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The Anticarcinogenic Effect of the Apple Polyphenol Phloretin in an Experimental Rat Model of Hepatocellular Carcinoma

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Abstract

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide, probably because of late diagnosis and lack of treatment. There is a great need to discover a novel compound to improve the general prognosis of HCC. Phloretin (Ph) is an apple polyphenol that is effective in treating pathogenic conditions having oxidative stress as a common mechanism. This study evaluated the anticancer property of Ph. Comparison of the Ph group with the HCC group indicated that Ph supplementation helped improve serum biomarkers of liver cancer, liver functions and oxidative status and enhance histological and morphological appearance and gene expression. Our results clearly demonstrated that Ph supplementation induced an apparent chemopreventive effect against diethylnitrosamine-induced HCC, as manifested by a significant modulation of serum biomarkers of liver cancer, liver functions, oxidative status, along with restraining histological appearance and gene expression.

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References

  1. Shire, A.M.; Roberts, L.R.: Prevention of hepatocellular carcinoma: progress and challenges. Minerva Gastroenterol. Dietol. 58, 49–64 (2012)

    Google Scholar 

  2. Maluccio, M.; Covey, A.: Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma. CA Cancer J. Clin. 62, 394–399 (2012)

    Article  Google Scholar 

  3. Marra, M.; Sordelli, I.M.; Lombardi, A.; Lamberti, M.; Tarantino, L.; Giudice, A.; Stiuso, P.; Abbruzzese, A.; Sperlongano, R.; Accardo, M.; Agresti, M.: Molecular targets and oxidative stress biomarkers in hepatocellular carcinoma: an overview. J. Transl. Med. 9, 171 (2011)

    Article  Google Scholar 

  4. White, D.L.; Kanwal, F.; El-Serag, H.B.: Association between non-alcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin. Gastroenterol. Hepatol. 10, 1342–1359 (2012)

    Article  Google Scholar 

  5. Hong, M.; Li, S.; Tan, H.; Wang, N.; Tsao, S.W.; Feng, Y.: Current status of herbal medicines in chronic liver disease therapy: the biological effects, molecular targets and future prospects. Int. J. Mol. Sci. 16, 28705–28745 (2015)

    Article  Google Scholar 

  6. Liu, Y.; Wu, F.: Global burden of aflatoxin-induced hepatocellular carcinoma: a risk assessment. Environ. Health Perspect. 118, 818–824 (2010)

    Article  Google Scholar 

  7. Balogh, J.; David Victor III, E.H.; Burroughs, S.G.; Boktour, M.; Saharia, A.; Li, X.; Ghobrial, R.M.; Monsour Jr., H.P.: Hepatocellular carcinoma: a review. J. Hepatocell. Carcinoma 3, 41 (2016)

    Article  Google Scholar 

  8. Xiao, W.; Zhao, S.; Shen, F.; Liang, J.; Chen, J.: Overexpression of CD147 is associated with poor prognosis, tumor cell migration and ERK signaling pathway activation in hepatocellular carcinoma. Exp. Ther. Med. 14, 2637–2642 (2017)

    Article  Google Scholar 

  9. Chen, J.C.; Chuang, H.Y.; Hsu, F.T.; Chen, Y.C.; Chien, Y.C.; Hwang, J.J.: Sorafenib pretreatment enhances radiotherapy through targeting MEK/ERK/NF-κB pathway in human hepatocellular carcinoma-bearing mouse model. Oncotarget 7, 85450 (2016)

    Article  Google Scholar 

  10. Mormone, E.; George, J.; Nieto, N.: Molecular pathogenesis of hepatic fibrosis and current therapeutic approaches. Chem. Biol. Interact. 193, 225–231 (2011)

    Article  Google Scholar 

  11. Srinivasan, K.: Antimutagenic and cancer preventive potential of culinary spices and their bioactive compounds. Pharma Nutrition 5, 89–102 (2017)

    Article  Google Scholar 

  12. Choi, B.Y.: Biochemical basis of anti-cancer-effects of phloretin-a natural dihydrochalcone. Molecules 24, 278 (2019)

