Effect of meta-tetra(hydroxyphenyl)chlorin (mTHPC)-mediated photodynamic therapy on sensitive and multidrug-resistant human breast cancer cells

Meta-tetra(hydroxyphenyl)chlorin (mTHPC) is in clinical trials for the phot odynamic therapy (PDT) of localized-stage cancer. The PDT susceptibility of cells expressing multidrug resistance (MDR) phenotype is an attractive pos sibility to overcome the resistance to cytotoxic drugs observed during canc er chemotherapy. The accumulation, photocytotoxicity and intracellular loca lization of mTHPC were examined using the doxorubicin selected MCF-7/DXR hu man breast cancer cells, expressing P-glycoprotein (P-gp), and the wild-typ e parental cell line, MCF-7. No significant difference in mTHPC accumulatio n was observed between the two cell lines up to 3 h contact. The photodynam ic activity of mTHPC, measured 24 h after irradiation with red laser light (lambda =650 nm), was significantly greater in MCF-7/DXR as compared to MCF -7 cells. A light dose of 2.5 J cm(-2) inducing 50% of cytotoxicity in MCF- 7, resulted in 85% cytotoxicity in MCF-7/DXR. The presence of P-gp inhibito rs SDZ-PSC-833 and cyclosporin A did not modify the mTHPC-induced cytotoxic ity. The difference in intracellular mTHPC distribution pattern between two cell lines may contribute to different photocytotoxicity. Our results indi cate that mTHPC mediated PDT could be useful in killing cells expressing NM R phenotype. (C) 2001 Elsevier Science B.V. All rights reserved.