Celecoxib in combination with retinoid CD437 inhibits melanoma A375 cell in vitro

Abstract

This study aimed to investigate the effects of celecoxib, synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid (CD437) and the combination of the two on cell proliferation, apoptosis, and cycle arrest of human malignant melanoma A375 cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-di-phenyltetrazoliumbromide assay (MTT assay) was applied to determine the anti-proliferative effects of the drugs on human malignant melanoma A375 cells. Flow cytometry was performed to investigate the influence of the drugs on cell cycle and cell apoptosis. Both celecoxib and CD437 could inhibit the growth of human malignant melanoma A375 cells in a dose-dependent manner. Celecoxib at 80 μmol/L inhibited proliferation, induced apoptosis and G₂/M cell cycle arrest of human malignant melanoma A375 cells after treatment for 24 h [proliferation inhibiting rate: (50.2±2.51)%, apoptosis rate: (35.91±1.80)%]. CD437 at 10 μmol/L inhibited proliferation, induced apoptosis and G₀/G₁ cell cycle arrest of human malignant melanoma A375 cells after treatment for 24 h [proliferation inhibiting rate: (58.6±2.38)%, apoptosis rate: (28.03±0.77)%]. Celecoxib in combination with CD437 could significantly enhance the effects of inhibiting proliferation and inducing apoptosis of human malignant melanoma A375 cells 24 h after treatment compared with the drug alone [proliferation inhibiting rate: (68.92±1.72)%, apoptosis rate: (42.09±1.05)%, both P<0.05] and could decrease the proportion of the S phase in the cell cycle. Celecoxib could inhibit the growth of human malignant melanoma A375 cells by inducing apoptosis and G₂/M cycle arrest. CD437 could inhibit the growth of human malignant melanoma A375 cells by inducing apoptosis and G₀/G₁ cycle arrest. Celecoxib exhibited additive effects with CD437 on retarding the growth and inducing apoptosis of human malignant melanoma A375 cells. Celecoxib in combination with CD437 may become an effective method for prevention and treatment of human melanoma.

Keywords

celecoxib / CD437 / melanoma A375 cell / apoptosis / cycle arrest

References

[1] MericJ B, RotteyS, OlaussenK, SoriaJ C, KhayatD, RixeO, SpanoJ P. Cyclooxygenase-2 as a target for anticancer drug development. Crit Rev Oncol Hematol, 2006, 59(1): 51-64

[2] PatrignaniP, TacconelliS, SciulliM G, CaponeM L. New insights into COX-2 biology and inhibition. Brain Res Brain Res Rev, 2005, 48(2): 352-359

[3] YamadaN, OhiraM, HirakawaK. COX and study of cancer therapy. Gan To Kagaku Ryoho, 2004, 31(8): 1147-1151

[4] FutagamiS, SuzukiK, HiratsukaT, ShindoT, HamamotoT, UekiN, KusunokiM, MiyakeK, GudisK, TsukuiT, SakamotoC. Chemopreventive effect of celecoxib in gastric cancer. Inflammopharmacology, 2007, 15(1): 1-4

[5] AmirM, AgarwalH K. Role of COX-2 selective inhibitors for prevention and treatment of cancer. Pharmazie, 2005, 60(8): 563-570

[6] JohnsonG E, IvanovV N, HeiT K. Radiosensitization of melanoma cells through combined inhibition of protein regulators of cell survival. Apoptosis, 2008, 13(6): 790-802

[7] ChiuL C, TongK F, OoiV E. Cytostatic and cytotoxic effects of cyclooxygenase inhibitors and their synergy with docosahexaenoic acid on the growth of human skin melanoma A-375 cells. Biomed Pharmacother,2005, 59(Suppl 2): S293-S297

[8] GroschS, MaierT J, SchiffmannS, GeisslingerG. Cyclooxygenase-2 (COX-2)-independent anticarcinogenic effects of selective COX-2 inhibitors. J Natl Cancer Inst, 2006, 98(11): 736-747

