Targeted photodynamic therapy for prostate cancer: Inducing apoptosis via activation of the caspase-8/-3 cascade pathway

  • Authors:
    • Tiancheng Liu
    • Lisa Y. Wu
    • Joseph K. Choi
    • Clifford E. Berkman
  • View Affiliations

  • Published online on: April 1, 2010     https://doi.org/10.3892/ijo_00000553
  • Pages: 777-784
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Abstract

The limitation of specific delivery of photosensitizers to tumor sites, represents a significant shortcoming of photodynamic therapy (PDT) application at present. Prostate-specific membrane antigen (PSMA), a validated biomarker for prostate cancer, has attracted considerable attention as a target for imaging and therapeutic applications for prostate cancer. The present study focuses on the investigation of a PSMA inhibitor-conjugate of pyropheophorbide-a (Ppa-conjugate 2.1) for a targeted PDT application and the mechanism of its mediated-cell death in prostate cancer cells. Multiple fluorescence labeling methods were employed to monitor PDT-treated prostate cancer cells by confocal laser scanning microscopy. Our results demonstrate that Ppa-conjugate 2.1 mediated apoptosis is specific to PSMA+ (positive) LNCaP cells, but not PSMA− (negative) PC-3 cells. Furthermore, these results indicate that following PDT, the activation of caspase-8, -3, -9, cleavage of poly(ADP-ribose) polymerase (PARP) and DNA fragmentation is sequential. The appearance of cleaved β-actin further supported involvement of caspase-3. Specific caspase inhibitor blocking studies reveal that the caspase-8/-3 cascade pathway plays a key role in apoptosis of LNCaP cells induced by Ppa-conjugate 2.1. The demonstrated selective targeting and efficacy of this agent suggests that targeted PDT could serve as an alternative treatment option for prostate cancer.

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April 2010
Volume 36 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Liu T, Wu LY, Choi JK and Berkman CE: Targeted photodynamic therapy for prostate cancer: Inducing apoptosis via activation of the caspase-8/-3 cascade pathway. Int J Oncol 36: 777-784, 2010.
APA
Liu, T., Wu, L.Y., Choi, J.K., & Berkman, C.E. (2010). Targeted photodynamic therapy for prostate cancer: Inducing apoptosis via activation of the caspase-8/-3 cascade pathway. International Journal of Oncology, 36, 777-784. https://doi.org/10.3892/ijo_00000553
MLA
Liu, T., Wu, L. Y., Choi, J. K., Berkman, C. E."Targeted photodynamic therapy for prostate cancer: Inducing apoptosis via activation of the caspase-8/-3 cascade pathway". International Journal of Oncology 36.4 (2010): 777-784.
Chicago
Liu, T., Wu, L. Y., Choi, J. K., Berkman, C. E."Targeted photodynamic therapy for prostate cancer: Inducing apoptosis via activation of the caspase-8/-3 cascade pathway". International Journal of Oncology 36, no. 4 (2010): 777-784. https://doi.org/10.3892/ijo_00000553