Curcumin inhibits the expression of ornithine decarboxylase and adenosine deaminase genes in MCF-7 human breast cancer cells
Keywords:antitumor, breast cancer, cell proliferation, adenosine deaminase (ADA), ornithine decarboxylase 1 (ODC1)
- Curcumin, a multi-target compound, expresses anti-tumor activity in different pathways, including ornithine decarboxylase 1 (ODC1) and adenosine deaminase (ADA) inhibition. The roles of these enzymes have been investigated in curcumin-related studies at the level of enzyme activities; inconclusive experiments have been conducted at the protein expression level.
- In the human breast cancer cell line MCF7, Western blotting and real time PCR revealed downregulation of ODC1 and ADA by curcumin at the transcription level. We concluded that this was the result of reduced gene expression.
- Curcumin could suppress the proliferation of breast cancer cells through downregulation of ODC1 and ADA genes.
Abstract: Curcumin is the active ingredient of Curcuma longa, which inhibits the development of malignant cells. Prevention and treatment of cancer by natural compounds, especially curcumin, and understanding the mechanism of action, is an area of interest in cancer research. In this study, we evaluated the effects of curcumin on cell proliferation, ornithine decarboxylase 1 (ODC1) and adenosine deaminase (ADA) gene expression in human breast cancer cell line (MCF-7) as compared to the non-cancer line (MCF-10A). Both cell lines were subjected to increasing doses of curcumin, ranging from 0 to 30 μg/mL. Cell viability was quantified by the MTT assay. In vitro clonogenic survival assay was performed on MCF-7 cells. Expression of ADA and ODC1 were analyzed by Western blotting and qRT-PCR. Curcumin inhibited the growth of malignant cells in a time- and dose-dependent manner. The calculated IC50 value for MCF-7 cells in 48 h was 12 μg/mL. Forty-five to 70% decreases in colony formation were observed in MCF-7 cells treated with 30-60 μg/mL curcumin, respectively. Our data revealed a dose-dependent downregulation of ODC1 and ADA expression and respective enzyme activities by curcumin, which correlated with decreased proliferation in the MCF-7 breast cancer cell line. These data suggest that curcumin represses the proliferation of breast cancer cells through downregulation of ODC1 and ADA gene expression, which might be another mechanism of curcumin-mediated tumor growth inhibition.
Received: February 9, 2018; Revised: May 21, 2018; Accepted: May 29, 2018; Published online: May 31, 2018
How to cite this article: Abbaspour Hossein, Safipour Afshar A. Curcumin inhibits the expression of ornithine decarboxylase and adenosine deaminase genes in MCF-7 human breast cancer cells. Arch Biol Sci. 2018;70(4):639-45.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7-30.
Ferlay J, Héry C, Autier P, Sankaranarayanan R. Global Burden of Breast Cancer. In: Li C, editor. Breast Cancer Epidemiology. New York, NY: Springer New York; 2010. p.1-19.
Kocaadam B, Sanlier N. Curcumin, an active component of turmeric (Curcuma longa), and its effects on health. Crit Rev Food Sci Nutr. 2017;57:2889-95.
Campbell MS, Fleenor BS. The emerging role of curcumin for improving vascular dysfunction: A review. Crit Rev Food Sci Nutr. 2017:1-10.
Cui T, Zhang S, Sun H. Co-delivery of doxorubicin and pH-sensitive curcumin prodrug by transferrin-targeted nanoparticles for breast cancer treatment. Oncol Rep. 2017;37:1253-60.
Elmegeed GA, Yahya SM, Abd-Elhalim MM, Mohamed MS, Mohareb RM, Elsayed GH. Evaluation of heterocyclic steroids and curcumin derivatives as anti-breast cancer agents: Studying the effect on apoptosis in MCF-7 breast cancer cells. Steroids. 2016;115:80-9.
Berrak O, Akkoc Y, Arisan ED, Coker-Gurkan A, Obakan-Yerlikaya P, Palavan-Unsal N. The inhibition of PI3K and NFkappaB promoted curcumin-induced cell cycle arrest at G2/M via altering polyamine metabolism in Bcl-2 overexpressing MCF-7 breast cancer cells. Biomed Pharmacother. 2016;77:150-60.
Mahajan M, Tiwari N, Sharma R, Kaur S, Singh N. Oxidative stress and its relationship with adenosine deaminase activity in various stages of breast cancer. Indian J Clin Biochem. 2013;28:51-4.
Afshar AS, Nematpour FS, Meshkani M, Khafi A. Growth inhibition of human breast cancer cells and down-regulation of ODC1 and ADA genes by Nepeta binaloudensis. Rev Bras Farmacogn. 2017;27:84-90.
Murray-Stewart TR, Woster PM, Casero RA. Targeting polyamine metabolism for cancer therapy and prevention. Biochem J. 2016;473:2937-53.
Zhu Q, Jin L, Casero RA, Davidson NE, Huang Y. Role of ornithine decarboxylase in regulation of estrogen receptor alpha expression and growth in human breast cancer cells. Breast Cancer Res Treat. 2012;136:57-66.
