Antineoplastic Activities of Grape Seed Proanthocyanidin Extract against Ehrlich Solid Tumor Bearing Mice Induced Alterations in AFP, CEA, TNF-α and DNA Damage
Asian Oncology Research Journal,
Page 1-12
Abstract
Background and Objective: Cancer is initiated due to abnormalities in the DNA of the affected cells leading to an extra mass of tissue termed a tumor. Breast cancer is the most public cancer amongst women world-wide. The present work is designed to investigate the ameliorating potential effects of grape seed proanthocyanidin extract (GSPE) in inhibition of Ehrlich cells growth and tumor development as a model for breast cancer. Also; the present work is designed to investigate the effect of GSPE on the changes in the levels of AFP, CEA, TNF-α and hematological alterations, and DNA damage examination on Ehrilch solid tumor (EST) bearing mice.
Materials and Methods: A total of 40 female mice were evenly distributed amongst four groups (G1, control group; G2, GSPE group; G3, EST group; IV, EST+GSPE group).
Results: Results revealed increased incidences of tumor growth in the untreated EST group, along with elevated levels of serum AFP, CEA, TNF-α, WBCs, platelets and DNA damage and an associated reduction in RBCs and Hb%. Treatment of EST with GSPE (EST+GSPE) modulates and improved these changes in CBC, tumor markers and DNA damage as compared to mice bearing EST.
Conclusion: This finding calls for more investigation on the benefits of grape seed proanthocyanidin extract (GSPE) as antineoplastic activity on other tumors as Ehrlich ascites carcinoma or cancer.
Keywords:
- Ehrlich solid tumour
- GSPE
- AFP
- CEA
- TNF-α
- DNA damage
- mouse.
How to Cite
Ahmed, M., Ehab, T., Eldin Ahmed, S. N., M. Mona, E., & M. Haneen, H. (2018). Antineoplastic Activities of Grape Seed Proanthocyanidin Extract against Ehrlich Solid Tumor Bearing Mice Induced Alterations in AFP, CEA, TNF-α and DNA Damage. Asian Oncology Research Journal, 2(1), 1-12. Retrieved from https://journalaorj.com/index.php/AORJ/article/view/30091
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Aldubayan MA, Elgharabawy RM, Ahmed AS, Tousson E. Antineoplastic activity and curative role of avenanthramides against the growth of ehrlich solid tumors in mice. Oxidative Medicine and Cellular Longevity. 2019;12:5162687. DOI:10.1155/2019/5162687
Eldaim MA, Tousson E, El Sayed IE, El AE, Elsharkawy HN. Grape seeds proanthocyanidin extract ameliorates Ehrlich solid tumor induced renal tissue and DNA damage in mice. Biomedicine & Pharmacotherapy. 2019;115:108908.
Saggu S, Sakeran MI, Zidan N, Tousson E, Mohan A, Rehman H. Ameliorating effect of chicory (Chichorium intybus L.) fruit extract against 4-tert-octylphenol induced liver injury and oxidative stress in male rats. Food and Chemical Toxicology. 2014;72:138-146.
Salama AF, Abdel-Hamid NM, El-Sheekh M, Tosson E, Gabr AM. Spirulina platensis microalgae protects against diethyl nitrosamine carcinogenic effect on female albino rats. Alexandria Journal of Veterinary Sciences. 2017;53(1):167-79.
Salama AF, Tousson EM, Ibrahim WM, Elwan MS. Ameliorating role of folic acid in eltroxine induced hyperthyroid and oxidative stress in rat cortex, hypothalamus and hippocampus. Alexandria Journal of Veterinary Sciences. 2017;55(1):210-6.
Oyouni AA, Saggu S, Tousson E, Rehman H. Immunosuppressant drug tacrolimus induced mitochondrial nephrotoxicity, modified PCNA and Bcl-2 expression attenuated by Ocimum basilicum L. in CD1 mice. Toxicology Reports. 2018;5: 687-94.
Tousson E, Hafez E, Masoud A, Hassan AA. Abrogation by curcumin on testicular toxicity induced by cisplatin in rats. J Cancer Res Treat. 2014;2(3):64-8.
Tousson E, Hegazy M, Hafez E, Ahmed EA. The effect of L-carnitine on amethopterin-induced toxicity in rat large intestine. J Cancer Res Treat. 2014;2(3): 55-63.
Tousson E, Atteya Z, El-Atrash E, Jeweely OI. Abrogation by ginkgo byloba leaf extract on hepatic and renal toxicity induced by methotrexate in rats. J Cancer Res Treat. 2014;2(3):44-51.
