Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, Uttar Pradesh, India
Keywords:
Decoction, synergistic activity, lactate dehydrogenase, hypoxia, metabolismAbstract
Lactic acid fermentation and not oxidative phosphorylation is reported to be one of the major bioenergetics mechanisms by which cancer cells thrive and proliferate with such rapidity in non-ambient hypoxic conditions. The objective of the study was to determine the synergistic effect of spices in a decoction; Turmeric (Curcuma longa), Pepper (Piper nigrum) and Garlic (Allium sativum) in combination, on the metabolism of Hep G2 liver cancer cells.The biochemical studies of 2 major enzymes involved in cellular metabolism of cells namely; Pyruvate dehydrogenase (PDH) and Lactate dehydrogenase A (LDHA) showed that the decoction down regulated the activity of LDHA and increased the activity of PDH in cancer cells, thereby shifting the metabolic mechanism towards normal functioning in the cancer cells. The expression studies of major molecules involved in regulating metabolic machinery in cells viz., tumour suppressor p53 and oncogene MYC mRNAs; and western blot analysis of Hypoxia inducible factor-1-alpha (HIF-1α) and Vascular endothelial growth factor (VEGF) showed that the decoction regulated the expression of these factors helping to revert the metabolism in cancer cells, which could be attributed to the effect of turmeric and also garlic, rich in pantothenic acid, that aids in turning on oxidative phosphorylation in cancer cells. With the above results, it could be concluded that the decoction alters the metabolic mechanism in a cancer cell from lactic acid fermentation to oxidative phosphorylation, like in any other normal cell, thus inhibiting further growth of the cancer.
References
. Ryan HE, Poloni M, McNulty W, Elson D, Gassmann M, Arbeit JM, Johnson RS. Hypoxia-inducible factor-1alpha is a positive factor in solid tumor growth. Cancer Res 2000; 60: 4010-4015.
. Greco O, Marples B, Joiner MC, Scott SD. How to overcome (and exploit) tumor hypoxia for targeted gene therapy. J Cell Physiol 2003; 197: 312-325.
. Zhou Y, Lin L, Wang Y, Jin X, Zhao X, Liu D, Hu T, Jiang L, Dan H, Zeng X, Li j, Wang J, Chen Q. The association between hypoxia-inducible factor-1 alpha gene G1790A polymorphism and cancer risk: a meta-analysis of 28 casecontrol studies. Cancer Cell Int 2014; 14: 37-47.
. Wang GL, Semenza GL. Purification and characterization of hypoxia-inducible factor 1. J Biol Chem 1995; 270: 1230–1237.
. Dery MA, Michaud MD, Richard DE. Hypoxia-inducible factor 1: regulation by hypoxic and non-hypoxic activators. Int J Biochem Cell Biol 2005; 37: 535–540.
. Demain AL, Vaishnav P. Natural products for cancer chemotherapy. Microbial biotechnology 2010; 4: 687-699.
. Bae MK, Kim SH, Jeong JW, Lee YM, Kim HS, Kim SR, Yun I, Bae SK, Kim KW. Curcumin inhibits hypoxia-induced angiogenesis via downregulation of HIF-1. Oncol Rep 2006; 15: 1557–1562.
. Prabhu A, Sarcar B, Kahali S, Yuan Z, Johnson JJ, Adam KP, Kensicki E, Chinnaiyan P. Cysteine catabolism: a novel metabolic pathway contributing to glioblastoma growth. Cancer Res 2014; 74: 787-796.
. Wang Z, Wang D, Han S, Wang N, Mo F, Loo TY, Shen J, Huang H, Chen J. Bioactivity-Guided Identification and Cell Signaling Technology to Delineate the Lactate Dehydrogenase A Inhibition Effects of Spatholobus suberectus on Breast Cancer. PLoS ONE 2013; 8: e56631-e56642.
. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65: 55–63.
. Hans-Joachim D, Annette D, Gr€unewald-Janho ED, Joe SK. PCR Applications Manual (3rd ed.). Roche Diagnostics, Mannheim, Germany. (2006).
