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http://dx.doi.org/10.7314/APJCP.2015.16.10.4303

Significance of Rumex Vesicarius as Anticancer Remedy Against Hepatocellular Carcinoma: a Proposal-Based on Experimental Animal Studies  

Shahat, Abdelaaty A (Pharmacognosy Department, College of Pharmacy, King Saud University)
Alsaid, Mansour S (Pharmacognosy Department, College of Pharmacy, King Saud University)
Kotob, Soheir E (Hormones Department, National Research Centre)
Ahmed, Hanaa H (Hormones Department, National Research Centre)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.10, 2015 , pp. 4303-4310 More about this Journal
Abstract
Rumex vesicarius is an edible herb distributed in Egypt and Saudi Arabia. The whole plant has significant value in folk medicine and it has been used to alleviate several diseases. Hepatocellular carcinoma (HCC), the major primary malignant tumor of the liver, is one of the most life-threatening human cancers. The goal of the current study was to explore the potent role of Rumex vesicarius extract against HCC induced in rats. Thirty adult male albino rats were divided into 3 groups: (I): Healthy animals received orally 0.9 % normal saline and served as negative control group, (II): HCC group in which rats were orally administered N-nitrosodiethylamine NDEA, (III): HCC group treated orally with R. vesicarius extract in a dose of 400 mg/kg b.wt daily for two months. ALT and AST, ALP and ${\gamma}$-GT activities were estimated. CEA, AFP, AFU, GPC-3, Gp-73 and VEGF levels were quantified. Histopathological examination of liver tissue sections was also carried out. The results of the current study showed that the treatment of the HCC group with R. vesicarius extract reversed the significant increase in liver enzymes activity, CEA, AFP, AFU, glypican 3, golgi 73 and VEGF levels in serum as compared to HCC-untreated counterparts. In addition, the favorable impact of R. vesicarius treatment was evidenced by the marked improvement in the histopathological features of the liver of the treated group. In conclusion, the present experimental setting provided evidence for the significance of R. vesicarius as anticancer candidate with a promising anticancer potential against HCC. The powerful hepatoprotective properties, the potent antiangiogenic activity and the effective antiproliferative capacity are responsible for the anticancer effect of this plant.
Keywords
Hepatocellular carcinoma; polygonaceae; R. vesicarius; angiogenesis; apoptosis; rats;
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1 Chen B, Ning M, Yang G (2012). Effect of Paeonol on antioxidant and immune regulatory activity in hepatocellular carcinoma rats. Molecules, 17, 4672-83.   DOI
2 Chen X (2010). Protective effects of quercetin on liver injury induced by ethanol. Pharmacogn Mag, 6, 135-141.   DOI
3 Coston WM, Loera S, Lau SK, et al (2008). Distinction of hepatocellular carcinoma from benign hepatic mimickers using Glypican-3 and CD34 immunohistochemistry. Am J Surg Pathol, 32, 433-44.   DOI
4 Darwish HA, El-Boghdady NA (2011). Possible involvement of oxidative stress in diethylnitrosamine induced hepatocarcinogenesis, chemopreventive effect of curcumin. J Food Biochem, 37, 353-61.
5 Deuffic-Burban S, Mohamed MK, Larouza B, et al (2006). Expected increase in hepatitis C-related mortality in Egypt due to pre-2000 infections. Hepatol J, 44, 455-61.   DOI
6 Deugnier Y (1984). Serum ${\alpha}$-L-fucosidase, A new marker for the diagnosis of primary hepatic carcinoma. Hepatol, 4, 889-92.   DOI
7 ECCLS (1989). Determination of the catalytic activity concentration in serum on L-aspartate aminotransferase (AST). Clin Chem, 20, 204-11.
8 El-Bakry AA, Mostafa HAM, Alam EA (2012). Antioxidant activity of R. vesicarius at the vegetative stage of growth. Asian J Pharm Clin Res. 5, 111-7.