    Article  Google Scholar 

  13. Ribes, J.; Clèries, R.; Esteban, L.; Moreno, V.; Bosch, F.X.: The influence of alcohol consumption and hepatitis B and C infections on the risk of liver cancer in Europe. J. Hepatol. 49, 233–242 (2008)

    Article  Google Scholar 

  14. Malinowska, M.; Sliwa, K.; Sikora, E.; Ogonowski, J.; Oszmiánski, J.; Kolniak-Ostek, J.: Ultrasound-assisted and micelle-mediated extraction as a method to isolate valuable active compounds from apple pomace. J. Food Process. Preserve 42, e13720 (2018)

    Article  Google Scholar 

  15. Gerhauser, C.: Cancer chemopreventive potential of apples, apple juice, and apple components. Planta Med. 74, 1608e24 (2008)

    Article  Google Scholar 

  16. Tamura, Y.; Tomiya, S.; Takegaki, J.; Kouzaki, K.; Tsutaki, A.; Nakazato, K.: Apple polyphenols induce browning of white adipose tissue. J. Nutr. Biochem. 77, 108299 (2020)

    Article  Google Scholar 

  17. Ma, L.; Wang, R.; Nan, Y.; Li, W.; Wang, Q.; Jin, F.: Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases. Int. J. Oncol. 48, 843–853 (2016)

    Article  Google Scholar 

  18. de Oliveira, M.R.: Phloretin-induced cytoprotective effects on mammalian cells: a mechanistic view and future directions. Bio Factors 42, 13–40 (2016)

    Google Scholar 

  19. Kim, U.; Kim, C.Y.; Lee, J.M.; Oh, H.; Ryu, B.; Kim, J.; Park, J.H.: Phloretin inhibits the human prostate cancer cells through the generation of reactive oxygen species. Pathol. Oncol. Res. 1, 1–8 (2019)

    Google Scholar 

  20. Shin, J.W.; Kundu, J.K.; Surh, Y.J.: Phloretin inhibits phorbol ester-induced tumor promotion and expression of cyclooxygenase-2 in mouse skin: extracellular signal-regulated kinase and nuclear factor-κB as potential targets. J. Med. Food 15, 253–257 (2012)

    Article  Google Scholar 

  21. Crespy, V.; Aprikian, O.; Morand, C.; Besson, C.; Manach, C.; Demigné, C.; Rémésy, C.: Bioavailability of phloretin and phloridzin in rats. J. Nutr. 131, 3227–3230 (2001)

    Article  Google Scholar 

  22. Yang, N.; Ekanem, N.R.; Sakyi, C.A.; Ray, S.D.: Hepatocellular carcinoma and microRNA: new perspectives on therapeutics and diagnostics. Adv. Drug Deliv. Rev. 81, 62–74 (2015)

    Article  Google Scholar 

  23. Subramaniam, N.; Kannan, P.; Ashokkumar, K.; Thiruvengadam, D.: Hepatoprotective effect of boldine against diethylnitrosamine-induced hepatocarcinogenesis in wistar rats. J. Biochem. Mol. Toxicol. 33(12), e22404 (2019)

    Article  Google Scholar 

  24. Liao, D.J.; Blanck, A.; Eneroth, P.; Gustafsson, J.A.; Hällström, I.P.: Diethylnitrosamine causes pituitary damage, disturbs hormone levels, and reduces sexual dimorphism of certain liver functions in the rat. Environ. Health Perspect. 10, 943–947 (2001)

    Article  Google Scholar 

  25. Shirakami, Y.; Gottesman, M.E.; Blaner, W.S.: Diethylnitrosamine-induced hepatocarcinogenesis is suppressed in lecithin: retinol acyltransferase-deficient mice primarily through retinoid actions immediately after carcinogen administration. Carcinogenesis 33, 268–274 (2011)

    Article  Google Scholar 

  26. Karimov, K.Y.; Inoyatova, F.; Mukhamedova, M.T.: Changes in some indices of the synthesis of nitric oxide during the early stages of hepatocarcinogenesis. Exp. Toxicol. Pathol. 55, 17–19 (2003)

    Article  Google Scholar 

  27. Arafa, M.H.; Mohammad, N.S.; Atteia, H.H.; Abd-Elaziz, H.R.: Protective effect of resveratrol against doxorubicin-induced cardiac toxicity and fibrosis in male experimental rats. J. Physiol. Biochem. 70, 701–711 (2014)

