Epigallo Catechin Gallate (EGCG) and Sorafenib: A Better Cytoprotective Agent in Diethyl Nitrosamine (DEN) Induced Liver Cancer – An in Vivo Study

  • U Neelamegam Research Scholar, Vinayaka Missions Kirupananda Variyar Medical College and hospital, Vinayaka Mission’s Research Foundation (Deemed to be University), Salem, Tamilnadu, India.
  • V Suganthi Department of Physiology, Vinayaka Missions Kirupananda Variyar Medical College and hospital, Vinayaka Mission’s Research Foundation (Deemed to be University), Salem, Tamilnadu, India.
  • R Muthuvel Department of Biochemistry, Karuna Medical College and Hospital, Palakkad, Kerala, India.
Keywords: Liver Carcinoma, EGCG, Sorafenib, Alpha-fetoprotein

Abstract

Introduction: Carcinoma of the liver is the most frequently noticed malignant neoplasm of the liver and it occupies the third position in cancer-related deaths. Epicatechin-3-gallate, Epigallocatechin-3-gallate, abbreviated as EGCG, constitutes about 50-75% of the catechins. Administration of EGCG inhibits the proliferation of cancerous cells and encourages cell death (apoptosis). Sorafenib is an oral multikinase inhibitor that exerts its inhibitory effects on tumours through angiogenesis inhibition. So, the present study was undertaken to analyse the beneficial effects of naturally occurring agents, EGCG and sorafenib, on carcinoma of the liver.

Materials and Methods: 40 adult male Wistar albino rats were procured and divided into five equal groups. Control animals were in Group 1 and negative controls were in Group 2 Sorafenib treatment was given to Group 3 and EGCG alone was given to Group 4 Group 5 received both sorafenib and EGCG.

Results: We have found that the combined treatment group of EGCG and sorafenib had low levels of AFP, increased levels of mitochondrial enzymes, Phase II enzymes and showed a decrease in enzymes of Phase I and a fall in glycoprotein components level.

Conclusion: Epigallocatechin-gallate (EGCG) when given with sorafenib has shown enhanced cytoprotective effects.

How to cite this article:
Neelamegam U, Suganthi V, Muthuvel R. Epigallo Catechin Gallate (EGCG) and Sorafenib: A Better
Cytoprotective Agent in Diethyl Nitrosamine (DEN) Induced Liver Cancer – An in Vivo Study. Chettinad Health City Med J. 2023;12(2):63-70.

DOI: https://doi.org/10.24321/2278.2044.202329

References

Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, Verslype C, Zagonel V, Fartoux L, Vogel A, Sarker D, Verset G, Chan SL, Knox J, Daniele B, Webber AL, Ebbinghaus SW, Ma J, Siegel AB, Cheng AL, Kudo M; KEYNOTE-224 investigators. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018;19(7):940-52. [PubMed] [Google Scholar]

Yoo C, Kang J, Lim HY, Kim JH, Lee MA, Lee KH, Kim TY, Ryoo BY. Phase I dose-finding study of OPB-111077, a novel STAT3 inhibitor, in patients with advanced hepatocellular carcinoma. Cancer Res Treat. 2019;51(2):510-8. [PubMed] [Google Scholar]

Acharya SK. Epidemiology of hepatocellular carcinoma in India. J Clin Exp Hepatol. 2014 Aug; 4(Suppl 3):S27-33. [PubMed] [Google Scholar]

Paul SB, Sreenivas V, Gulati MS, Madan K, Gupta AK, Mukhopadhyay S, Panda SK, Acharya SK. Incidence of hepatocellular carcinoma among Indian patients with cirrhosis of liver: an experience from a tertiary care center in northern India. Indian J Gastroenterol. 2007;26(6):274-8. [PubMed] [Google Scholar]

Yang CS, Wang X, Lu G, Picinich SC. Cancer prevention by tea: animal studies, molecular mechanisms and human relevance. Nat Rev Cancer. 2009;9(6):429-39. [PubMed] [Google Scholar]

Yang CS, Maliakal P, Meng X. Inhibition of carcinogenesis by tea. Annu Rev Pharmacol Toxicol. 2002;42:25-54. [PubMed] [Google Scholar]

Shimizu M, Weinstein IB. Modulation of signal transduction by tea catechins and related phytochemicals. Mutat Res. 2005;591(1-2):147-60. [PubMed] [Google Scholar]

Khan N, Afaq F, Saleem M, Ahmad N, Mukhtar H. Targeting multiple signaling pathways by green tea polyphenol (-)-epigallocatechin-3- gallate. Cancer Res. 2006;66(5):2500-5. [PubMed] [Google Scholar]

Mandel S, Youdim MB. Catechin polyphenols: neurodegeneration and neuroprotection in neurodegenerative diseases. Free Radic Biol Med. 2004;37(3):304-17. [PubMed] [Google Scholar]

Xiao J, Ho CT, Liong EC, Nanji AA, Leung TM, Lau TY, Fung ML, Tipoe GL. Epigallocatechin gallate attenuates fibrosis, oxidative stress, and inflammation in non-alcoholic fatty liver disease rat model through TGF/SMAD, PI3 K/Akt/FoxO1, and NF-kappa B pathways. Eur J Nutr. 2014;53(1):187-99. [PubMed] [Google Scholar]