9 El-Serag HB, Rudolph KL (2007). Hepatocellular carcinoma, epidemiology and molecular carcinogenesis. Gastroenterol, 132, 2557-76.   DOI
10 El-Serag HB (2002). Hepatocellular carcinoma, an epidemiologic view. J Clin Gastroenterol, 35, 72-8.   DOI
11 El-Shahat M, El-Abda S, Alkafafyb M, et al (2012). Potential chemoprevention of diethylnitrosamine-induced hepatocarcinogenesis in rats, Myrrh (Commiphora molmol) vs. turmeric (Curcuma longa). Acta Histochemica, 114, 421-8.   DOI
12 Ezzikouri S, El Feydi AE, Afifi R, et al (2010). Polymorphisms in antioxidant defence genes and susceptibility to hepatocellular carcinoma in a Moroccan population. Free Radic Res, 44, 208-16.   DOI
13 Fang J, Xia C, Cao Z, et al (2005). Apigenin inhibits VEGF and HIF- 1 expression via PI3K/AKT/p70S6K1 and HDM2/p53 pathways. FASEB J, 19, 342-53.   DOI
14 Fang J, Zhou Q, Liu LZ, et al (2007). Apigenin inhibits tumor angiogenesis through decreasing HIF-1alpha and VEGF expression. Carcinogenesis. 28, 858-64.
15 Fentiman IS (2012). Gamma-glutamyl transferase, risk and prognosis of cancer. Br J Cancer, 106, 1467-8.   DOI
16 Fiala S, Fiala ES (1973). Activation by chemical carcinogen of gamma glutamyl transpeptidase in rat and mouse liver. J Natl Cancer Inst, 51, 151-8.   DOI
17 Fontanini G, Vignati S, Boldrini L, et al (1997). Vascular endothelial growth factor is associated with neovascularization and influences progression of non-small cell lung carcinoma. Clin Cancer Res, 3, 861-5.
18 Fu B, Xue J, Li Z, et al (2007). Chrysin inhibits expression of hypoxiainducible factor-1alpha through reducing hypoxiainducible factor-1alpha stability and inhibiting its protein synthesis. Mol Cancer Ther, 6, 220-226.   DOI
19 Gao J, Xie L, Yang WS (2012). Risk factors of hepatocellular carcinoma current status and perspectives. Asian Pac J Cancer Prev, 13, 743-52.   DOI   ScienceOn
20 Green RM, Flamm S (2002). AGA technical review on the evaluation of liver chemistry tests. Gastroenterol, 123, 1367-84.   DOI
21 Hirai H (1982). Alpha fetoprotein. In , Chu T M, ed. Biochemical Markers for Cancer. New York, marcel dekker, 23-59.
22 Holmes EH, Hakomori SI (1982). Isolation and characterization of a new fucoganglioside accumulated in precancerous rat liver and in rat hepatoma induced by N-2- acetylaminofluorene. J Biol Chem, 257, 7698-703.
23 Hosny G, Farahat N, Tayel H, Hainaut P (2008). Ser-249 TP53 and CTNNB1 mutations in circulating free DNA of Egyptian patients with hepatocellular carcinoma versus chronic liver diseases. Cancer Lett, 264, 201-8.   DOI
24 Imran M, Raja MM, Basith JA (2011). Determination of total phenol, flavonoid and antioxidant activity of edible mushrooms pleurotus florida and pleurotus eous. Int Food Res J, 18, 574-7.