    Article  Google Scholar 

  28. Balaha, M.; Kandeel, S.; Kabel, A.: Phloretin either alone or in combination with duloxetine alleviates the STZ-induced diabetic neuropathy in rats. Biomed. Pharmacother. 101, 821–832 (2018)

    Article  Google Scholar 

  29. Amin, A.; Hamza, A.A.; Bajbouj, K.; Ashraf, S.S.; Daoud, S.: Saffron: a potential candidate for a novel anticancer drug against hepatocellular carcinoma. Hepatology 54, 857–867 (2011)

    Article  Google Scholar 

  30. Ahadpour, M.; Eskandari, M.R.; Mashayekhi, V.; Haj Mohammad Ebrahim Tehrani, K.; Jafarian, I.; Naserzadeh, P.; Hosseini, M.J.: Mitochondrial oxidative stress and dysfunction induced by isoniazid: study on isolated rat liver and brain mitochondria. Drug Chem. Toxicol. 39, 224–232 (2016)

    Article  Google Scholar 

  31. Livak, K.J.; Schmittgen, T.D.: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C (T)) Method). Methods 25, 402–408 (2001)

    Article  Google Scholar 

  32. Tajadini, M.; Panjehpour, M.; Javanmard, S.H.: Comparison of SYBR Green and TaqMan methods in quantitative real-time polymerase chain reaction analysis of four adenosine receptor subtypes. Adv. Biomed. Res. 3, 85 (2014)

    Article  Google Scholar 

  33. El-Sayyad, H.I.; Ismail, M.F.; Shalaby, F.M.; Abou-El-Magd, R.F.; Gaur, R.L.; Fernando, A.; Raj, M.H.; Ouhtit, A.: Histopathological effects of cisplatin, doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats. Int. J. Biol. Sci. 5, 466 (2009)

    Article  Google Scholar 

  34. Xin, B.; Cui, Y.; Wang, Y.; Wang, L.; Yin, J.; Zhang, L.; Pang, H.; Zhang, H.; Wang, R.A.: Combined use of alcohol in conventional chemical–induced mouse liver cancer model improves the simulation of clinical characteristics of human hepatocellular carcinoma. Oncol. Lett. 14, 4722–4728 (2017)

    Article  Google Scholar 

  35. Hamza, A.A.; Heeba, G.H.; Elwy, H.M.; Murali, C.; El-Awady, R.; Amin, A.: Molecular characterization of the grape seeds extract’s effect against chemically induced liver cancer: in vivo and in vitro analyses. Sci. Rep. 8, 1270 (2018)

    Article  Google Scholar 

  36. Ramakrishnan, G.; Augustine, T.A.; Jagan, S.; Vinodhkumar, R.; Devaki, T.: Effect of silymarin on N-nitrosodiethylamine induced hepatocarcinogenesis in rats. Exp. Oncol. 29(1), 39–44 (2007)

    Google Scholar 

  37. Arslan, A.; Demir, H.; Ozbay, M.F.; Arslan, H.: Evaluation of lipid peroxidation and some antioxidant activities in patients with primary and metastatic liver cancer. J. Cancer Therapy 5, 192 (2014)

    Article  Google Scholar 

  38. Muresan, A.; Suciu, S.; Clichici, S.; Daicoviciu, D.; Pop, N.: Study on the effects of grape seed extract in ehrlich ascitic carcinoma. Bull. Univ. Agric. Sci. Vet. Med. Cluj-Napoca Vet. Med. 63(1–2) (2006)

  39. Ren, D.; Zhao, Y.; Nie, Y.; Yang, N.; Yang, X.: Hypoglycemic and hepatoprotective effects of polysaccharides from Artemisia sphaerocephala Krasch seeds. Int. J. Biol. Macromol. 69, 296–306 (2014)

    Article  Google Scholar 

  40. Erejuwa, O.O.; Sulaiman, S.A.; Wahab, M.S.; Sirajudeen, K.N.; Salleh, M.S.; Gurtu, S.: Hepatoprotective effect of tualang honey supplementation in streptozotocin-induced diabetic rats. Int. J. Appl. Res. Nat. Prod. 4, 37–41 (2012)

