Photodynamic Therapy Destroys Prostate Cancer Cells in Culture

Cancer researchers seeking to perfect methods of therapy that better target cancer cells with less collateral damage to normal tissues have studied the effects of PSMA (prostate-specific membrane antigen)-targeted photodynamic therapy (PDT) on the cytoskeletal networks of prostate cancer cells growing in tissue culture.

PSMA is a highly prostate-restricted membrane glycoprotein that is expressed in normal prostatic epithelial cells and elevated in prostate cancers, especially in poorly differentiated, metastatic, and hormone refractory carcinomas. It has been measured in serum with immunocompetitive and Western blot assays, and its levels have been found to be correlated with the prediction of treatment failure and disease prognosis.

Investigators at Washington State University (Pullman, USA) are among those trying to exploit PSMA for directed delivery of chemotherapeutic agents to prostate tumors. In the May 10, 2010, online edition of the journal Cancer Letters they described the use of a chemical compound, LW50, that selectively binds to PSMA and is readily incorporated by prostate cancer cells. LW50 was conjugated to a photosensitive compound that, when exposed to the correct wavelength of laser light, released free-radical oxygen molecules that initiated apoptotic destruction of the cancer cells. Specifically they showed that in the cytoplasm of prostate cancer LNCaP cells LW50 photodynamic therapy caused the rapid disruption of microtubules (alpha-/beta-tubulin), microfilaments (actin), and intermediate filaments (cytokeratin 8/18).

"Therapy that is not specifically targeted to cancer cells results in collateral damage,” said senior author Dr. Cliff Berkman, professor of chemistry at Washington State University. "Ultimately, what we're trying to do is cure cancer with light. We will shine light on the tumors and that should cause those cells to self-destruct and the tumors should be eradicated. Once we prove that, then we may have an alternative therapeutic photodrug for the treatment of prostate cancer.”

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