25 Janbaz K, Saeed S, Gilani A (2004). Studies on the protective effects of caffeic acid and quercetin on chemical-induced hepatotoxicity in rodents. Phytomedicine, 11, 424-30.   DOI
26 Jozkowicz A, Cooke JP, Guevara I, et al (2001). Genetic augmentation of nitric oxide synthase increases the vascular generation of VEGF. Cardiovasc Res, 51, 773-83.   DOI
27 Khan TH. (2012). Soy diet diminish oxidative injure and early promotional events induced by CCl4 in rat liver. Int J Pharmacol, 8, 30-8.   DOI
28 Kim JM, Kwon CHD, Joh JW, et al (2013). The effect of alkaline phosphatase and intrahepatic metastases in large hepatocellular carcinoma. World J Surg Oncol, 11, 40.   DOI
29 Ladd, J, Lu H, Taylor AD (2009). Direct detection of carcinoembryonic antigen autoantibodies in clinical human serum samples using a surface plasmon resonance sensor. Colloids Surf B Biointerfaces, 70, 1-6.   DOI
30 Koss B, Greengurd O (1982). Effect of neoplasma on the content and activity of alkaline phosphatase and gamma glutamyl transpeptidase in uninvolved host tissues. Cancer Res, 42, 2146-51.
31 Lakshmi CP, Chakradhar RPS, Rao JL, et al (2009). EPR and IR spectral investigations on some leafy vegetables of Indian origin. Spectrochimica Acta Part A, 74, 140-7.   DOI
32 Lazarevich NL (2000). Review, molecular mechanisms of alphafetoprotein gene expression. Biochemistry, 65, 117-33.
33 Li CJ, Wang C, Padee AB (1995). Induction of apoptosis by beta-lapachone in human prostate cancer cells. Cancer Res, 55, 3712-5.
34 Li N, Xiao B, Chen XB (2008). Relationship between expression of CEA, E-cadherin and liver metastasis in colorectal cancer. Chin J Clin Oncol, 5, 429-32.   DOI
35 Liao DJ, Blanck A, Eneroth P, et al (2001). Diethylnitrosamine causes pituitary damage, disturbs hormone levels, and reduces sexual dimorphism of certain liver functions in the rat. Environ Health Perspect, 109, 943-7.   DOI
36 Liu JG, Zhao HJ, Liu YJ, Et al (2012). Effect of two selenium sources on hepatocarcinogenesis and several angiogenic cytokines in diethylnitrosamine-induced hepatocarcinoma rats. J Trace Elem Med Biol, 26, 255-61.   DOI
37 Lyer P, Zekri AR, Hung CW, et al (2010). Concordance of DNA methylation pattern in plasma and tumor DNA of Egyptian hepatocellular carcinoma patients. Exp Mol Pathol, 88, 107-11.   DOI
38 Matkowski A (2008). Plant in vitro culture for the production of antioxidants-a review. Biotechnol Adv, 26, 548-60.   DOI
39 Malaguarnera G, Giordano M, Paladina I, et al (2010). Serum markers of hepatocellular carcinoma. Dig Dis Sci, 55, 2744-55   DOI
40 Masuku SKS, Owaga EE, Gadaga TH, et al (2014). Molecular mechanism of the effects of quercetin on human breast cancer cells. Direct Res J Health Pharmacol, 2, 6-9.
41 Mirzoeva S, Kim ND, Chiu K, et al (2008). Inhibition of HIF-1 alpha and VEGF expression by the chemopreventive bioflavonoid apigenin is accompanied by Akt inhibition in human prostate carcinoma PC3-M cells. Mol Carcinog, 47, 686-700.   DOI
42 Mitupatum T, Aree K, Kittisenachai S, et al (2015). Hep88 mAb-mediated paraptosis-like apoptosis in HepG2 cells via downstream upregulation and activation of caspase-3, caspase-8 and caspase-9. Asian Pac J Cancer Prev, 16, 1771-9   DOI
43 Moon YJ, Shin BS, An G, et al (2008). Biochanin A inhibits breast cancer tumor growth in a murine xenograft model. Pharm Res. 25, 2158-63.   DOI
44 Motalleb G, Hanachi P, Fauziah O, et al (2008). Effect of Berberis vulgaris fruit extract on alpha-fetoprote in gene expression and chemical carcinogen metabolizing enzymes activities in hepatocarcinogenesis rats. Iran J Cancer Prev, 1, 33-44.