Cortés A, Gracia E, Moreno E, Mallol J, Lluís C, Canela EI, Casadó V. Moonlighting adenosine deaminase: a target protein for drug development. Med Res Rev. 2015;35:85-125.
Aghaei M, Karami-Tehrani F, Salami S, Atri M. Diagnostic value of adeno-sine deaminase activity in benign and malignant breast tumors. Arch Med Res 2010;41:14–8.
Franken NA, Rodermond HM, Stap J, Haveman J, van Bree C. Clonogenic assay of cells in vitro. Nat Protoc. 2006;1:2315-9.
Ostrowski J, Woszczynski M, Kowalczyk P, Wocial T, Hennig E, Trzeciak L, Janik P, Bomsztyk K. Increased activity of MAP, p70S6 and p90rs kinases is associated with AP-1 activation in spontaneous liver tumours, but not in adjacent tissue in mice. Br J Cancer. 2000;82:1041.
Gupta BK, Bharat A, Debapriya B, Baruah H. Adenosine deaminase levels in CSF of tuberculous meningitis patients. J Clin Med Res. 2010;2:220.
Wang X, Hang Y, Liu J, Hou Y, Wang N, Wang M. Anticancer effect of curcumin inhibits cell growth through miR-21/PTEN/Akt pathway in breast cancer cell. Oncology Lett. 2017;13(6):4825-31.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods. 2001;25:402-8.
Devassy JG, Nwachukwu ID, Jones PJ. Curcumin and cancer: barriers to obtaining a health claim. Nutr Rev. 2015;73:155-65.
Ravindran J, Prasad S, Aggarwal BB. Curcumin and cancer cells: how many ways can curry kill tumor cells selectively?. AAPS J. 2009;11(3):495-510.
Liao YF, Hung HC, Hour TC, Hsu PC, Kao MC, Tsay GJ, Liu GY. Curcumin induces apoptosis through an ornithine decarboxylase-dependent pathway in human promyelocytic leukemia HL-60 cells. Life Sci. 2008;82:367-75.
Jiang M, Huang O, Zhang X, Xie Z, Shen A, Liu H, Geng M, Shen K. Curcumin induces cell death and restores tamoxifen sensitivity in the antiestrogen-resistant breast cancer cell lines MCF-7/LCC2 and MCF-7/LCC9. Molecules. 2013;18:701-20.
Battaglia V, DeStefano Shields C, Murray-Stewart T, Casero RA Jr. Polyamine catabolism in carcinogenesis: potential targets for chemotherapy and chemoprevention. Amino Acids. 2014;46:511-9.
Nowotarski SL, Origanti S, Shantz LM. Posttranscriptional regulation of ornithine decarboxylase. Methods Mol Biol. 2011;720:279-92.
Murray-Stewart TR, Woster PM, Casero RA Jr. Targeting polyamine metabolism for cancer therapy and prevention. Biochem J. 2016;473:2937-53.
Moloney JN, Cotter TG. ROS signalling in the biology of cancer. Semin Cell Dev Biol. 2017;https://doi.org/10.1016/j.semcdb.2017.05.023.
Dai F, Chen WF, Zhou B, Yang L, Liu ZL. Antioxidative effects of curcumin and its analogues against the free-radical-induced peroxidation of linoleic acid in micelles. Phytother Res. 2009;23:1220-8.
Qiao Q, Jiang Y, Li G. Inhibition of the PI3K/AKT-NF-kappaB pathway with curcumin enhanced radiation-induced apoptosis in human Burkitt's lymphoma. J Pharmacol Sci. 2013;121:247-56.
Gracia E, Pérez-Capote K, Moreno E, Barkešová J, Mallol J, Lluís C, Franco R, Cortés A, Casadó V, Canela EI. A2A adenosine receptor ligand binding and signalling is allosterically modulated by adenosine deaminase. Biochem J. 2011;435:701-9.
Gracia E, Farré D, Cortés A, Ferrer-Costa C, Orozco M, Mallol J, Lluís C, Canela EI, McCormick PJ, Franco R, Fanelli F, Casadó V. The catalytic site structural gate of adenosine deaminase allosterically modulates ligand binding to adenosine receptors. Faseb J. 2013;27:1048-61.
Ye JH, Rajendran VM. Adenosine: an immune modulator of inflammatory bowel diseases. World J Gastroenterol. 2009;15:4491-8.
Ohta A. A Metabolic Immune Checkpoint: Adenosine in Tumor Microenvironment. Front Immunol. 2016;7:109.
Pereira MC, Mohammed R, Van Otterlo WA, De Koning CB, Davids H. Evaluation of the Effects of Aminonaphthoquinone Derivatives in Combination with Curcumin Against ER-positive Breast Cancer and Related Tumours. Anticancer Res. 2017;12:6749-59.
How to Cite
Authors grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgment of the work’s authorship and initial publication in this journal.