Bing DengHenry Simpkins

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