Abstract 1672: Photodynamic therapy using photosensitizer and light emitting diodes (LEDs) demonstrates oncolytic activity against prostate cancer

Abstract

Abstract Prostate cancer (PCa) affects over 2 million Americans and its treatment options include surgery, anti-hormonal drugs for androgen sensitive tumors, and radiotherapy. However, patients undergoing androgen deprivation therapy develop resistance leading to development of castration resistant or androgen independent PCa. It is clear there is an urgent need to find an effective treatment strategy to manage aggressive PCa. 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. We hypothesize that PDT via a photosensitizer (pheophorbide) in combination with light emitting diodes (LEDs) [670 nm] will demonstrate oncolytic activity against PCa cells, thus suggesting an alternative, less toxic cancer treatment. To test our hypothesis, we used C4-2 and DU-145 PCa cell lines as an in vitro model in this study. To explore the anti-cancer effects of PDT on PCa, cell viability assay and wound healing assay were performed. Western blotting was employed to identify the signaling molecules modulated by PDT. Our cell viability assay results demonstrated significant oncolytic activity against PCa cell lines using PDT with pheophorbide as a photosensitizer combined with 670 nm LEDs in as little as an 88 second pulse with increased lytic activity correlating with elevated energy intensities. We also observed variability in cell line PDT susceptibility; wherein, C4-2 cells were more susceptible than DU-145 PCa cells. The wound healing assay results with pheophorbide and 670 nm LEDs demonstrated significant inhibition of migration abilities of both C4-2 and DU-145 PCa cells. These findings implicate the anti-metastatic activity of PDT on PCa. Further, our mechanistic analysis showed activation of BiP/GRP78, an endoplasmic reticulum (ER) chaperone, in C4-2 as well as DU-145 PCa cells. This suggests that the anti-cancer activity of PDT with pheophorbide and 670 nm LEDs is via ER stress. In conclusion, our results show PDT using pheophorbide and 670 nm LEDs as a promising therapeutic strategy for PCa. Citation Format: Taher Gheewala, Troy Skwor, Gnanasekar Munirathinam. Photodynamic therapy using photosensitizer and light emitting diodes (LEDs) demonstrates oncolytic activity against prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1672.