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Tousson E, Hafez E, Zaki S, Gad A. P53, Bcl-2 and CD68 expression in response to amethopterin-induced lung injury and ameliorating role of l-carnitine. Biomedicine & Pharmacotherapy. 2014;68(5):631-9.
Bayomy MF, Tousson E, Ahmed AA. Protective role of rosemary against anticancer drug etoposide-induced testicular toxicity and oxidative stress in rats. Journal of Advanced Trends in Basic and Applied Science. 2017;1(2):1-5.
El-Keey MM, El Ghonamy MA, Ali TM, Ibrahim WM, Tousson E. Effect of sulforaphane and methotrexate combined treatment on histone deacetylase activity in solid ehrlich carcinoma. Journal of Bioscience and Applied Research. 2017;3 (3):62-69.
Moustafa AH, Ali EM, Moselhey SS, Tousson E, El-Said KS. Effect of coriander on thioacetamide-induced hepatotoxicity in rats. Toxicology and Industrial Health. 2014;30(7):621-9.
Salama AF, Tousson E, Shalaby KA, Hussien HT. Protective effect of curcumin on chloroform as by-product of water chlorination induced cardiotoxicity. Biomedicine & Preventive Nutrition. 2014;4 (2):225-30.
Basuony M, Hafez E, Tousson E, Massoud A, Elsomkhraty S, Eldakamawy S. Beneficial role of panax ginseng root aqueous extract against cisplatin induced blood toxicity in rats. Am J Biol Chem. 2015;3(1):1-7.
El-Demerdash FM, Tousson EM, Kurzepa J, Habib SL. Xenobiotics, oxidative stress, and antioxidants. Oxidative medicine and cellular longevity; 2018.
DOI:10.1155/2018/9758951
Tousson E, Keshta AT, Hussein Y, Fekry RM, Abo-Ghaneima WK. Renal protective effect of ginkgo biloba and l-carnitine extracts against pentylenetetrazol induced toxicity, oxidative stress, injury and proliferation alternation in epileptic rats. Annual Research & Review in Biology. 2019;1-3.
El-Masry TA, Al-Shaalan NH, Tousson E, El-Morshedy K, Al-Ghadeer A. P53 expression in response to equigan induced testicular injury and oxidative stress in male rat and the possible prophylactic effect of star anise extracts. Annual Research & Review in Biology. 2017;14 (1):1-8. Available:https://doi.org/10.9734/ARRB/2017/34318
Elmasry TA, Al-Shaalan NH, Tousson E, El-Morshedy K, Al-Ghadeer A. Star anise extracts modulation of reproductive parameters, fertility potential and DNA fragmentation induced by growth promoter Equigan in rat testes. Brazilian Journal of Pharmaceutical Sciences. 2018;54(1).
Abd Eldaim MA, Tousson E, El Sayed IE, Awd WM. Ameliorative effects of Saussurea lappa root aqueous extract against Ethephon‐induced reproductive toxicity in male rats. Environmental toxicology. 2019;34(2):150-9.
Akela MA, El Atrash AM, El Kilany MI, Tousson E. Qualitative and quantitative characterization of biologically active compounds of rosemary (Rosmarinus officinalis) leaf extract. Journal of Advanced Trends in Basic and Applied Science. 2018;2(1):59-64.
Oyouni AA, Saggu S, Tousson E, Mohan A, Farasani A. Mitochondrial nephrotoxicity induced by tacrolimus (FK-506) and modulatory effects of Bacopa monnieri (Farafakh) of Tabuk Region. Pharmacognosy Research. 2019;11(1):20.
Tousson E, Elgharabawy RM, Elmasry TA. Grape seed proanthocyanidin ameliorates cardiac toxicity induced by boldenone undecylenate through inhibition of NADPH oxidase and reduction in the expression of NOX2 and NOX4. Oxidative medicine and cellular longevity. 2018;12.
Article ID 9434385.
Available:https://doi.org/10.1155/2018/9434385
Tousson E, Bayomy MF, Ahmed AA. Rosemary extract modulates fertility potential, DNA fragmentation, injury, KI67 and P53 alterations induced by etoposide in rat testes. Biomedicine & Pharmacotherapy. 2018;98:769-74.
Tousson E, Hafez E, Zaki S, Gad A. The cardioprotective effects of L-carnitine on rat cardiac injury, apoptosis and oxidative stress caused by amethopterin. Environmental Science and Pollution Research. 2016;23(20):20600-8.
