Lee C, Wu S S, Chen L B
Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Cancer Res. 1995 May 15;55(10):2063-9.
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.
光动力疗法是癌症治疗中一个有用的新方向。然而，目前对于这些疗法疗效背后的细胞靶点和过程了解相对较少。在本研究中，我们报告了一种新型细胞内靶点——细胞骨架微管发生特异性光致敏的证据，这对癌症治疗非常重要。光致敏会破坏微管，阻止细胞内细胞器的运动过程，并导致细胞迅速死亡。我们用集中在线粒体和内质网中的羰花青染料3,3'-二己基氧羰花青碘化物研究了光致敏的细胞生物学效应。将染色的CV-1肾上皮细胞暴露于低至30 - 120秒的标准荧光激发光下，会导致间期微管网络破坏以及内质网和所有相差可见细胞器的运动完全抑制，这是染料光激发的特异性效应。若激发罗丹明123或Hoechst则不会产生这些效应。此外，3,3'-二己基氧羰花青碘化物介导的光损伤对微管具有特异性；细胞骨架的其他成分，包括波形蛋白中间丝和肌动蛋白应力纤维，均未受影响。我们已经在体外使用纯化的微管蛋白重现了微管的光失活。
