Promotion of PDT efficacy by HA14-1

David Kessel; Michael Price; Kelly Haagenson

doi:10.1117/12.758836

8 February 2008 Promotion of PDT efficacy by HA14-1

David Kessel, Michael Price, Kelly Haagenson

Proceedings Volume 6845, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XVII; 684502 (2008) https://doi.org/10.1117/12.758836
Event: SPIE BiOS, 2008, San Jose, California, United States

Abstract

Photodynamic therapy (PDT) can target the members of the Bcl-2 family that protect cells from the initiation of apoptosis, a well-known death pathway. We examined the ability of HA14-1, a non-peptidic Bcl-2/Bcl-xL antagonist, to promote the efficacy of PDT. The photosensitizer was the porphycene CPO that causes photodamage to Bcl-2 located in the endoplasmic reticulum. Using low PDT doses together with LD5-20 concentrations of HA14-1, we found a marked synergistic effect. These results indicate that such an effect occurs when PDT is coupled with pharmacologic suppression of Bcl-2 function. HA14-1 is an unstable compound that decomposes in aqueous solution. This resulted in a rapid (~60 sec) burst of fluorescence that closely mimicked the properties of many fluorescent probes, but was traced to an effect produced when HA14-1 contacts serum proteins. Other Bcl-2 antagonists that do not produce any intrinsic fluorescence also promoted PDT efficacy. Moreover, briefly storing HA14-1 in aqueous medium until the fluorescent burst is over does not inhibit a subsequent synergistic promotion of PDT efficacy. We conclude that Bcl-2 antagonists can promote the efficacy of low-dose PDT in a manner unrelated to ROS production. The most likely explanation is an enhanced loss of anti-apoptotic Bcl-2 family function such that a threshold for initiation of apoptosis is crossed.

Citation Download Citation

David Kessel, Michael Price, and Kelly Haagenson "Promotion of PDT efficacy by HA14-1", Proc. SPIE 6845, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XVII, 684502 (8 February 2008); https://doi.org/10.1117/12.758836

ACCESS THE FULL ARTICLE

INSTITUTIONAL
Select your institution to access the SPIE Digital Library.

SELECT YOUR INSTITUTION

PERSONAL
Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.

PERSONAL SIGN IN

No SPIE Account? Create one

PURCHASE THIS CONTENT

SUBSCRIBE TO DIGITAL LIBRARY

50 downloads per 1-year subscription

Members: $195

Non-members: $335 ADD TO CART

25 downloads per 1 - year subscription

Members: $145

Non-members: $250 ADD TO CART

PURCHASE SINGLE ARTICLE

Includes PDF, HTML & Video, when available