Bolkiny Y, Tousson E, El-Atrsh A, Akela M, Farg E. Costus root extract alleviates blood biochemical derangements of experimentally-induced hypo and hyperthyroidism in mice. Annual Research & Review in Biology. 2019;31(5):1-0.
Bagchi D, Swaroop A, Preuss HG, et al. Free radical scav¬enging, antioxidant and cancer chemoprevention by grape seed proanthocyanidin: An overview. Mutat Res. 2014;768:69-73.
Li SG, Ding YS, Niu Q, Xu SZ, Pang LJ, Ma RL, Jing MX, Feng GL, Liu JM, Guo SX. Grape seed proanthocyanidin extract alleviates arsenic-induced oxidative reproductive toxicity in male mice. Biomed. Environ Sci. 2015;28:272–280.
Al-Rasheed NM, El-Masry TA, Tousson E, Hassan HM, Al-Ghadeer A. Hepatic protective effect of grape seed proanthocyanidin extract against Gleevec-induced apoptosis, liver Injury and Ki67 alterations in rats. Brazilian Journal of Pharmaceutical Sciences. 2018;54(2). e17391
El-Atrash A, Zaki S, Tousson E, Shoir MA. Protective potential of grape seed extract against monosodium glutamate induced liver toxicity and oxidative stress in young rats. Journal of Advanced Trends in Basic and Applied Science. 2017;1(3):257-262.
Al-Rasheed NM, El-Masry TA, Tousson E, Hassan HM, Al-Ghadeer A. Protective potential of grape seed proanthocyandins extract against glivec (Imatinib Mesylate) induced liver toxicity and oxidative stress in male rats. Annual Research & Review in Biology. 2017;20(6):1-9.
Tousson E, Rafat BM, Hessien M, El Barbary AA, Sami A. P53 and Bcl2 apoptosis proteins in meso-2, 3-dimercaptosuccinic acid treated lead-intoxicated rabbits. Toxicology and Industrial Health. 2011;27(3):271-8.
El-Moghazy M, Zedan NS, El-Atrsh AM, El-Gogary M, Tousson E. The possible effect of diets containing fish oil (omega-3) on hematological, biochemical and histopathogical alterations of rabbit liver and kidney. Biomedicine & Preventive Nutrition. 2014;4(3):371-7.
El Atrash A, Tousson E, Gad A, Allam S. Hematological and biochemical changes caused by antidepressants amitriptyline induced cardiac toxicity in male rats. Asian Journal of Cardiology Research. 2019;23: 1-6.
Kabel AM, Abdel-Rahman MN, El-Sisi A, Haleem, MS, Ezzat NM, El Rashidy MA. Effect of atorvastatin and methotrexate on solid ehrlich tumor. Eur J Pharmacol. 2013; 713(13):47-53.
Mutar TF, Gazia MA, Salem SB, Hammed EH, Tousson E. Ehrlich ascites carcinoma bearing mice as model of human hepatocellular carcinoma. Asian Journal of Research and Reports in Hepatology. 2019;18:1-9.
Zhu FM, Du B, Li J. Effect of ultrafine grinding on physicochemical and antioxidant properties of dietary fiber from wine grape pomace. Food Sci Technol Int. 2014;20:55–62.
Zhen J, Qu Z, Fang H, Fu L, Wu Y, Wang H, Zang H, Wang W. Effects of grape seed proanthocyanidin extract on pentylenetetrazole-induced kindling and associated cognitive impairment in rats. Int J Mol Med. 2014;34:391–398.
Zhou K, Raffoul JJ. Potential anticancer properties of grape antioxidants. J Oncol, 2015;803294.
Dinicola S, Pasqualato A, Cucina A, et al. Grape seed extract suppresses MDA-MB231 breast cancer cell migration and invasion. European Journal of Nutrition. 2014;53(2):421–431.
DOI: 10.1007/s00394-013-0542-6
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Guo F, Hu Y, Niu Q, Li Y, Ding Y, Ma R, Wang X, Li S, Xie J. Grape seed proanthocyanidin extract inhibits human esophageal squamous cancerous cell line eca109 via the nf-κb signaling pathway. Mediators of Inflammation; 2018.
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Choi WT, Kakar S. Immunohistochemistry in the diagnosis of hepatocellular carcinoma. Gastroenterology Clinics. 2017; 46(2):311-25.