    Google Scholar 

  41. Tanabe, K.K.; Lemoine, A.; Finkelstein, D.M.; Kawasaki, H.; Fujii, T.; Chung, R.T.; Lauwers, G.Y.; Kulu, Y.; Muzikansky, A.; Kuruppu, D.; Lanuti, M.: Epidermal growth factor gene functional polymorphism and the risk of hepatocellular carcinoma in patients with cirrhosis. JAMA 299, 53–60 (2008)

    Article  Google Scholar 

  42. Weber, L.W.; Boll, M.; Stampfl, A.: Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit. Rev. Toxicol. 33, 105–136 (2003)

    Article  Google Scholar 

  43. Zhang, R.; Zhao, Y.; Sun, Y.; Lu, X.; Yang, X.: Isolation, characterization, and hepatoprotective effects of the raffinose family oligosaccharides from Rehmannia glutinosa Libosch. J. Agric. Food Chem. 61, 7786–7793 (2013)

    Article  Google Scholar 

  44. Geohagen, B.C.; Vydyanathan, A.; Kosharskyy, B.; Shaparin, N.; Gavin, T.; LoPachin, R.M.: Enolate-forming phloretin pharmacophores: hepatoprotection in an experimental model of drug-induced toxicity. J. Pharmacol. Exp. Ther. 357, 476–486 (2016)

    Article  Google Scholar 

  45. Zessner, H.; Pan, L.; Will, F.; Klimo, K.; Knauft, J.; Niewöhner, R.; Hümmer, W.; Owen, R.; Richling, E.; Frank, N.; Schreier, P.: Fractionation of polyphenol-enriched apple juice extracts to identify constituents with cancer chemopreventive potential. Mol. Nutr. Food Res. 52, S28–S44 (2008)

    Google Scholar 

  46. Yang, J.; Li, Y.; Wang, F.; Wu, C.: Hepatoprotective effects of apple polyphenols on CCl4-induced acute liver damage in mice. J. Agric. Food Chem. 58, 6525–6531 (2010)

    Article  Google Scholar 

  47. Zhang, C.L.; Zeng, T.; Zhao, X.L.; Yu, L.H.; Zhu, Z.P.; Xie, K.Q.: Protective effects of garlic oil on hepatocarcinoma induced by N-nitrosodiethylamine in rats. Int. J. Biol. Sci. 8, 363 (2012)

    Article  Google Scholar 

  48. Jayaprakasha, G.K.; Selvi, T.; Sakariah, K.K.: Antibacterial and antioxidant activities of grape (Vitis vinifera) seed extracts. Food Res. Int. 36, 117–122 (2003)

    Article  Google Scholar 

  49. Klaunig, J.E.; Kamendulis, L.M.: The role of oxidative stress in carcinogenesis. Annu. Rev. Pharmacol. Toxicol. 44, 239–267 (2004)

    Article  Google Scholar 

  50. Yang, Y.C.; Lii, C.K.; Lin, A.H.; Yeh, Y.W.; Yao, H.T.; Li, C.C.; Liu, K.L.; Chen, H.W.: Induction of glutathione synthesis and heme oxygenase 1 by the flavonoids butein and phloretin is mediated through the ERK/Nrf2 pathway and protects against oxidative stress. Free Radic. Biol. Med. 51, 2073–2081 (2011)

    Article  Google Scholar 

  51. Wang, L.; Pan, L.; Yao, M.; Cai, Y.; Dong, Z.; Yao, D.: Expression of oncofetal antigen glypican-3 associates significantly with poor prognosis in HBV-related hepatocellular carcinoma. Oncotarget 7, 42150 (2016)

    Article  Google Scholar 

  52. Filmus, J.; Selleck, S.B.: Glypicans: proteoglycans with a surprise. J. Clin. Investig. 108, 497–501 (2001)

    Article  Google Scholar 

  53. Yao, M.; Wang, L.; Fang, M.; Zheng, W.; Dong, Z.; Yao, D.: Advances in the study of oncofetal antigen glypican-3 expression in HBV-related hepatocellular carcinoma. Biosci. Trends 10, 337–343 (2016)

