Speaker
Description
Photodynamic therapy (PDT) has emerged as a promising alternative or adjunct modality for the treatment of breast cancer. PDT relies on the activation of a photosensitizer (PS) by red or near-infrared light, resulting in the generation of reactive oxygen species (ROS) that induce localized tumor cell damage. Naturally derived tetrapyrrolic PSs have attracted considerable interest due to their favor-able photophysical characteristics. Pheophorbide-a, a chlorophyll-derived tetrapyrrole, demonstrates strong absorption in the red region, efficient singlet oxygen generation, preferential tumor accumula-tion, and minimal dark toxicity. Although Doxorubicin remains one of the most widely used chemo-therapeutic agents for breast cancer treatment, its prolonged administration is associated with the de-velopment of multidrug resistance, largely mediated by P-glycoprotein overexpression. PDT has shown potential efficacy in overcoming chemoresistant phenotypes. In this study, we comparatively evaluat-ed the in vitro phototherapeutic efficacy of pheophorbide-a against wild-type MCF-7 breast cancer cells and Doxorubicin-resistant MCF-7 (MCF-7/DOX) cells using 660 nm light irradiation.
Both cell subtypes were incubated with varying concentrations of pheophorbide-a for 3 h under dark conditions, followed by irradiation with a 660 ± 20 nm LED source at a fluence of 1 J/cm² and a power density of 7.08 mW/cm². Cell viability was assessed 24 h post-irradiation using the MTT assay. The results demonstrated differential sensitivity between the two cell lines. Approximately 90% reduc-tion in cell viability was observed in wild-type MCF-7 cells at 1.6 µM pheophorbide-a, whereas a high-er concentration of 2.4 µM was required to induce a comparable level of cytotoxicity in MCF-7/DOX cells, indicating moderate resistance in the chemoresistant phenotype. Morphological observations further supported these findings. Wild-type MCF-7 cells exhibited significant cellular shrinkage, membrane disruption, and extensive cell death following the PDT. In contrast, MCF-7/DOX cells showed comparatively moderate cytotoxic effects, with approximately 30–40% of cells retaining viable morphology at the same treatment dose.
Overall, pheophorbide-a–mediated PDT demonstrated substantial phototoxic activity against both wild-type and Doxorubicin-resistant breast cancer cells, although higher concentrations were necessary to achieve similar efficacy in resistant cells. These findings suggest that plant-derived chlorophyll-based tetrapyrrolic photosensitizers hold promise as effective PDT agents for targeting multidrug-resistant breast carcinomas. Further mechanistic investigations are required to elucidate the underlying cell death signaling pathways and molecular mechanisms at protein, gene, and transcriptomic levels to enhance translational applicability.
