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Blebbistatin, a myosin inhibitor, is phototoxic to human cancer cells under exposure to blue light.
MedLine Citation:
PMID:  22507270     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. GENERAL SIGNIFICANCE: Our findings offer new possibilities for blebbistatin as a potential anticancer and photodynamic agent.
Authors:
Aliaksandr Mikulich; Simona Kavaliauskiene; Petras Juzenas
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-10
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  -     ISSN:  0006-3002     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Affiliation:
Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello NO-0310 Oslo, Norway; B.I. Stepanov Institute of Physics of the National Academy of Sciences, Nezavisimosti Ave. 68, BY-220072 Minsk, Belarus.
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