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Del Bas JM, Fernández-Larrea J, Blay M, Ardèvol A, Salvadó MJ, Arola L, Bladé C. Grape seed procyanidins improve atherosclerotic risk index and induce liver CYP7A1 and SHP expression in healthy rats. The FASEB Journal. 2005;19(3):479-81.
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DeSantis C, Ma J, Bryan L, Jemal A. Breast cancer statistics. CA: A Cancer Journal for Clinicians. 2013;64(1):52-62.
Wang X, Mo F, Bo H, Xiao L, Chen G, Zeng P, et al. Upregulated expression of long non-coding rna, linc00460, suppresses proliferation of colorectal cancer. J. Cancer. 2018;9(16):2834-2843. DOI:10.7150/jca.26046
Aldubayan MA, Elgharabawy RM, Ahmed AS, Tousson E. Antineoplastic activity and curative role of avenanthramides against the growth of ehrlich solid tumors in mice. Oxidative Medicine and Cellular Longevity. 2019;12:5162687. DOI:10.1155/2019/5162687
Eldaim MA, Tousson E, El Sayed IE, El AE, Elsharkawy HN. Grape seeds proanthocyanidin extract ameliorates Ehrlich solid tumor induced renal tissue and DNA damage in mice. Biomedicine & Pharmacotherapy. 2019;115:108908.
Saggu S, Sakeran MI, Zidan N, Tousson E, Mohan A, Rehman H. Ameliorating effect of chicory (Chichorium intybus L.) fruit extract against 4-tert-octylphenol induced liver injury and oxidative stress in male rats. Food and Chemical Toxicology. 2014;72:138-146.
Salama AF, Abdel-Hamid NM, El-Sheekh M, Tosson E, Gabr AM. Spirulina platensis microalgae protects against diethyl nitrosamine carcinogenic effect on female albino rats. Alexandria Journal of Veterinary Sciences. 2017;53(1):167-79.
Salama AF, Tousson EM, Ibrahim WM, Elwan MS. Ameliorating role of folic acid in eltroxine induced hyperthyroid and oxidative stress in rat cortex, hypothalamus and hippocampus. Alexandria Journal of Veterinary Sciences. 2017;55(1):210-6.
Oyouni AA, Saggu S, Tousson E, Rehman H. Immunosuppressant drug tacrolimus induced mitochondrial nephrotoxicity, modified PCNA and Bcl-2 expression attenuated by Ocimum basilicum L. in CD1 mice. Toxicology Reports. 2018;5: 687-94.
Tousson E, Hafez E, Masoud A, Hassan AA. Abrogation by curcumin on testicular toxicity induced by cisplatin in rats. J Cancer Res Treat. 2014;2(3):64-8.
Tousson E, Hegazy M, Hafez E, Ahmed EA. The effect of L-carnitine on amethopterin-induced toxicity in rat large intestine. J Cancer Res Treat. 2014;2(3): 55-63.
Tousson E, Atteya Z, El-Atrash E, Jeweely OI. Abrogation by ginkgo byloba leaf extract on hepatic and renal toxicity induced by methotrexate in rats. J Cancer Res Treat. 2014;2(3):44-51.
Tousson E, Hafez E, Zaki S, Gad A. P53, Bcl-2 and CD68 expression in response to amethopterin-13 Bagchi D, Garg A, Krohn RL, Bagchi M, Tran MX, Stohs SJ: Oxygen free radical scavenging abilities of vitamins C and E and a grape seed proanthocyanidin extract in vitro. Res Commun Mol Pathol Pharmacol. 1997;95: 179–189.
Tousson E, Hafez E, Zaki S, Gad A. P53, Bcl-2 and CD68 expression in response to amethopterin-induced lung injury and ameliorating role of l-carnitine. Biomedicine & Pharmacotherapy. 2014;68(5):631-9.
Bayomy MF, Tousson E, Ahmed AA. Protective role of rosemary against anticancer drug etoposide-induced testicular toxicity and oxidative stress in rats. Journal of Advanced Trends in Basic and Applied Science. 2017;1(2):1-5.
El-Keey MM, El Ghonamy MA, Ali TM, Ibrahim WM, Tousson E. Effect of sulforaphane and methotrexate combined treatment on histone deacetylase activity in solid ehrlich carcinoma. Journal of Bioscience and Applied Research. 2017;3 (3):62-69.
Moustafa AH, Ali EM, Moselhey SS, Tousson E, El-Said KS. Effect of coriander on thioacetamide-induced hepatotoxicity in rats. Toxicology and Industrial Health. 2014;30(7):621-9.
