JBM  Vol.7 No.5 , May 2019
The Inhibitory Effect of Curcumin on Ornithine Decarboxylase against Hepatic Carcinoma
Abstract: Curcumin the active component of turmeric is widely used as an anticancer agent for treating many human cancers. This study aimed at the extraction of curcumin from Curcuma Longa and investigates its therapeutic effect as ornithine decarboxylase (ODC) inhibitor in HepG2 cells. The proliferation of HepG2 cells was carried out by using the MTT assay. In addition, cell cycle analysis was evaluated by using the flow-cytometric technique. Our results showed that curcumin has the ability to inhibit the proliferation of HepG2 cells with IC50 of 24.79 μg/ml and induced G2/M cell cycle arrest. Moreover, it caused an elevation in the intracellular concentration of Ca2+. Moreover, in the curcumin administration the downregulation expression level of ODC and Bcl-2 genes (p ≤ 0.05) was significant found. On the other hand, upregulation in the expression level of P53, Bax, and caspase-3 genes (p ≤ 0.05). This study concluded that curcumin may be considered as a new saving candidate for the future progress of antitumor agents.
Cite this paper: Khamis, A. , Sharshar, A. , Mahmoud, A. and Mohamed, T. (2019) The Inhibitory Effect of Curcumin on Ornithine Decarboxylase against Hepatic Carcinoma. Journal of Biosciences and Medicines, 7, 127-145. doi: 10.4236/jbm.2019.75015.

[1]   Migliore, L. and Coppede, F. (2002) Genetic and Environmental Factors in Cancer and Neurodegenerative Diseases. Mutation Research, 512, 135-153.

[2]   Yu, C., et al. (2016) An Updated Dose-Response Meta-Analysis of Coffee Consumption and Liver Cancer Risk. Scientific Reports, 6, Article No. 37488.

[3]   Blonski, W. (2010) Non-Viral Causes of Hepatocellular Carcinoma. World Journal of Gastroenterology, 16, 3603-3615.

[4]   Lin, S., Hoffmann, K. and Schemmer, P. (2012) Treatment of Hepatocellular Carcinoma: A Systematic Review. Liver Cancer, 1, 144-158.

[5]   Befeler, A.S. and di Bisceglie, A.M. (2002) Hepatocellular Carcinoma: Diagnosis and Treatment. Gastroenterology, 122, 1609-1619.

[6]   Safarzadeh, E., Sandoghchian Shotorbani, S. and Baradaran, B. (2014) Herbal Medicine as Inducers of Apoptosis in Cancer Treatment. Advanced Pharmaceutical Bulletin, 4, 421-427.

[7]   Shanmugam, M.K., et al. (2015) The Multifaceted Role of Curcumin in Cancer Prevention and Treatment. Molecules, 20, 2728-2769.

[8]   Teiten, M.H., et al. (2010) Curcumin—The Paradigm of a Multi-Target Natural Compound with Applications in Cancer Prevention and Treatment. Toxins (Basel), 2, 128-162.

[9]   Tayyem, R.F., et al. (2006) Curcumin Content of Turmeric and Curry Powders. Nutrition and Cancer, 55, 126-131.

[10]   Wilken, R., et al. (2011) Curcumin: A Review of Anti-Cancer Properties and Therapeutic Activity in Head and Neck Squamous Cell Carcinoma. Molecular Cancer, 10, 12.

[11]   Lv, F.H., et al. (2016) Effects of Curcumin on the Apoptosis of Cardiomyocytes and the Expression of NF-kappaB, PPAR-Gamma and Bcl-2 in Rats with Myocardial Infarction Injury. Experimental and Therapeutic Medicine, 12, 3877-3884.

[12]   Perrone, D., et al. (2015) Biological and Therapeutic Activities, and Anticancer Properties of Curcumin. Experimental and Therapeutic Medicine, 10, 1615-1623.

[13]   Chiu, T.L. and Su, C.C. (2009) Curcumin Inhibits Proliferation and Migration by Increasing the Bax to Bcl-2 Ratio and Decreasing NF-kappaBp65 Expression in Breast Cancer MDA-MB-231 Cells. International Journal of Molecular Medicine, 23, 469-475.

[14]   Choudhuri, T., et al. (2002) Curcumin Induces Apoptosis in Human Breast Cancer Cells through p53-Dependent Bax Induction. FEBS Letters, 512, 334-340.

[15]   Pegg, A.E. (2006) Regulation of Ornithine Decarboxylase. The Journal of Biological Chemistry, 281, 14529-14532.

[16]   Mohan, R.R., et al. (1999) Overexpression of Ornithine Decarboxylase in Prostate Cancer and Prostatic Fluid in Humans. Clinical Cancer Research, 5, 143-147.

[17]   Kahana, C. (2009) Regulation of Cellular Polyamine Levels and Cellular Proliferation by Antizyme and Antizyme Inhibitor. Essays in Biochemistry, 46, 47-61.

[18]   Liao, Y.F., et al. (2008) Curcumin Induces Apoptosis through an Ornithine Decarboxylase-Dependent Pathway in Human Promyelocytic Leukemia HL-60 Cells. Life Sciences, 82, 367-375.

[19]   Okazaki, Y., Iqbal, M. and Okada, S. (2005) Suppressive Effects of Dietary Curcumin on the Increased Activity of Renal Ornithine Decarboxylase in Mice Treated with a Renal Carcinogen, Ferric Nitrilotriacetate. Biochimica et Biophysica Acta, 1740, 357-366.

