Re-evaluation of the anticarcinogenic effect of metformin in a chemically-induced hepatocellular carcinoma model not associated with diabetes

References

• Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7(1):6.
   PubMed Web of Science ®Google Scholar
• Ferlay J, Colombet M, Soerjomataram I, et al. Cancer statistics for the year 2020: an overview. Int J Cancer. 2021 Aug 15; 149(4):778–789.
   Web of Science ®Google Scholar
• Zhang HH, Zhang Y, Cheng YN, et al. Metformin incombination with curcumin inhibits the growth, metastasis, and angiogenesis of hepatocellular carcinoma in vitro and in vivo. Mol Carcinog. 2018 Jan;57(1):44–56.
   PubMed Web of Science ®Google Scholar
• Kumari R, Sahu MK, Tripathy A, et al. Hepatocellular carcinoma treatment: hurdles, advances and prospects. Hepatic Oncol. 2018 Sep 28;5(2): HEP08.
   Web of Science ®Google Scholar
• Ikeda M, Morizane C, Ueno M, et al. Chemotherapy for hepatocellular carcinoma: current status and future perspectives. Jpn J Clin Oncol. 2018 Feb 1; 48(2):103–114.
   Web of Science ®Google Scholar
• Ma Z, Xu L, Liu D, et al. Utilizing melatonin to alleviate side effects of chemotherapy: a potentially good partner for treating cancer with ageing. Oxid Med Cell Longev. 2020 May 21;2020:1–20.
   Web of Science ®Google Scholar
• Majolo F, Delwing LK, Marmitt DJ, et al. Medicinal plants and bioactive natural compounds for cancer treatment: important advances for drug discovery. Phytochem Lett. 2019 Jun 1; 31:196–207.
   Web of Science ®Google Scholar
• Kim A, Ha J, Kim J, et al. Natural products for pancreatic cancer treatment: from traditional medicine to modern drug discovery. Nutrients. 2021 Oct 26;13(11):3801. PMID: 34836055; PMCID: PMC8625071.
   Web of Science ®Google Scholar
• Eroglu E, Uzun O. Is metformin a treatment opportunity for colorectal cancer?2020
   Google Scholar
• Saraei P, Asadi I, Kakar MA, et al. The beneficial effects of metformin on cancer prevention and therapy: a comprehensive review of recent advances. Cancer Manag Res. 2019;11:3295.
   PubMed Web of Science ®Google Scholar
• Chen YC, Li H, Wang J. Mechanisms of metformin inhibiting cancer invasion and migration. Am J Transl Res. 2020;12(9):4885.
   Web of Science ®Google Scholar
• Memmott RM, Mercado JR, Maier CR, et al. Metformin prevents tobacco carcinogen–induced lung tumorigenesis. Cancer Prev Res. 2010 Sep 1; 3(9):1066–1076.
   Web of Science ®Google Scholar
• Pateliya B, Burade V, Goswami S. Combining naringenin and metformin with doxorubicin enhances anticancer activity against triple-negative breast cancer in vitro and in vivo. Eur J Pharmacol. 2021 Jan 15;891:173725. Epub 2020 Nov 3. PMID: 33157041.
   Web of Science ®Google Scholar
• Yang J, Zhou Y, Xie S, et al. Metformin induces Ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer. J Exp Clin Cancer Res. 2021 Jun 23;40(1):206. PMID: 34162423; PMCID: PMC8223374.
   Web of Science ®Google Scholar
• Henderson D, Frieson D, Zuber J, et al. Metformin has positive therapeutic effects in colon cancer and lung cancer. Am J Med Sci. 2017 Sep 1; 354(3):246–251.
   Web of Science ®Google Scholar
• De A, Kuppusamy G. Metformin in breast cancer: preclinical and clinical evidence. Curr Probl Cancer. 2020 Feb 1; 44(1):100488.
   Web of Science ®Google Scholar
• Ugwueze CV, Ogamba OJ, Young EE, et al. Metformin: a possible option in cancer chemotherapy. Anal Cell Pathol (Amst). 2020 Apr 27;2020:7180923. PMID: 32399389; PMCID: PMC7201450.
   Google Scholar
• Fatehi Hassanabad A, MacQueen KT. Molecular mechanisms underlining the role of metformin as a therapeutic agent in lung cancer. Cell Oncol. 2021 Feb;44(1):1–8.
   Web of Science ®Google Scholar
• Jo W, Yu ES, Chang M, et al. Metformin inhibits early stage diethylnitrosamine-induced hepatocarcinogenesis in rats. Mol Med Rep. 2016 Jan 1;13(1):146–152.
   Web of Science ®Google Scholar
• Ferretti AC, Hidalgo F, Tonucci FM, et al. Metformin and glucose starvation decrease the migratory ability of hepatocellular carcinoma cells: targeting AMPK activation to control migration. Sci Rep. 2019 Feb 26;9(1):1–4.
   Google Scholar
• Uehara T, Ainslie GR, Kutanzi K, et al. Molecular mechanisms of fibrosis-associated promotion of liver carcinogenesis. Toxicol Sci. 2013 Mar 1; 132(1):53–63.
   Web of Science ®Google Scholar
• Tsai HH, Lai HY, Chen YC, et al. Metformin promotes apoptosis in hepatocellular carcinoma through the CEBPD-induced autophagy pathway. Oncotarget. 2017 Feb 21; 8(8):13832.
   Google Scholar
• Shin JW, Seol IC, Son CG. Interpretation of animal dose and human equivalent dose for drug development. J Korean Med. 2010;31(3):1–7.