El-Mowafy AM, Al-Gayyar MM, Salem HA, El-Mesery ME, Darweish MM. Novel chemotherapeutic and renal protective effects for the green tea (EGCG): role of oxidative stress and inflammatory-cytokine signaling. Phytomedicine. 2010;17(14):1067-75. [PubMed] [Google Scholar]

Morse MA, Sun W, Kim R, He AR, Abada PB, Mynderse M, Finn RS. The role of angiogenesis in hepatocellular carcinoma. Clin Cancer Res. 2019;25(3):912-20. [PubMed] [Google Scholar]

Niebes P. Determination of enzymes and degradation products of glycosaminoglycan metabolism in the serum of healthy and varicose subjects. Clin Chim Acta. 1972;42(2):399-408. [Google Scholar]

Wagner WD. A more sensitive assay discriminating galactosamine and glucosamine in mixtures. Anal Biochem. 1979;94(2):394-6. [PubMed] [Google Scholar]

Warren L. The thiobarbituric acid assay of sialic acids. J Biol Chem. 1959 Aug;234(8):1971-5. [PubMed] [Google Scholar]

Johnson D, Lardy H. [15] Isolation of liver or kidney mitochondria. In: Richard JP, Morgan GR, editors. Methods in enzymology. Vol. 10. Academic Press; 1967. p. 94-6. [Google Scholar]

King J. Isocitrate dehydrogenase. In: King JC, Van D, editors. Practical clinical enzymology. London: Nostrand Co; 1965. p. 363. [Google Scholar]

Mehler AH, Kornberg A, Gbisolia S, Ochoa S. The enzymatic mechanism of oxidation-reductions between malate or isocitrate and pyruvate. J Biol Chem. 1948 Jul;174(3):961-77. [PubMed] [Google Scholar]

T. Omura, R. SatoThe carbon monoxide-binding pigment of liver microsomes: I. Evidence for its hemoprotein nature J. Biol. Chem, 239 (1964), pp. 2370-237

Phillips AH, Langdon RG. Hepatic triphosphopyridine nucleotide-cytochrome c reductase: isolation, characterization, and kinetic studies. J Biol Chem. 1962 Aug;237:2652-60. [PubMed] [Google Scholar]

Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem. 1974 Nov 25;249(22):7130-9. [PubMed] [Google Scholar]

Issalbacher, K.J., M.F. Charbas and R.C. Quinn, 1962. The solublization and partial purification of glucuronyl transferase from rabbit liver microsomes. J. Biol. Chem., 237: 3033-3036.

Hollmann S, Touster O. Alterations in tissue levels of uridine diphosphate glucose dehydrogenase, uridine diphosphate glucuronic acid pyrophosphatase and glucuronyl transferase induced by substances influencing the production of ascorbic acid. Biochim Biophys Acta. 1962;62:338-52. [PubMed] [Google Scholar]

Dodge JT, Mitchell C, Hanahan DJ. The preparation and chemical characteristics of hemoglobin-free ghosts of human erythrocytes. Arch Biochem Biophys. 1963 Jan;100:119-30. [PubMed] [Google Scholar]

Fiske CH, Subbarow Y. The colorimetric determination of phosphorus. J Biol Chem. 1925;66:375. [Google Scholar]

Kuijpers W, Bonting SL, 1970. The cochlear potentials - II. the Nature of the cochlear endolymphatic resting potential. Pflfigers Arch. Eur. J. Physiol. 320, 359–372.

Hjerten S, Pan H. Purification and characterization of two forms of a low-affinity Ca2+-ATPase from erythrocyte membranes. Biochim Biophys Acta. 1983;728:281-8. [PubMed] [Google Scholar]

Ohnishi T, Suzuki T, Suzuki Y, Ozawa K. A comparative study of plasma membrane Mg2+ -ATPase activities in normal, regenerating and malignant cells. Biochim Biophys Acta. 1982 Jan 4;684(1):67-74.

Zhao L, Liu S, Xu J, Li W, Duan G, Wang H, Yang H, Yang Z, Zhou R. A new molecular mechanism underlying the EGCG-mediated autophagic modulation of AFP in HepG2 cells. Cell Death Dis. 2017 Nov;8(11):e3160. [PubMed] [Google Scholar]

Wayner DD, Burton GW, Ingold KU, Barclay LR, Locke SJ. The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping antioxidant activity of human blood plasma. Biochim Biophys Acta. 1987 Jun 22;924(3):408-19. [PubMed] [Google Scholar]

Sohal RS, Weindruch R. Oxidative stress, caloric restriction, and aging. Science. 1996 Jul 5;273(5271):59-63. [PubMed] [Google Scholar]

Kaviarasan S, Ramamurthy N, Gunasekaran P, Varalakshmi E, Anuradha CV. Epigallocatechin-3-gallate(-)protects Chang liver cells against ethanol-induced cytotoxicity and apoptosis. Basic Clin Pharmacol Toxicol. 2007;100(3):151-6. [PubMed] [Google Scholar]

Raza H, John A. In vitro protection of reactive oxygen species-induced degradation of lipids, proteins and 2-deoxyribose by tea catechins. Food Chem Toxicol. 2007 Oct 1;45(10):1814-20. [PubMed] [Google Scholar]

Published
2023-06-30