Anti-tumor activity of curcumin against androgen-independent prostate cancer cells via inhibition of NF-κB and AP-1 pathway in vitro

Abstract

The anti-tumor activity of curcumin against androgen-independent prostate cancer cells in vitro and the possible mechanism were investigated. After curcumin treatment, the effect of curcumin on the proliferation of prostate cancer PC-3 cells was assessed by CFSE staining. Flow cytometery (FCM) was performed to analyze the cell cycle and the induction of apoptosis of tumor cells. A luciferase reporter gene assay was used to determine the effects of curcumin on the activities of intracellular NF-κB and AP-1 signaling pathways. The results showed curcumin could effectively inhibit the proliferation of PC-3 cells in vitro (P<0.05). Cells were arrested at G₂/M phase. After curcumin treatment, the percentage of apoptotic cells was significantly higher than in control group (P<0.05). The results of the luciferase assay revealed that curcumin selectively inhibited the activities of the NF-κB and AP-1 signaling pathways in PC-3 cells significantly. It was suggested that curcumin could exert anti-tumor activity against androgen-independent prostate cancer cells in vitro by inhibiting cellular proliferation and inducing apoptosis, which was probably contributed to the inhibition of transcription factors NF-κB and AP-1.

Keywords

curcumin / androgen-independent prostate cancer / NF-κB / AP-1

References

[1] CrawfordE.D.. Epidemiology of prostate cancer. Urology, 2003, 62(6): 3-12

[2] DaiB., YeD.W., KongY.Y., et al.. Individualized prostate biopsy strategy for Chinese patients with different prostate-specific antigen levels. Asian J Androl, 2008, 10(2): 325-331

[3] SchutzF.A., OhW.K.. Neoadjuvant and adjuvant therapies in prostate cancer. Urol Clin North Am, 2010, 37(1): 97-104

[4] DoraiT., CaoY.C., DoraiB., et al.. Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate, 2001, 47(4): 293-303

[5] ZeiglerC.M., RennertH., MittalR.D., et al.. Evaluation of prostate cancer characteristics in four populations worldwide. Can J Urol, 2008, 15(3): 4056-4064

[6] ThangapazhamR.L., SharmaA., MaheshwariR.K.. Multiple molecular targets in cancer chemoprevention by curcumin. AAPS J, 2006, 8(3): 443-449

[7] Stacewicz-SapuntzakisM., BorthakurG., BurnsJ.L., et al.. Correlations of dietary patterns with prostate health. Mol Nutr Food Res, 2008, 52(1): 114-130

[8] PeraboF.G., Von LöwE.C., EllingerJ., et al.. Soy isoflavone genistein in prevention and treatment of prostate cancer. Prostate Cancer Prostatic Dis, 2008, 11(1): 6-12

[9] TrumpD.L., DeebK.K., JohnsonC.S.. Vitamin D: considerations in the continued development as an agent for cancer prevention and therapy. Cancer J, 2010, 16(1): 1-9

[10] OhW.K., SmallE.J.. Complementary and alternative therapies in prostate cancer. Semin Oncol, 2002, 29(6): 575-584

[11] AggarwalB.B.. Prostate cancer and curcumin: add spice to your life. Cancer Biol Ther, 2008, 7: 1436-1440

[12] ChendilD., RangaR.S., MeigooniD., et al.. Curcumin confers radiosensitizing effect in prostate cancer cell line PC-3. Oncogene, 2004, 23(8): 1599-1607

[13] CuiS.X., QuX.J., XieY.Y., et al.. Curcumin inhibits telomerase activity in human cancer cell lines. Int J Mol Med, 2006, 18(2): 227-231

[14] KunnumakkaraA.B., AnandP., AggarwalB.B.. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett, 2008, 269(2): 199-225

[15] ClaudioE., SaretS., WangH., et al.. Cell-autonomous role for NF-kappa B in immature bone marrow B cells. J Immunol, 2009, 182(6): 3406-3413

[16] CrispenP.L., UzzoR.G., GolovineK., et al.. Vitamin E succinate inhibits NF-κB and prevents the development of a metastatic phenotype in prostate cancer cells: implications for chemoprevention. Prostate, 2007, 67(6): 582-590

[17] SuhJ., RabsonA.B.. NF-kappa B activation in human prostate cancer: important mediator or epiphenomenon?. J Cell Biochem, 2004, 91(1): 100-117

[18] ZhangL., AltuwaijriS., DengF., et al.. NF-kappaB regulates androgen receptor expression and prostate cancer growth. Am J Pathol, 2009, 175(2): 489-499

[19] MatthewsC.P., ColburnN.H., YoungM.R.. AP-1 a target for cancer prevention. Curr Cancer Drug Targets, 2007, 7(4): 317-324

[20] MukhopadhyayA., Bueso-RamosC., ChatterjeeD., et al.. Curcumin downregulates cell survival mechanisms in human prostate cancer cell lines. Oncogene, 2001, 20(52): 7597-7609

[21] Jacobs-HelberS.M., WickremaA., BirrerM.J., et al.. AP1 regulation of proliferation and initiation of apoptosis in erythropoietin-dependent erythroid cells. Mol Cell Biol, 1998, 18(7): 3699-3707

[22] RippleM.O., HenryW.F., SchwarzeS.R., et al.. Effect of antioxidants on androgen-induced AP-1 and NF-kappaB DNA-binding activity in prostate carcinoma cells. J Natl Cancer Inst, 1999, 91(14): 1227-1232