Comparative study of tetrapyrrolic photosensitizer mediated phototherapy against breast cancer cell subtypes

The effectiveness of anticancer therapies like chemotherapy and radiotherapy is primarily limited by the development of multidrug-resistant cancer cells, leading to enhanced progression, invasiveness, and tumor metastasis with poor clinical outcomes. Clinical findings suggest that employing mechanistically distinct therapies can overcome the resistance. Photodynamic Therapy (PDT), a photochemical-based anticancer treatment modality is a promising strategy to kill chemotherapeutic drug-resistant cancer cells. Several plant-based PSs have been used due to their phototoxic efficacy and minimum adverse side effects. In this study, Pheophorbide-a (PPa), a chlorophyll derivative is being used as a potential photosensitizer to induce cell death in P-glycoprotein over-expressing Doxorubicin (DOX) resistant MCF-7 breast cancer cells. Wild-type MCF-7 and MCF-7/DOX cancer cells were treated with a different concentration of PPa followed by irradiation with a 660 nm red laser at a light dose of 1 J/cm². The PPa-induced phototoxicity was evaluated by 3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) proliferation assay and by analyzing cellular morphological changes, cell death assay. Results showed that PPa induced significant photodynamic cell death in Doxorubicin-resistant cancer cells in a dose-dependent manner. Morphological analysis and fluorescent staining techniques showed the features of cell death following PDT, including cellular shrinkage, cytoplasmic condensation, and nuclear and cell membrane damage. Our results indicate that PDT mediated by chlorophyll-based tetrapyrrole PSs like PPa could be effective for the eradication of chemo-drug resistant cancers.