[20]   Kulkarni, S., et al. (2012) Extraction and Purification of Curcuminoids from Turmeric (Curcuma longa L.). International Journal of Pharmacology and Pharmaceutical Technology, 1, 81-84.

[21]   Lestari, H., et al. (2017) Simultaneous Analysis of Curcumin and Demethoxycurcumin in Curcuma xanthorriza Using FTIR Spectroscopy and Chemometrics. International Food Research Journal, 24, 2097-2101.

[22]   Molyneux, P. (2004) The Use of the Stable Free Radical Diphenylpicrylhydrazyl (DPPH) for Estimating Antioxidant Activity. Songklanakarin Journal of Science and Technology, 26, 211-219.

[23]   Jiang, J., et al. (2013) Curcumin Disturbed Cell-Cycle Distribution of HepG2 Cells via Cytoskeletal Arrangement. Scanning, 35, 253-260.

[24]   Livak, K.J. and Schmittgen, T.D. (2001) Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25, 402-408.

[25]   Macotpet, A., et al. (2013) Oxidative Stress in Cancer-Bearing Dogs Assessed by Measuring Serum Malondialdehyde. BMC Veterinary Research, 9, 101.

[26]   Weydert, C.J. and Cullen, J.J. (2010) Measurement of Superoxide Dismutase, Catalase and Glutathione Peroxidase in Cultured Cells and Tissue. Nature Protocols, 5, 51-66.

[27]   Aebi, H. (1984) Catalase in Vitro. Methods in Enzymology, 105, 121-126.

[28]   Paglia, D.E. and Valentine, W.N. (1967) Studies on the Quantitative and Qualitative Characterization of Erythrocyte Glutathione Peroxidase. The Journal of Laboratory and Clinical Medicine, 70, 158-169.

[29]   Zhang, H.H., et al. (2018) Metformin in Combination with Curcumin Inhibits the Growth, Metastasis, and Angiogenesis of Hepatocellular Carcinoma in Vitro and in Vivo. Molecular Carcinogenesis, 57, 44-56.

[30]   Chang, M., Wu, M. and Li, H. (2017) Curcumin Combined with Glycyrrhetinic Acid Inhibits the Development of Hepatocellular Carcinoma Cells by Down-Regulating the PTEN/PI3K/AKT Signalling Pathway. American Journal of Translational Research, 9, 5567-5575.

[31]   Shariati, M., et al. (2017) Nanocurcumin-Mediated Down-Regulation of Telomerase via Stimulating TGFbeta1 Signaling Pathway in Hepatocellular Carcinoma Cells. Iranian Biomedical Journal, 22, 171-179.

[32]   Gallardo, M. and Calaf, G.M. (2016) Curcumin and Epithelial-Mesenchymal Transition in Breast Cancer Cells Transformed by Low Doses of Radiation and Estrogen. International Journal of Oncology, 48, 2534-2542.

[33]   Lee, D.S., Lee, M.K. and Kim, J.H. (2009) Curcumin Induces Cell Cycle Arrest and Apoptosis in Human Osteosarcoma (HOS) Cells. Anticancer Research, 29, 5039-5044.

[34]   Zhu, Y. and Bu, S. (2017) Curcumin Induces Autophagy, Apoptosis, and Cell Cycle Arrest in Human Pancreatic Cancer Cells. Evidence-Based Complementary and Alternative Medicine, 2017, Article ID: 5787218.

[35]   Das, L. and Vinayak, M. (2015) Long Term Effect of Curcumin in Restoration of Tumour Suppressor p53 and Phase-II Antioxidant Enzymes via Activation of Nrf2 Signalling and Modulation of Inflammation in Prevention of Cancer. PLoS ONE, 10, e0124000.

[36]   Li, W., et al. (2015) A Preliminary Study of the Effect of Curcumin on the Expression of p53 Protein in a Human Multiple Myeloma Cell Line. Oncology Letters, 9, 1719-1724.

[37]   Chen, H.W. and Huang, H.C. (1998) Effect of Curcumin on Cell Cycle Progression and Apoptosis in Vascular Smooth Muscle Cells. British Journal of Pharmacology, 124, 1029-1040.

[38]   Khazaei Koohpar, Z., et al. (2015) Anticancer Activity of Curcumin on Human Breast Adenocarcinoma: Role of Mcl-1 Gene. Iranian Journal of Cancer Prevention, 8, e2331.

[39]   Jiang, A.J., et al. (2015) Curcumin Induces Apoptosis through Mitochondrial Pathway and Caspases Activation in Human Melanoma Cells. Molecular Biology Reports, 42, 267-275.

[40]   Song, G., et al. (2005) Curcumin Induces Human HT-29 Colon Adeno-carcinoma Cell Apoptosis by Activating p53 and Regulating Apoptosis-Related Protein Expression. Brazilian Journal of Medical and Biological Research, 38, 1791-1798.

[41]   Huang, Y.F., et al. (2017) Curcumin Enhances the Effects of Irinotecan on Colorectal Cancer Cells through the Generation of Reactive Oxygen Species and Activation of the Endoplasmic Reticulum Stress Pathway. Oncotarget, 8, 40264-40275.

[42]   Xu, X., et al. (2015) Curcumin Induces the Apoptosis of Non-Small Cell Lung Cancer Cells through a Calcium Signaling Pathway. International Journal of Molecular Medicine, 35, 1610-1616.

[43]   Giorgi, C., et al. (2012) Mitochondrial Ca2+ and Apoptosis. Cell Calcium, 52, 36-43.