45 Mukhtar H, Das M, Khan WA, et al (1988). Exceptional activity of tannic acid among naturally occurring plant phenols in protecting against 7,12-dimethylbenz(a)anthracene-, benzo(a)- pyrene-, 3-methylcholanthrene-, and N-methyl- N-nitrosourea-induced skin tumorigenesis in mice. Cancer Res. 48, 2361-5.
46 Powis G, Kirkpatrick L (2004). Hypoxia inducible factor-1alpha as a cancer drug target. Mol Cancer Ther, 3, 647-54.
47 Saleem M, Ahmed B, Karim M, et al (2014). Hepatoprotective effect of aqeous methanolic extract of Rumex dentatus in paracetamol-induced hepatotoxicity in mice. Bangladesh J Pharmacol, 9, 284-9
48 Raghavendra M, and Reddy AKG (2011). Acute and chronic toxicity studies of ethanolic extract of Rumex vesciscarius L. in experimental animals. J Sci, 1, 16-20
49 Ramos S (2008). Cancer chemoprevention and chemotherapy, dietary polyphenols and signalling pathways. Mol Nutr Food Res. 52, 507-52.   DOI
50 Rashed KN, Chang CW, Wu LY, et al (2013). Hepatoprotective activity of Diospyros lotus fruits on acute liver injury induced by carbon tetrachloride and phytochemical analysis. Topcls J Herb Med, 2, 75-83.
51 Schwartz MK (1987). Tumor markers in diagnosis and screening. In, Ting SW, Chen JS, Schwartz MK, eds. human tumor markers, amsterdam, elsevier science, 3-16.
52 Sell S, Becker F, Leffert HL, et al (1983). ${\alpha}$ -Fetoprotein as a marker for early events and carcinoma development during chemical hepatocarcinogenesis. Environ Sci Res, 29, 271-93.
53 Seufi A, Safinz S, Ibrahim S, et al (2009). Preventive effect of the flavonoid, quercetin, on hepatic cancer in rats via oxidant/ antioxidant activity, molecular and histological evidences. J Exp Clin Canc Res, 28, 80-6.   DOI
54 Shahat AA, Alsaid MS, Alyahya MA, et al (2013). NAD(P)H, quinoneoxidoreductase 1 (NQO1) Inducer activity of some saudi arabian medicinal plants. Planta Medica, 79, 459-64   DOI
55 Song EK, Kim JH, Kim JS, et al (2003). Hepatoprotective phenolic constituents of Rhodiola sachalinensis on tacrineinduced cytotoxicity in Hep G2 cells. Phytother Res, 17, 563-65.   DOI
56 Tong MJ, Chavalitdhamrong D, Lu DSK, et al (2010). Survival in Asian Americans after treatments for hepatocellular carcinoma, a seven-year experience at UCLA. J Clin Gastroenterol, 44, 63-70.   DOI
57 Song Y, Jin S, Cui L, et al (2013). Immunomodulatory effect of Stichopus japonicus acid mucopolysaccharide on experimental hepatocellular carcinoma in rats. Molecules, 18, 7179-93.   DOI
58 Thomas MB, Jaffe D, Chotietal MM (2010). Hepatocellular carcinoma, consensus recommendations of the National Cancer Institute Clinical Trials Planning Meeting. Clinical Oncol, 28, 3994-4005.   DOI
59 Tietz NW (1995). Clinical guide to laboratory Tests, 3rd ed AACC.
60 Vanisree AJ , Shyamaladevi CS (1998). Effect of therapeutic strategy established by N-acetyl cystine and vitamin C on the activities of tumour marker enzymes in vitro. Ind J Pharmacol, 31, 275-8.