    Article  Google Scholar 

  54. Haruyama, Y.; Kataoka, H.: Glypican-3 is a prognostic factor and an immunotherapeutic target in hepatocellular carcinoma. World J. Gastroenterol. 22, 275 (2016)

    Article  Google Scholar 

  55. Zhu, Z.W.; Friess, H.; Wang, L.; Abou-Shady, M.; Zimmermann, A.; Lander, A.D.; Korc, M.; Kleeff, J.; Büchler, M.W.: Enhanced glypican-3 expression differentiates the majority of hepatocellular carcinomas from benign hepatic disorders. Gut 48, 558–564 (2001)

    Article  Google Scholar 

  56. Vasantha Rupasinghe, H.; Yasmin, A.: Inhibition of oxidation of aqueous emulsions of omega-3 fatty acids and fish oil by phloretin and phloridzin. Molecules 15, 251–257 (2010)

    Article  Google Scholar 

  57. Chao, Y.; Li, C.P.; Chau, G.Y.; Chen, C.P.; King, K.L.; Lui, W.Y.; Yen, S.H.; Chang, F.Y.; Chan, W.K.; Lee, S.D.: Prognostic significance of vascular endothelial growth factor, basic fibroblast growth factor, and angiogenin in patients with resectable hepatocellular carcinoma after surgery. Ann. Surg. Oncol. 10, 355–362 (2003)

    Article  Google Scholar 

  58. Xiang, Z.L.; Zeng, Z.C.; Fan, J.; Tang, Z.Y.; Zeng, H.Y.; Gao, D.M.: Gene expression profiling of fixed tissues identified hypoxia-inducible factor-1α, VEGF, and matrix metalloproteinase-2 as biomarkers of lymph node metastasis in hepatocellular carcinoma. Clin. Cancer Res. 17, 5463–5472 (2011)

    Article  Google Scholar 

  59. Perkins, G.L.; Slater, E.D.; Sanders, G.K.; Prichard, J.G.: Serum tumor markers. Am. Fam. Physician 68, 1075–1088 (2003)

    Google Scholar 

  60. Park, I.J.; Kim, H.C.; Yu, C.S.; Yoo, J.H.; Kim, J.C.: Cutoff values of preoperative s-CEA levels for predicting survivals after curative resection of colorectal cancer. J. Korean Med. Sci. 20, 624–627 (2005)

    Article  Google Scholar 

  61. Majewska, M.; Lewandowska, U.: The chemopreventive and anticancer potential against colorectal cancer of polyphenol-rich fruit extracts. Food Rev. Int. 34, 390–409 (2018)

    Article  Google Scholar 

  62. Breindel, J.L.; Haskins, J.W.; Cowell, E.P.; Zhao, M.; Nguyen, D.X.; Stern, D.F.: EGF receptor activates MET through MAP kinases to enhance non-small cell lung carcinoma invasion and brain metastasis. Can. Res. 73(16), 5053–5065 (2013)

    Article  Google Scholar 

  63. Shehata, F.; Monem, N.A.; Sakr, M.; Kasem, S.; Balbaa, M.: Epidermal growth factor, its receptor and transforming growth factor-β1 in the diagnosis of HCV-induced hepatocellular carcinoma. Med. Oncol. 30, 673 (2013)

    Article  Google Scholar 

  64. Budhu, A.; Wang, X.W.: The role of cytokines in hepatocellular carcinoma. J. Leukoc. Biol. 80, 1197–1213 (2006)

    Article  Google Scholar 

  65. Cheng, N.; Ren, N.; Gao, H.; Lei, X.; Zheng, J.; Cao, W.: Antioxidant and hepatoprotective effects of Schisandra chinensis pollen extract on CCl4-induced acute liver damage in mice. Food Chem. Toxicol. 55, 234–240 (2013)

    Article  Google Scholar 

  66. Garcia, M.C.; Amankwa-Sakyi, M.; Flynn, T.J.: Cellular glutathione in fatty liver in vitro models. Toxicol. In Vitro 25, 1501–1506 (2011)

