title: Apoptosis induction and enhancement of cytotoxicity of anticancer drugs by celecoxib, a selective cyclooxygenase-2 inhibitor, in human head and neck carcinoma cell lines.
abstract: Colorectal carcinomas are well known to highly express COX-2 and their growth is markedly inhibited by COX-2 inhibitors, but little is known about head and neck carcinomas. In this study, we investigated the effect of a selective COX-2 inhibitor, celecoxib, on growth and apoptosis induction of four human head and neck carcinoma cell lines, SCC25, KB, HSG and HSY, in comparison with frequently used COX inhibitor sulindac. Also, we examined whether celecoxib augments the sensitivity of these cell lines to anticancer drugs such as doxorubicin (DOX), vincristine (VCR), cisplatin (CDDP), bleomycin (BLM) and 5-fluorouracil (5-FU). The growth of all cultured cell lines particularly SCC25 and HSG was inhibited by celecoxib and sulindac in a dose-dependent manner. The IC50 of celecoxib was ten times lower than that of sulindac. SCC25 produced ample PGE2 whereas KB, HSG and HSY produced a small amount of PGE2. The PGE2 production and COX-2 expression were inhibited more efficiently by celecoxib than by sulindac. Exogenous addition of PGE2 resulted in an increased cell growth of SCC25 even under the celecoxib-treated condition, but not of HSG. These results suggested that PGE2 is involved in the growth of SCC25 but not of HSG. The ability of celecoxib to induce apoptosis is greater than that of sulindac. Treatment of SCC25 and HSG with non-cytotoxic 1 micro M or less cytotoxic 5 micro M of celecoxib enhanced the sensitivity of both cell lines to anticancer drugs, particularly in DOX, VCR and BLM two to ten times as demonstrated by lowering of IC50s. The enhanced rate was almost parallel to the degree of apoptosis induction. These findings indicated that a selective COX-2 inhibitor celecoxib inhibits cell proliferation, induces apoptosis and augments sensitivity to anticancer drugs in human head and neck carcinoma cells. Therefore, celecoxib would be useful as biological modulator in treatment of head and neck cancer.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Hashitani
authors.forename: Masahiro
authors.initials: M
authors.lastname: Urade
authors.forename: Norihiko
authors.initials: N
authors.lastname: Nishimura
authors.forename: Tsunenari
authors.initials: T
authors.lastname: Maeda
authors.forename: Kazuki
authors.initials: K
authors.lastname: Takaoka
authors.forename: Kazuma
authors.initials: K
authors.lastname: Noguchi
authors.forename: Kazunari
authors.initials: K
authors.lastname: Sakurai
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D001761:Bleomycin / Q000494:pharmacology; D015153:Blotting, Western; D002277:Carcinoma / Q000188:drug therapy*; D000068579:Celecoxib; D045744:Cell Line, Tumor; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D053938:DNA Fragmentation; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D013449:Sulfonamides / Q000494:pharmacology*; D013467:Sulindac / Q000494:pharmacology; D013997:Time Factors; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D001761:Bleomycin; D013467:Sulindac; D014750:Vincristine; D004317:Doxorubicin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D015232:Dinoprostone; D002945:Cisplatin; D005472:Fluorouracil