61 Vischer P, Reutter W (1978). Specific alterations of fucoprotein biosynthesis in the plasma membrane of Morris hepatoma 7777. Eur J Biochem, 84, 363-8.   DOI
62 Willyard C (2007). Researchers look for 'sweet' method to diagnose cancer. Nat Med, 13, 1267   DOI
63 Yang R-Z, Park S, Reagan WJ, et al (2009). Alanine aminotransferase isoenzymes, molecular cloning and quantitative analysis of tissue expression in rats and serum elevation in liver toxicity. Hepatol, 49, 598-607.   DOI
64 Zeng YW, Du J, Pu XY, et al (2015). Coevolution between human’s anticancer activities and functional foods from crop origin center in the world. Asian Pac J Cancer Prev, 16, 2119-28   DOI
65 Ahmed MM, Aleisa AM, Al-Rejaie SS, et al (2010). Thymoquinone attenuates diethylnitrosamine induction of hepatic carcinogenesis through antioxidant signaling. Oxid Med Cell Longev, 3, 254-261.   DOI
66 Zhang H, Guo Z, Wu N, et al (2012). Two novel naphthalene glucosides and an anthraquinone isolated from rumex dentatus and their antiproliferation activities in four cell lines. Molecules, 17, 843-50.   DOI
67 Aalinkeel R, Bindukumar B, Reynolds JL (2008). The dietary bioflavonoid, quercetin, selectively induces apoptosis of prostate cancer cells by down-regulating the expression of heat shock protein 90. Prostate, 68, 1773-89.   DOI
68 Abdallah IZ, Khattab HA (2004). Protective role of lycopene against diethylnitrosamine induced experimental hepatocarcinogenesis. Egypt J Hosp Med, 16, 1-13.
69 Abou Elfotoh A, Shams A, Anthony P, et al (2013). Lipophilic constituents of Rumex vesicarius L. and Rumex dentatus L. Antioxidants, 2, 167-80.   DOI
70 Ahmed HH, Shousha WG, El-Mezayen HA, et al (2013). In vivo antitumor potential of carvacerol against hepatocellular carcinoma in rat moderl. World J Pharm Pharmaceut Sci, 2, 2367-96.
71 Anso E, Zuazo A, Irigoyen M, et al (2010). Flavonoids inhibit hypoxia-induced vascular endothelial growth factor expression by a HIF-1 independent mechanism. Biochem Pharmacol, 79, 1600-9   DOI
72 Armitage P, Berry G (1987). Comparison of several groups. in, statistical method in medical research. 2nd ed., Oxford; blockwell significant publication, pp.186-213.
73 Barbosa-Filho JM, Alencar AA, de Andrade Tomaz AC, et al (2008). Sources of alpha-, beta-, gamma-, delta- and epsiloncarotenes, a twentieth century review. Brazil J Pharma, 18, 135-54.   DOI
74 Bagli E, Stefaniotou M, Morbidelli L, et al (2004). Luteolin inhibits vascular endothelial growth factor-induced angiogenesis; inhibition of endothelial cell survival and proliferation by targeting phosphatidylinositol 30-kinase activity. Cancer Res, 64, 7936-46.   DOI
75 Balamurugan K (2011). Molecular investigation on the efficacy of luteolin as a potent therapeutic agent for experimentally induced hepatocellular carcinoma in wistar albino rats. PhD. thesis, university of prist, vallam, thanjavur - 613 403.
76 Banchroft JD, Stevens A, Turner DR (1996). Theory and Practice of histological techniques.4th ed., New York, London, San Francisco, Tokyo; churchill livingstone.
77 Bishayee A. (2012). Recent advances in the prevention and therapy of hepatocellular carcinoma. Current Cancer Drug Targets, 12, 1043-4.
78 Buchler P, Reber HA, Buchler MW, et al (2004). Antiangiogenic activity of genistein in pancreatic carcinoma cells is mediated by the inhibition of hypoxia-inducible factor-1 and the downregulation of VEGF gene expression. Cancer, 100, 201-10.   DOI
79 Center MM, Jemal A (2011). International trends in liver cancer incidence rates. Cancer Epidemiol Biomarkers Prev, 20, 2362-8.   DOI
80 Chakraborty T, Chatterjee A, Rana A, et al (2007). Carcinogeninduced early molecular events and its implication in the initiation of chemical hepatocarcinogenesis in rats, chemopreventive role of vanadium on this process. Biochim Biophys Acta, 1772, 48-59.   DOI