4-(2-(5-6-7-8-tetrahydro-5-5-8-8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic-acid and Carcinoma--Squamous-Cell

To investigate the receptor-related mechanism of retinoids inhibiting proliferation and inducing apoptosis of human oral squamous cell carcinoma cell line Tca8113.. The effects of 3 retinoids (namely 9-cis-RA, at-RA and 13-cis-RA), TTNPB (RAR agonist) and methoprene acid (Ma, RXR agonist) on proliferation and cell cycle of Tca8113 cells were analyzed by MTT assay and flow cytometry. The roles of these agents in inducing apoptosis of Tca8113 cells were also evaluated by detecting the expression of Bcl-2/Bax, TUNEL and active caspase-3 analysis.. Both retinoids and TTNPB could inhibit the proliferation of Tca8113 cells, and the effect of TTNPB was the most powerful in all the reagents, but MA had no such effect. At the concentration of 1 x 10(-5) mol/L, all the agents except for Ma could increase the percentage of G(1)/G(0)-stage cells after incubation of the cells for 24 h and 48 h. Retinoids and TTNPB could up-regulate the expression of Bax and down-regulate Bcl-2 expression. The results of TUNEL demonstrated that retinoids and TTNPB, but not Ma, could induce apoptosis of Tca8113 cells as compared with the control group (P<0.05). Except for Ma, all the agents up-regulated caspase-3 expression, and the effect of TTNPB was the strongest (P<0.05).. Retinoids can suppress the proliferation of and induce apoptosis of Tca8113 cells, the effect of which involves activation of RAR but not RXR. caspase-3 pathway is involved in apoptosis-inducing effects of retinoids.

Topics: Antineoplastic Agents; Apoptosis; Benzoates; Carcinoma, Squamous Cell; Cell Line, Tumor; Humans; Receptors, Retinoic Acid; Retinoids; Tongue Neoplasms; Tretinoin

The human keratinocyte line SCC-4 is a model system in which to explore the mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) interferes with the action of hormones in the steroid receptor superfamily. In present work, retinoid induction of tissue transglutaminase mRNA was suppressed 60-70% by 10 nM TCDD in the human squamous carcinoma cell line SCC-4. This effect occurred without enhanced degradation of the mRNA and thus appeared to result from altered transcription. The actions of all-trans-retinoic acid and the synthetic retinoid TTNPB ((E)4-[2-(5,6,7,8-tetrahydro-5,5,8, 8-tetramethyl-2-naphthylenyl)-1propenyl] benzoic acid), which resists metabolic degradation, were suppressed to the same extent without obvious changes in their EC(50)s. In addition, TCDD suppression of reporter transcription, driven by a retinoic acid response element, was not evident in transient or stable transfections of SCC-4 cells. Sodium butyrate (3 mM) alone induced tissue transglutaminase and augmented retinoid induction. In the presence of butyrate, TCDD acted as an inducer and did not reduce retinoid stimulation. Retinoic acid induction of tissue transglutaminase displayed a lag phase of >24 h, indicating that the induction has an indirect component. Rather than depleting active retinoid in the culture medium or generally inactivating retinoid receptor function, TCDD may suppress retinoid action in this case by interfering with the late phase of induction.

Topics: Benzoates; Carcinoma, Squamous Cell; Humans; Keratinocytes; Polychlorinated Dibenzodioxins; Retinoids; RNA, Messenger; Transglutaminases; Tretinoin; Tumor Cells, Cultured

The aim of this study was to evaluate the effect of four natural and synthetic retinoids: Ro 12-7310 (I), Ro 13-7410 (II), 13-cis-retinoic acid (III), and Ro 13-7652 (IV) on the synthesis of PGE2 in human squamous cell carcinoma (SCC) of the tongue (SCC-25). 5 X 10(6) cells were plated and labeled with 0.2 microCi of (14C)-arachidonic acid (AA) in 2 ml of DMEM/F12 containing 0.1% BSA for 4 h. The cells were then washed, and incubated in serum-free medium with the retinoids (10,20,30,40 microM) for 1 h. The cells were further stimulated with melittin an additional hour. Radioactive metabolites released in media were then extracted with diethyl ether. The ether extracts were separated by TLC and radioactive PGE2 zone was quantitated by means of liquid scintillation counting. The rank order of percent inhibition of PGE2 synthesis by retinoids at four concentration levels was (I) greater than (II) greater than (III) greater than (IV). Since inhibition of PG production has been demonstrated to suppress growth of tumors in animal models and humans, further study on the effect of retinoids on growth of SCC in vitro as well as in vivo seems warranted.

Topics: Acitretin; Arachidonic Acid; Arachidonic Acids; Benzoates; Carcinoma, Squamous Cell; Dinoprostone; Dose-Response Relationship, Drug; Etretinate; Humans; Prostaglandin-Endoperoxide Synthases; Retinoids; Tongue Neoplasms; Tretinoin; Tumor Cells, Cultured