Photoactivation of pheophorbide-a utilizing 670 nm LEDs elicits cancer suppressive effects in androgen-independent prostate cancer cellular models.

Abstract

Prostate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer death in men in the USA. Photodynamic therapy (PDT) is a state-of-the-art treatment that combines high selectivity with minor side effects. Pheophorbide-a (Pheo) is a natural pigment with a photosensitizer property. Our study delved into the impact of Pheo alone or Pheo-PDT combination on the androgen-independent metastatic prostate cancer (AIPC) cell lines DU-145 and C4-2. Furthermore, an in-depth examination has been conducted on the photocytotoxicity mechanism of Pheo-PDT in these specific cell lines. In vitro studies were conducted using the AIPC cell lines. DU-145 and C4-2 cells were treated with Pheo at different concentrations for 60 min alone, or Pheo treatment followed by exposure to 670 nm illumination (60 mW/cm2 in 88 s pulses), producing 5 J/cm2 via portable light-emitting diode. Our results show that Pheo-PDT substantially inhibits cell viability, anchorage-independent growth, and migration capacities and induces autophagy and apoptosis via the over-production of reactive oxygen species that mediates endoplasmic reticulum stress in AIPC cell lines. Our study highlights the potential benefits of Pheo-PDT in metastatic hormone-insensitive PCa cell lines. It paves the way for treating localized and locally advanced PCa as a possible candidate for castration-resistant prostate cancer.