blister and Prostatic-Neoplasms

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 (390-470 nm). 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 10-200 μmol/L was toxic to all studied cells. Toxic concentrations (TC) were about 10-25 μmol/L corresponding to TC10, 50-100 μmol/L to TC50 and 140-190 μmol/L to TC90. Only for the U87 glioma cells TC90 could not be measured as the highest studied concentration of 200 μmol/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.

Topics: Apoptosis; Cell Movement; Cell Survival; Heterocyclic Compounds, 4 or More Rings; Humans; Light; Male; Myosins; Oxidation-Reduction; Photosensitizing Agents; Prostatic Neoplasms; Reactive Oxygen Species; Tumor Cells, Cultured

The migration of cells is a complex regulatory process which results in the generation of motor forces through the reorganization of the cytoskeleton. Here we present a comparative study of the expression and involvement of myosin in the regulation of the physiological migration of leukocytes and the pathological migration of tumor cells. We show that the involvement of myosin in the migration is distinct in these two cell types. In leukocytes, the activity of non-muscle myosin II is essential for both the spontaneous (matrix-induced) migration and the migration induced by ligands to G protein-coupled receptors, i.e. chemokines and neurotransmitters. In contrast, spontaneous tumor cell migration is largely independent of non-muscle myosin II activity, whereas the norepinephrine-induced migration is completely inhibited by either direct inhibition of non-muscle myosin II or of the kinases phosphorylating the myosin light chain, namely ROCK or the calcium/calmodulin-dependent myosin light-chain kinase.

Topics: Actins; Breast Neoplasms; Cell Movement; Collagen; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Intracellular Signaling Peptides and Proteins; Leukocytes; Male; Myosin Type II; Myosin-Light-Chain Kinase; Norepinephrine; Phosphorylation; Prostatic Neoplasms; Protein Isoforms; Protein Serine-Threonine Kinases; rho-Associated Kinases; T-Lymphocytes, Cytotoxic; Tumor Cells, Cultured