. Xi L, Nicastri DG, El-Hefnawy T, Hughes SJ, Luketich JD, Godfrey TE. Optimal markers for real-time quantitative reverse transcription PCR detection of circulating tumor cells from melanoma, breast, colon, esophageal, head and neck, and lung cancers. Clin Chem 2007; 53: 1206–1215.
. Sambrook J, Fritsch EF, Maniatis T. Molecular Cloning: a laboratory manual (2nd ed.) Cold Spring Harbor Laboratory, NY: Cold Spring Harbor Laboratory Press, USA. (1989).
. Eslami A, Lujan J. Western blotting: sample preparation to detection. J Vis Exp 2010; 44: 2359-2360.
. Jang M, Kim SS, Lee J. Cancer cell metabolism: implications for therapeutic targets. Exp Mol Med 2013; 45: e45-e52.
. Gupta SC, Patchva S, Koh W, Aggarwal BB. Discovery of curcumin, a component of golden spice, and its miraculous biological activities. Clin Exp Pharmacol Physiol 2012; 39: 283-299.
. Wilken R, Veena MS, Wang MB, Srivatsan ES. Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol Cancer 2011; 10: 12-30.
. Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 1998; 64: 353-356.
. Mona AM, Abo-Zeid, Ayman A, Farghaly. The Anti-mutagenic Activity of Piperine against Mitomycine C induced Sister Chromatid Exchanges and Chromosomal Aberrations in Mice. JGEB 2009; 7: 45-50.
. Selvendiran K, Sakthisekaran D. Chemopreventive effect of piperine on modulating lipid peroxidation and membrane bound enzymes in benzo (α) pyrene induced lung carcinogenesis. Biomed Pharmacother 2004; 58: 264-267.
. Li M, Ciu JR, Ye Y, Min JM, Zhang LH, Wang K, Gares M, Cros J, Wright M, Leung-Tack J. Antitumor activity of Z-ajoene, a natural compound purified from garlic: antimitotic and micro tubule-interaction properties. Carcinogenesis 2002; 23: 573-579.
. de Kok TM, van Breda SG, Manson MM. Mechanisms of combined action of different chemopreventive dietary compounds: a review. Eur J Nutr 2008; 47: 51-59.
. Chrpová D, Kouřimská L, Gordon MH, Veronika Heřmanová, Roubíčková I, Pánek J. Antioxidant Activity of Selected Phenols and Herbs Used in Diets for Medical Conditions. Czech J Food Sci 2010; 28: 317-325.
. Sa G, Das T. Anti cancer effects of curcumin: cycle of life and death. Cell division 2008; 3: 14.
. Kim JW, Gao P, Liu YC, Semenza GL, Dang CV. Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1. Mol cell biol 2007; 27: 7381–7393.
. Doucette CD, Hilchie AL, Liwski R, Hoskin DW. Piperine, a dietary phytochemical, inhibits angiogenesis, J. Nutr Biochem 2013; 24: 231–239.
. Hwang YP, Yun HJ, Kim HG, Han EH, Choi JH, Chung YC, Jeong HG. Suppression of phorbol-12-myristate-13-acetate-induced tumor cell invasion by piperine via the inhibition of PKCα/ERK1/2-dependent matrix metalloproteinase-9 expression. Toxicol Lett 2011; 203: 9–19.
. Somanath PR, Razorenova OV, Chen J, Byzova TV. Akt1 in endothelial cell and angiogenesis. Cell Cycle 2006; 5: 512–518.
. Shukla Y, Kalra N. Cancer chemoprevention with garlic and its constituents. Cancer Lett 2007; 247: 167-181.
. Olusanmi, MJ, Amadi, JE. Studies on the Antimicrobial Properties and Phytochemical Screening of Gallic (Allium sativum) Extract. Ethnobotanical Leaflets 2010; 1: 537 – 545.
. Daugherty M, Polanuyer B, Farrell M, Scholle M, Lykidis A, de Crécy-Lagard V, Osterman A. Complete Reconstitution of the Human Coenzyme A Biosynthetic Pathway via Comparative Genomics. J Biol Sci 2002; 277: 21431–21439.
