Cytotoxicity and adjuvant activity of cationic photosensitizers in a multidrug resistant cell line.

The toxicities and phototoxicities of methylene blue (MB), toluidine blue O (TBO) and Victoria blue BO (VBBO) in a murine mammary tumour cell line (EMT6-S) and a multidrug resistant (MDR) sub-line (EMT6-R) were measured and their efficacy against the resistant sub-line was compared to that of doxorubicin and cis-platinum. The MDR cell line was considerably more susceptible to VBBO than to the conventional agent doxorubicin. VBBO was also phototoxic whereas illumination did not alter the activity of doxorubicin or of cisplatin. Both TBO and MB showed limited light activation (2-fold) in both the sensitive and resistant cell lines. Pre-treatment with VBBO prior to exposure to doxorubicin caused a two-fold increase in doxorubicin toxicity in both cell lines. MB and TBO, however, increased doxorubicin toxicity in EMT6-R cells x2 and x3 respectively, but had less effect on the sensitive cell line (increase x1.4 and x2 respectively). Thus MB and TBO may act on the MDR cell line via a different mechanism to that of VBBO.