Blebbistatin, a myosin inhibitor, is phototoxic to human cancer cells under exposure to blue light

• Published in: Biochimica et biophysica acta 2012-07, Vol.1820 (7), p.870-877
• Main Authors: Mikulich, Aliaksandr, Kavaliauskiene, Simona, Juzenas, Petras
• Format: Article
• Language: English
• Subjects: adenocarcinoma; antineoplastic agents; Apoptosis - drug effects; blue light; cell movement; Cell Movement - drug effects; Cell Survival - drug effects; cytokinesis; cytotoxicity; fibroblasts; Free radical; Heterocyclic Compounds, 4 or More Rings - pharmacology; human cell lines; Humans; irradiation; Light; Male; melanoma; myosin; Myosins - antagonists & inhibitors; Myosins - metabolism; neoplasm cells; Oxidation-Reduction; Photodynamic therapy (PDT); Photosensitization; Photosensitizing Agents - pharmacology; photostability; phototoxicity; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Reactive oxygen species (ROS); Reactive Oxygen Species - metabolism; Scavenger; Singlet oxygen; Tumor Cells, Cultured; viability
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2012.04.003

Blebbistatin is a new inhibitor of cell motility. It is used to study dynamics of cytokinesis machinery in cells. However, the potential of this inhibitor as an anticancer agent has not been studied so far. Cytotoxicity of blebbistatin was evaluated in five human cell lines, FEMX-I melanoma, U87 glioma, androgen independent Du145 and androgen sensitive LNCaP prostate adenocarcinoma, and F11-hTERT immortalized fibroblasts. Phototoxicity of blebbistatin was assessed in these cell lines after their exposure to a blue light (390–470nm). Photostability of blebbistatin and its reactive oxygen species (ROS) generating properties were measured during irradiation with the blue light. Blebbistatin at a concentration range of 10–200μmol/L was toxic to all studied cells. Toxic concentrations (TC) were about 10–25μmol/L corresponding to TC10, 50–100μmol/L to TC50 and 140–190μmol/L to TC90. Only for the U87 glioma cells TC90 could not be measured as the highest studied concentration of 200μmol/L gave around 70% toxicity. However, after exposure to the blue light blebbistatin exhibited phototoxicity on the cells, with a cytotoxicity enhancement ratio that was greatest for the FEMX-I cells (about 9) followed by LNCaP (5), Du145 (3), U87 (2) and F11-hTERT (1.7) cells. Blebbistatin inhibits cell motility and viability. Under exposure to the blue light blebbistatin exhibits photodynamic action on human cancer cells. During the irradiation blebbistatin oxidizes dihydrorhodamine 123 but not Singlet Oxygen Sensor Green. Our findings offer new possibilities for blebbistatin as a potential anticancer and photodynamic agent. ► The study shows blebbistatin as a potential photodynamic drug to kill cancer cells. ► Extent of the photodynamic effect varies for different cell lines. ► During light exposure blebbistatin generates ROS but not singlet oxygen. ► Blebbistatin is photodegraded along with the formation of its photoproducts.