    Article  Google Scholar 

  67. Vora, S.R.; Zheng, H.; Stadler, Z.K.; Fuchs, C.S.; Zhu, A.X.: Serum α-fetoprotein response as a surrogate for clinical outcome in patients receiving systemic therapy for advanced hepatocellular carcinoma. Oncologist 14, 717–725 (2009)

    Article  Google Scholar 

  68. Othman, A.M.; El-Houseini, M.E.; El-Sofy, M.S.; Aboul-Enein, H.Y.: Potentiometric determination of α-L-fucosidase enzyme by using 2-chloro-4-nitrophenol-rhodamine B ion pair chemical recognition in PVC membrane sensor. Anal. Bioanal. Chem. 400, 787–795 (2011)

    Article  Google Scholar 

  69. Nakatsura, T.; Yoshitake, Y.; Senju, S.; Monji, M.; Komori, H.; Motomura, Y.; Hosaka, S.; Beppu, T.; Ishiko, T.; Kamohara, H.; Ashihara, H.: Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker. Biochem. Biophys. Res. Commun. 306, 16–25 (2003)

    Article  Google Scholar 

  70. Sivaramakrishnan, V.; Devaraj, S.N.: Morin fosters apoptosis in experimental hepatocellular carcinogenesis model. Chem. Biol. Interact. 183, 284–292 (2010)

    Article  Google Scholar 

  71. Jaganathan, S.K.; Vellayappan, M.V.; Narasimhan, G.; Supriyanto, E.; Dewi, D.E.; Narayanan, A.L.; Balaji, A.; Subramanian, A.P.; Yusof, M.: Chemopreventive effect of apple and berry fruits against colon cancer. World J. Gastroenterol. WJG 20, 17029 (2014)

    Article  Google Scholar 

  72. Wu, C.H.; Ho, Y.S.; Tsai, C.Y.; Wang, Y.J.; Tseng, H.; Wei, P.L.; Lee, C.H.; Liu, R.S.; Lin, S.Y.: In vitro and in vivo study of phloretin-induced apoptosis in human liver cancer cells involving inhibition of type II glucose transporter. Int. J. Cancer 124, 2210–2219 (2009)

    Article  Google Scholar 

  73. Duan, H.; Wang, R.; Yan, X.; Liu, H.; Zhang, Y.; Mu, D.; Han, J.; Li, X.: Phloretin induces apoptosis of human esophageal cancer via a mitochondria-dependent pathway. Oncol. Lett. 14, 6763–6768 (2017)

    Article  Google Scholar 

  74. D’Argenio, G.; Mazzone, G.; Tuccillo, C.; Ribecco, M.T.; Graziani, G.; Gravina, A.G.; Caserta, S.; Guido, S.; Fogliano, V.; Caporaso, N.; Romano, M.: Apple polyphenols extract (APE) improves colon damage in a rat model of colitis. Diges. Liver Dis. 44, 555–562 (2012)

    Article  Google Scholar 

  75. Hassanen, N.H.; Ahmed, M.H.: Protective effect of fish oil and virgin olive oil on diethylnitrosamine toxicity in rats. Int. J. Nutr. Food Sci. 4, 388–396 (2015)

    Article  Google Scholar 

  76. Borbath, I.; Stärkel, P.: Chemoprevention of hepatocellular carcinoma. Proof of concept in animal models. Acta Gastro-enterol. Bel. (English Ed) 74, 34–44 (2011)

    Google Scholar 

  77. Thoolen, B.; ten Kate, F.J.; van Diest, P.J.; Malarkey, D.E.; Elmore, S.A.; Maronpot, R.R.: Comparative histomorphological review of rat and human hepatocellular proliferative lesions. J. Toxicol. Pathol. 25, 189–199 (2012)

    Article  Google Scholar 

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  1. Biochemistry Department, Faculty of Science, University of Jeddah, Jeddah, Saudi Arabia

    Wafa S. Alansari

  2. Chemistry Department, Faculty of Science, Taibah University, Medina, Saudi Arabia

    Areej A. Eskandrani

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Alansari, W.S., Eskandrani, A.A. The Anticarcinogenic Effect of the Apple Polyphenol Phloretin in an Experimental Rat Model of Hepatocellular Carcinoma. Arab J Sci Eng 45, 4589–4597 (2020). https://doi.org/10.1007/s13369-020-04478-7

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