Photodynamic therapy using pheophorbide and 670Â nm LEDs exhibits anti-cancer effects in-vitro in androgen dependent prostate cancer

Prostate cancer (PCa) is the third leading cause of death in men in the United States and its treatment options include surgery, anti-hormonal drugs for androgen sensitive tumors, and radiotherapy. An alternative treatment is the use of photodynamic therapy (PDT), which involves the activation of a photosensitizer by a defined wavelength of light in the presence of oxygen, generating transient concentrations of reactive oxygen species (ROS). In this study, we explored the anti-cancer potential and mechanism of action of PDT using pheophorbide (Pheo) as a photosensitizer in combination with 670 nm LEDs. Our hypothesis was that Pheo-PDT combination will demonstrate anti-cancer activity against androgen dependent PCa (ADPC), suggesting an alternative and less toxic cancer treatment. Pheo-PDT demonstrated significant anti-cancer activity against ADPC in as little as 5 J/cm2 with increased effects, in a Pheo concentration dependent manner. We also observed in vitro inhibition in the clonogenic potential, as well as significant inhibition of invasion and migration, implicating the anti-metastatic activity of Pheo-PDT on PCa. Furthermore, Pheo-PDT caused G0/G1 cell cycle arrest. The oncolytic activity of PDT involves the generation of ROS, and we demonstrated immediate ROS formation subsequent to Pheo-PDT as well. Mechanistic analysis suggested that the anti-cancer activity of Pheo-PDT is via ER stress, along with inhibition of important cell growth and proliferation markers. Hence, we conclude that Pheo-PDT proves to be a potential therapeutic strategy against ADPC.