Salama AF, Tousson E, Shalaby KA, Hussien HT. Protective effect of curcumin on chloroform as by-product of water chlorination induced cardiotoxicity. Biomedicine & Preventive Nutrition. 2014;4 (2):225-30.
Basuony M, Hafez E, Tousson E, Massoud A, Elsomkhraty S, Eldakamawy S. Beneficial role of panax ginseng root aqueous extract against cisplatin induced blood toxicity in rats. Am J Biol Chem. 2015;3(1):1-7.
El-Demerdash FM, Tousson EM, Kurzepa J, Habib SL. Xenobiotics, oxidative stress, and antioxidants. Oxidative medicine and cellular longevity; 2018.
DOI:10.1155/2018/9758951
Tousson E, Keshta AT, Hussein Y, Fekry RM, Abo-Ghaneima WK. Renal protective effect of ginkgo biloba and l-carnitine extracts against pentylenetetrazol induced toxicity, oxidative stress, injury and proliferation alternation in epileptic rats. Annual Research & Review in Biology. 2019;1-3.
El-Masry TA, Al-Shaalan NH, Tousson E, El-Morshedy K, Al-Ghadeer A. P53 expression in response to equigan induced testicular injury and oxidative stress in male rat and the possible prophylactic effect of star anise extracts. Annual Research & Review in Biology. 2017;14 (1):1-8. Available:https://doi.org/10.9734/ARRB/2017/34318
Elmasry TA, Al-Shaalan NH, Tousson E, El-Morshedy K, Al-Ghadeer A. Star anise extracts modulation of reproductive parameters, fertility potential and DNA fragmentation induced by growth promoter Equigan in rat testes. Brazilian Journal of Pharmaceutical Sciences. 2018;54(1).
Abd Eldaim MA, Tousson E, El Sayed IE, Awd WM. Ameliorative effects of Saussurea lappa root aqueous extract against Ethephon‐induced reproductive toxicity in male rats. Environmental toxicology. 2019;34(2):150-9.
Akela MA, El Atrash AM, El Kilany MI, Tousson E. Qualitative and quantitative characterization of biologically active compounds of rosemary (Rosmarinus officinalis) leaf extract. Journal of Advanced Trends in Basic and Applied Science. 2018;2(1):59-64.
Oyouni AA, Saggu S, Tousson E, Mohan A, Farasani A. Mitochondrial nephrotoxicity induced by tacrolimus (FK-506) and modulatory effects of Bacopa monnieri (Farafakh) of Tabuk Region. Pharmacognosy Research. 2019;11(1):20.
Tousson E, Elgharabawy RM, Elmasry TA. Grape seed proanthocyanidin ameliorates cardiac toxicity induced by boldenone undecylenate through inhibition of NADPH oxidase and reduction in the expression of NOX2 and NOX4. Oxidative medicine and cellular longevity. 2018;12.
Article ID 9434385.
Available:https://doi.org/10.1155/2018/9434385
Tousson E, Bayomy MF, Ahmed AA. Rosemary extract modulates fertility potential, DNA fragmentation, injury, KI67 and P53 alterations induced by etoposide in rat testes. Biomedicine & Pharmacotherapy. 2018;98:769-74.
Tousson E, Hafez E, Zaki S, Gad A. The cardioprotective effects of L-carnitine on rat cardiac injury, apoptosis and oxidative stress caused by amethopterin. Environmental Science and Pollution Research. 2016;23(20):20600-8.
Bolkiny Y, Tousson E, El-Atrsh A, Akela M, Farg E. Costus root extract alleviates blood biochemical derangements of experimentally-induced hypo and hyperthyroidism in mice. Annual Research & Review in Biology. 2019;31(5):1-0.
Bagchi D, Swaroop A, Preuss HG, et al. Free radical scav¬enging, antioxidant and cancer chemoprevention by grape seed proanthocyanidin: An overview. Mutat Res. 2014;768:69-73.
Li SG, Ding YS, Niu Q, Xu SZ, Pang LJ, Ma RL, Jing MX, Feng GL, Liu JM, Guo SX. Grape seed proanthocyanidin extract alleviates arsenic-induced oxidative reproductive toxicity in male mice. Biomed. Environ Sci. 2015;28:272–280.
