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Photosensitization by 3,3'-Dihexyloxacarbocyanine Iodide: Specific Disruption of Microtubules and Inactivation of Organelle Motility¹

Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115

Photodynamic therapy is a useful new direction for cancer treatment. However, relatively little is currently known about the cellular targets and processes underlying the efficacy of these therapies. In this study, we report evidence of specific photosensitization of a novel intracellular target, cytoskeletal microtubules, that has great importance for cancer treatment. Photosensitization destroys microtubules, halts intracellular organelle motility processes, and leads to rapid cell death. We have examined the cell biological effects of photosensitization with the carbocyanine dye 3,3'-dihexyloxacarbocyanine iodide, which concentrates in mitochondria and the endoplasmic reticulum. Exposure of stained CV-1 kidney epithelial cells to as little as 30–120 s standard fluorescence excitation light caused disruption of the interphase microtubule network and complete inhibition of motility of the endoplasmic reticulum and all phase-contrast visible organelles, as specific effects of dye photoexcitation. Photoexcitation of rhodamine 123 or Hoechst produced neither of these effects. Furthermore, 3,3'-dihexyloxacarbocyanine iodide-mediated photodamage was specific to microtubules; other elements of the cytoskeleton, including vimentin intermediate filaments and actin stress fibers, were unaffected. We have reproduced the photoinactivation of microtubules in vitro with purified microtubule proteins.

¹ This work was supported by NIH Grants HD24926, GM38318, CA19589, CA22427, CA44704, and AI27336.

² Present address: Department of Chemistry, MC 5080, Stanford University, Stanford, CA 94305-5080.

³ To whom requests for reprints should be addressed.

⁴ Present address: Department of Biochemistry, Stanford University Medical Center, Stanford, CA 94305.

Received 12/20/94. Accepted 3/10/95.

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