[9] FarhanaL, DawsonM I, LeidM, WangL, MooreD D, LiuG, XiaZ, FontanaJ A. Adamantyl-substituted retinoid-related molecules bind small heterodimer partner and modulate the Sin3A repressor. Cancer Res, 2007, 67(1): 318-325

[10] GarattiniE, ParrellaE, DiomedeL, GianniM, KalacY, MerliniL, SimoniD, ZanierR, FerraraF F, ChiarucciI, CarminatiP, TeraoM, PisanoC. <patent>ST1926</patent>, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood, 2004, 103(1): 194-207

[11] ZhaoX, DemaryK, WongL, VaziriC, McKenzieA B, EberleinT J, SpanjaardR A. Retinoic acid receptor-independent mechanism of apoptosis of melanoma cells by the retinoid CD437 (AHPN). Cell Death Differ, 2001, 8(9): 878-886

[12] DanielssonC, TormaH, VahlquistA, CarlbergC. Positive and negative interaction of 1,25-dihydroxyvitamin D3 and the retinoid CD437 in the induction of human melanoma cell apoptosis. Int J Cancer, 1999, 81(3): 467-470

[13] ZhangX K. Targeting Nur77 translocation. Expert Opin Ther Targets, 2007, 11(1): 69-79

[14] ZouC, ZhouJ, QianL, FeugangJ M, LiuJ, WangX, WuS, DingH, ZouC, LiebertM, GrossmanH B. Comparing the effect of ATRA, 4-HPR, and CD437 in bladder cancer cells. Front Biosci, 2006, 11: 2007-2016

[15] KimH J, LotanR. Identification of protein modulation by the synthetic retinoid CD437 in lung carcinoma cells using high throughput immunoblotting. Int J Oncol, 2005, 26(2): 483-491

[16] SolaryE, BettaiebA, Dubrez-DalozL, CorcosL. Mitochondria as a target for inducing death of malignant hematopoietic cells. Leuk Lymphoma, 2003, 44(4): 563-574

[17] RishiA K, ZhangL, BoyanapalliM, WaliA, MohammadR M, YuY, FontanaJ A, HatfieldJ S, DawsonM I, MajumdarA P, ReichertU. Identification and characterization of a cell cycle and apoptosis regulatory protein-1 as a novel mediator of apoptosis signaling by retinoid CD437. J Biol Chem, 2003, 278(35): 33422-33435

[18] WatanabeY, TsuchiyaH, SakabeT, MatsuokaS, AkechiY, FujimotoY, YamaneK, IkedaR, NishioR, TerabayashiK, IshiiK, GondaK, MatsumiY, AshlaA A, OkamotoH, TakuboK, TomitaA, HoshikawaY, KurimasaA, ItamochiH, HaradaT, TerakawaN, ShiotaG. CD437 induces apoptosis in ovarian adenocarcinoma cells via ER stress signaling. Biochem Biophys Res Commun, 2008, 366(3): 840-847

[19] JinF, LiuX, ZhouZ, YueP, LotanR, KhuriF R, ChungL W, SunS Y. Activation of nuclear factor-kappaB contributes to induction of death receptors and apoptosis by the synthetic retinoid CD437 in DU145 human prostate cancer cells. Cancer Res, 2005, 65(14): 6354-6363

[20] KadaraH, SchroederC P, LotanD, PisanoC, LotanR. Induction of GDF-15/NAG-1/MIC-1 in human lung carcinoma cells by retinoid-related molecules and assessment of its role in apoptosis. Cancer Biol Ther, 2006, 5(5): 518-522

[21] HolmesW F, SopranoD R, SopranoK J. Synthetic retinoids as inducers of apoptosis in ovarian carcinoma cell lines. J Cell Physiol, 2004, 199(3): 317-329

[22] ZhaoX, SpanjaardR A. The apoptotic action of the retinoid CD437/AHPN: diverse effects, common basis. J Biomed Sci, 2003, 10(1): 44-49

Acknowledgements

This study was supported by the National Natural Science Foundation of China (Grant No. 30371295).

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg