Staurosporine induces apoptosis in human papillomavirus positive oral cancer cells at G2/M phase by disrupting mitochondrial membrane potential and modulation of cell cytoskeleton.
Our study demonstrates that staurosporine (STS), a protein kinase inhibitor from Streptomyces sp., induces apoptosis in human papillomavirus positive oral carcinoma cells (KB) in a dose dependent manner. Growth inhibition studies revealed an IC(50) value of approximately 100 nM. STS induced marked nuclear fragmentation and inter-nucleosomal cleavage compared to untreated cells. It also caused dose dependent disruption of mitochondrial membrane potential and activation of caspase-3, indicating involvement of mitochondria-mediated cell death signaling in KB cell apoptosis. We found time-dependent arrest of the KB cells at G2/M phase of cell cycle. Using fluorescence microscopy, we have further shown that STS treatment disrupts microtubules and reorganizes F-actin after 6h exposure. Taken together, our results suggest that STS induces mitochondria-mediated KB cell apoptosis at G2/M phase by altering cell cytoskeletal network.
Sarkar
Jayanta
J
Drug Target Discovery and Development Division, Central Drug Research Institute, Lucknow 226 001, India. jayantavirol@gmail.com
Singh
Neetu
N
Meena
Sanjeev
S
Sinha
Sudhir
S
D000199:Actins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects*; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000821:virology; D027383:Papillomaviridae; D019311:Staurosporine / Q000494:pharmacology*
D000199:Actins; D004791:Enzyme Inhibitors; D053148:Caspase 3; D019311:Staurosporine