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 cis platin. 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 twofold increase in doxorubicin toxicity in both cell lines. MB and TBO, however, increased doxorubicin toxicity in EMT6-R cells x 2 and x 3 respectively, but had less effect on the sensitive cell line (increase x 1.4 and x 2 respectively). Thus MB and TBO may act on the MDR cell line via a different mechanism to that of VBBO.