Al-Rasheed NM, El-Masry TA, Tousson E, Hassan HM, Al-Ghadeer A. Hepatic protective effect of grape seed proanthocyanidin extract against Gleevec-induced apoptosis, liver Injury and Ki67 alterations in rats. Brazilian Journal of Pharmaceutical Sciences. 2018;54(2). e17391
El-Atrash A, Zaki S, Tousson E, Shoir MA. Protective potential of grape seed extract against monosodium glutamate induced liver toxicity and oxidative stress in young rats. Journal of Advanced Trends in Basic and Applied Science. 2017;1(3):257-262.
Al-Rasheed NM, El-Masry TA, Tousson E, Hassan HM, Al-Ghadeer A. Protective potential of grape seed proanthocyandins extract against glivec (Imatinib Mesylate) induced liver toxicity and oxidative stress in male rats. Annual Research & Review in Biology. 2017;20(6):1-9.
Tousson E, Rafat BM, Hessien M, El Barbary AA, Sami A. P53 and Bcl2 apoptosis proteins in meso-2, 3-dimercaptosuccinic acid treated lead-intoxicated rabbits. Toxicology and Industrial Health. 2011;27(3):271-8.
El-Moghazy M, Zedan NS, El-Atrsh AM, El-Gogary M, Tousson E. The possible effect of diets containing fish oil (omega-3) on hematological, biochemical and histopathogical alterations of rabbit liver and kidney. Biomedicine & Preventive Nutrition. 2014;4(3):371-7.
El Atrash A, Tousson E, Gad A, Allam S. Hematological and biochemical changes caused by antidepressants amitriptyline induced cardiac toxicity in male rats. Asian Journal of Cardiology Research. 2019;23: 1-6.
Kabel AM, Abdel-Rahman MN, El-Sisi A, Haleem, MS, Ezzat NM, El Rashidy MA. Effect of atorvastatin and methotrexate on solid ehrlich tumor. Eur J Pharmacol. 2013; 713(13):47-53.
Mutar TF, Gazia MA, Salem SB, Hammed EH, Tousson E. Ehrlich ascites carcinoma bearing mice as model of human hepatocellular carcinoma. Asian Journal of Research and Reports in Hepatology. 2019;18:1-9.
Zhu FM, Du B, Li J. Effect of ultrafine grinding on physicochemical and antioxidant properties of dietary fiber from wine grape pomace. Food Sci Technol Int. 2014;20:55–62.
Zhen J, Qu Z, Fang H, Fu L, Wu Y, Wang H, Zang H, Wang W. Effects of grape seed proanthocyanidin extract on pentylenetetrazole-induced kindling and associated cognitive impairment in rats. Int J Mol Med. 2014;34:391–398.
Zhou K, Raffoul JJ. Potential anticancer properties of grape antioxidants. J Oncol, 2015;803294.
Dinicola S, Pasqualato A, Cucina A, et al. Grape seed extract suppresses MDA-MB231 breast cancer cell migration and invasion. European Journal of Nutrition. 2014;53(2):421–431.
DOI: 10.1007/s00394-013-0542-6
Leon-Cabrera S, Schwertfeger KL, Terrazas LI. Inflammation as a target in cancer therapy. Mediators of inflammation. 2019;49. Medhat D, Hussein J, El- Naggarb ME, Attia MF, Anwar M, et al. Effect of Au-dextran NPs as anti-tumor agent against EAC and solid tumor in mice by biochemical evaluations and histopathological investigations. Biomedicine & Pharmacotherapy. 2017;91: 1006–1016
Guo F, Hu Y, Niu Q, Li Y, Ding Y, Ma R, Wang X, Li S, Xie J. Grape seed proanthocyanidin extract inhibits human esophageal squamous cancerous cell line eca109 via the nf-κb signaling pathway. Mediators of Inflammation; 2018.
Lazarevich NL. Biochemistry (Mosc). 2000; 65(1):117-33.
Choi WT, Kakar S. Immunohistochemistry in the diagnosis of hepatocellular carcinoma. Gastroenterology Clinics. 2017; 46(2):311-25.
Shin M, Moon J. Effect of dietary supplementation of grape skin and seeds on liver fibrosis induced by dimethylnitrosamine in rats. Nutr Res Prac. 2010;4(5):369-374.
Del Bas JM, Fernández-Larrea J, Blay M, Ardèvol A, Salvadó MJ, Arola L, Bladé C. Grape seed procyanidins improve atherosclerotic risk index and induce liver CYP7A1 and SHP expression in healthy rats. The FASEB Journal. 2005;19(3):479-81.
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