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Dipyridamole increases VP16 growth inhibition, accumulation and retention in parental and multidrug-resistant CHO cells

Lookup NU author(s): Professor Nicola Curtin

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Abstract

Dipyridamole (DP) has been shown to reverse multidrug resistance (MDR) via interactions with P-glycoprotein (P-gp). The effect of DP on VP16 growth inhibition was investigated in parental (CHO-K1) and MDR (CHO-Adr(r)) Chinese hamster ovary cells. CHO-Adr(r) cells were 18-fold resistant to VP16 and intracellular accumulation was 28% less than in CHO-K1 cells. DP reduced the resistance of CRO-Adr(r) to VP16 by a factor of 2 - 3 and caused a similar potentiation of VP16 growth inhibition in the parental cells. A time-dependent increase in intracellular VP16 accumulation, which was similar in both cell lines, was caused by DP. The intracellular retention of VP16 was increased 2- to 3-fold by DP in both cell lines. The magnitude of the effect of DP on all three parameters measured was similar (2- to 4-fold), suggesting that the increased growth inhibition was related to increased intracellular exposure to VP16 owing to the inhibition of the efflux of VP16 by DP. However, since the effect of DP was similar in both parental and P-gp-overexpressing cells it is unlikely that the potentiation of VP16 by DP is mediated via an interaction with P-gp.


Publication metadata

Author(s): Turner, R., Curtin, N.J.

Publication type: Article

Publication status: Published

Journal: British Journal of Cancer

Year: 1996

Volume: 73

Issue: 7

Pages: 856-860

Print publication date: 01/01/1996

ISSN (print): 0007-0920

ISSN (electronic): 1532-1827

PubMed id: 8611395


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