Apoptotic mechanism of paclitaxel-induced cell death in human head and neck tumor cell lines.
BACKGROUND
Paclitaxel (taxol) is clinically used to treat various human tumors. However, the cellular and molecular mechanism regarding apoptotic effect of paclitaxel on head and neck squamous cell carcinoma (HNSCC) remains elusive.


METHODS
The apoptotic effect and the mechanism of paclitaxel on FaDu hypopharyngeal cancer cell line, OEC-M1 gingival cancer cell line, and OC3 betel quid chewing-related buccal cancer cell lines were investigated by morphological observations, cell viability assay, flow cytometry assay and Western blotting methods.


RESULTS
Rounded-up cell number increased with membrane blebbing as the treatment of paclitaxel (50-500 nM) increased from 24 to 48 h among these cell lines. In cell viability assay, cell surviving rate significantly decreased from 87 to 27% as the dosage and duration of paclitaxel treatment increased (P < 0.05). Flow-cytometry analysis further demonstrated that 50 nM paclitaxel induced G2/M phase cell arrest among these cell lines within 8 h treatment, and then G2/M phase cell fraction significantly decreased as subG1 phase cell fraction significantly increased after 24 h treatment (P < 0.05), suggesting that cells underwent apoptosis. Furthermore, the activated caspases-8, -9, -3, -6 and poly ADP-ribose polymerase cleavage could all be significantly detected in FaDu, OEC-M1 and OC3 cells (P < 0.05).


CONCLUSIONS
Paclitaxel activated cell cycle arrest and caspase protein expressions to induce apoptosis in HNSCC cell lines.
Hsiao
J-R
JR
Department of Otolaryngology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Leu
S-F
SF
Huang
B-M
BM
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000188:drug therapy; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology* / Q000627:therapeutic use; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; D017239:Paclitaxel