RESUMO
The effect of indomethacin, cisplatin and delta 12-prostaglandin J2 (PGJ2) on the inhibition of cell growth and DNA Synthesis (i.e. cell proliferation), was evaluated in vitro on human oral squamous carcinoma cells(SCC-25). The rank order of their inhibitory potency at 10(-5) M was delta 12-PGJ2 > cisplatin > indomethacin. However, delta 12-PGJ2 at 10(-7) and 10(-6) M induced a significant stimulatory effect on cell growth as well as DNA synthesis. The sefindings suggest that delta 12-PGJ2 is a promising novel chemotherapeutic agent for oral cancer and potential candidate for future clinical investigations.
Assuntos
Divisão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/toxicidade , Indometacina/toxicidade , Prostaglandina D2/análogos & derivados , Carcinoma de Células Escamosas , DNA de Neoplasias/biossíntese , Relação Dose-Resposta a Droga , Humanos , Prostaglandina D2/toxicidade , Prostaglandinas Sintéticas/toxicidade , Neoplasias da Língua , Células Tumorais CultivadasRESUMO
Dietary levels of vitamins C and E have been associated with cancer prevention and to a lesser extent with therapeutic enhancement of cancer treatment. Inhibition of prostaglandins (PGs) by pharmacological agents has been demonstrated to enhance immunocompetence, and to suppress growth of tumors in animals and humans. We report here on the effect of vitamins C and E on PGE2 production by human gingival fibroblasts and SCC-25 oral squamous carcinoma cells. The results indicate: 1. vitamins C and E exert a dose-dependent effect on arachidonic acid (AA) release and PGE2 synthesis; 2. vitamin E has a biphasic effect which is stimulatory at 1 and 10 microM and inhibitory at 100 microM; 3. vitamin E is considerably more potent than vitamin C in its inhibitory effect on AA and PGE2 in both cell types; 4. a combination of the two vitamins has a consistent dose-dependent inhibitory effect on AA and PGE2; 5. vitamin C stimulates PGE2 synthesis from exogenous AA in fibroblasts, and inhibits it in SCC-25 cells. The in vivo significance of these findings requires further investigation.
Assuntos
Ácido Ascórbico/farmacologia , Carcinoma de Células Escamosas/metabolismo , Dinoprostona/biossíntese , Fibroblastos/metabolismo , Vitamina E/farmacologia , Adulto , Ácido Araquidônico/antagonistas & inibidores , Ácido Araquidônico/metabolismo , Linhagem Celular , Feminino , Fibroblastos/efeitos dos fármacos , Gengiva/citologia , Humanos , Neoplasias da Língua/metabolismo , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
The purpose of this study was to determine the nature and amounts of prostaglandins (PGs) produced by squamous carcinoma cells (SCC) and the sensitivity of these cells to non-steroidal anti-inflammatory drugs. SCC of four lines of the tongue and one line of facial epidermis of humans were incubated in phosphate buffer solution with 14C-arachidonic acid (AA). Radioactive metabolites in aqueous methanol were chromatographed on Sep-Pack C18 cartridges, separated and quantitated by means of TLC, autoradiography, and liquid scintillation counting. The results showed that cyclooxygenase products, PGs, were the major products formed by all cell lines, and PGE2 was predominant among the PGs detected. Two radioactive bands corresponding to PGF2 alpha and three unseparated standards of PGA2, 15-keto-PGE2, and 13,14-dihydro-15-keto-PGE2 were detected in lesser amounts. Very small amounts of the lipoxygenase products 12- and 15-HETE were found. The concentrations of indomethacin, ibuprofen and aspirin required to inhibit 50% of PGE2 synthesis (IC50) by SCC lines were .008-.080, .080-6.4 and 32-88 microM, respectively.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Carcinoma de Células Escamosas/metabolismo , Antagonistas de Prostaglandina , Prostaglandinas/biossíntese , Ácidos Araquidônicos/metabolismo , Aspirina/farmacologia , Linhagem Celular , Dinoprostona , Neoplasias Faciais , Humanos , Ibuprofeno/farmacologia , Indometacina/farmacologia , Prostaglandinas E/antagonistas & inibidores , Prostaglandinas E/biossíntese , Neoplasias da LínguaRESUMO
The metabolism of [14C]arachidonic acid into cyclooxygenase and lipoxygenase products by homogenates of primary squamous carcinomas of head and neck in 12 patients was studied in vitro. The lipoxygenase pathway was predominant in all samples. The major metabolites were 12-hydroxy-5,8,11-14-eicosatetraenoic acid, (12-HETE) and 15-HETE. 5-HETE, 5,12-diHETE, 8-HETE and 9-HETE were also detected. The cyclooxygenase products detected were in the following order: PGE2 greater than PGF2 alpha greater than TxB2 greater than 15-keto-PGE2 greater than 6-keto-PGF1 alpha greater than PGD2. Literature review of the biological activities of these oxygenated metabolites of arachidonic acid suggest important modulatory roles in the pathophysiology of head and neck cancer.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Hidroxiácidos/biossíntese , Prostaglandinas/biossíntese , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico , Humanos , Ácidos Hidroxieicosatetraenoicos/metabolismoRESUMO
The present study shows that 14C-arachidonic acid metabolism in gingiva of patients with periodontal disease is mainly via the lipoxygenase pathway. In two pools of gingival tissue homogenates, the lipoxygenase products contained 22.65% and 23.38%, while the prostaglandins (PGs), products of the cyclooxygenase pathway, contained only 4.85% and 3.98% of the total radioactivity incubated. 12-hydroxy-eicosatetraenoic acid (12-HETE), a lipoxygenase product, was detected as a major metabolite of arachidonic acid in gingiva.