   Google Scholar
• Garabadu D, Krishnamurthy S. Diazepam potentiates the antidiabetic, antistress and anxiolytic activities of metformin in type-2 diabetes mellitus with cooccurring stress in experimental animals. Biomed Res Int. 2014 Jun 4;2014:1–15.
   Web of Science ®Google Scholar
• Chukwunonso Obi B, Chinwuba Okoye T, Okpashi VE, et al. Comparative study of the antioxidant effects of metformin, glibenclamide, and repaglinide in alloxan-induced diabetic rats. J Diabetes Res. 2016;2016:1–5.
   Web of Science ®Google Scholar
• Shivavedi N, Kumar M, Tej GN, et al. Metformin and ascorbic acid combination therapy ameliorates type 2 diabetes mellitus and comorbid depression in rats. Brain Res. 2017 Nov 1;1674:1–9
   Web of Science ®Google Scholar
• Song CW, Lee H, Dings RP, et al. Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells. Sci Rep. 2012 Apr 12;2(1):1–9.
   Google Scholar
• Gamble, M. The Hematoxylin and Eosin Theory and practice of histological techniques 6th. Bancroft JD, Gamble M, editors. Churchill Livingstone, Oxford: Elsevier health sciences. 2008;121–134.
   Google Scholar
• Mohr U, editor. International classification of rodent tumors: the mouse. Berlin: Springer; 2001.
   Google Scholar
• Crocker J, Nar P, Song CW, et al. Nucleolar organizer regions in lymphomas. J Pathol. 1987;151(2):111–118.
   PubMed Web of Science ®Google Scholar
• Nonomura A, Mizukami Y, Matsubara F, et al. Identification of nucleolar organizer regions in non‐neoplastic and neoplastic hepatocytes by the silver‐staining technique. Liver. 1990;10(4):229–238.
   Google Scholar
• Luo M, Yang F, Huang SX, et al. Two-stage model of chemically induced hepatocellular carcinoma in mouse. Oncol Res. 2013;20(11):517–528.
   Web of Science ®Google Scholar
• Fathy AH, Bashandy MA, Bashandy SA, et al. Sequential analysis and staging of a diethylnitrosamine-induced hepatocellular carcinoma in male Wistar albino rat model. Can J Physiol Pharmacol. 2017;95(12):1462–1472.
   Web of Science ®Google Scholar
• Tripathy A, Thakurela S, Sahu MK, et al. Fatty changes associated with N-Nitrosodiethylamine (DEN) induced hepatocellular carcinoma: a role of sonic hedgehog signaling pathway. Genes Cancer. 2020;11(1–2):66–82.
   Google Scholar
• Hussein SA, Abdel-Aal SA, Mady HA. Spirullina inhibit the development of diethylnitrosamine induced premalignant phenotype in rat chemical hepatocarcinogenesis model. BENHA VET MED J. 2018 Dec 1; 35(2):650–661.
   Google Scholar
• Thomas SV, Paul J, Shrungeswara AH, et al. Annona muricata fruit extract protects against diethylnitrosamine-induced hepatocellular cancer in rats. Asian Pac J Trop Med. 2019 Jun 1;12(6):272.
   Web of Science ®Google Scholar
• Sarkar S, Bhattacharjee P, Ghosh T, et al. Pharmaceutical efficacy of harmalol in inhibiting hepatocellular carcinoma. Future J Pharm Sci. 2020 Dec;6(1):1–8.
   Web of Science ®Google Scholar
• Taïbi N, Al-Balas QA, Bekari N, et al. Molecular docking and dynamic studies of a potential therapeutic target inhibiting glyoxalase system: metabolic action of the 3, 3’-[3-(5-chloro-2-hydroxyphenyl)-3-oxopropane-1, 1-diyl]-Bis-4-hydroxycoumarin leads overexpression of the intracellular level of methylglyoxal and induction of a pro-apoptotic phenomenon in a hepatocellular carcinoma model. Chem Biol Interact. 2021 Aug 25; 345:109511
   Web of Science ®Google Scholar
• Zhang W, Zhangyuan G, Wang F, et al. High preoperative serum globulin in hepatocellular carcinoma is a risk factor for poor survival. J Cancer. 2019;10(15):3494.
   Web of Science ®Google Scholar
• Abouzed TK, Althobaiti F, Abdelkhlek NA, et al. Antitumor and antioxidant activity of S-methyl methionine sulfonium chloride against liver cancer induced in Wistar Albino rats by diethyl nitrosamine and carbon tertrachloride. Int J Environ Res Public Health. 2021 Jan;18(18):9726.
   Web of Science ®Google Scholar
• Zheng X, Zhou Y, Yi X, et al. IL-21 receptor signaling is essential for control of hepatocellular carcinoma growth and immunological memory for tumor challenge. Oncoimmunology. 2018 Dec 2;7(12):e1500673.
   Web of Science ®Google Scholar
• Wen J, Chen X, Wei S, et al. Research progress and treatment status of liver cirrhosis with hypoproteinemia. Evid Based Complement Alternat Med. 2022 Feb 24;2022:1–8.
   Web of Science ®Google Scholar
• Zakhary NI, El Gemeie EE, Youssef AK, et al. Flavonoids content of 70% methanolic extract of Erucaria pinnata (Viv.) and its effect as anticancer and antiangiognic: in vitro, in vivo and docking study.
   Google Scholar
• Taha H, Elfar N, Haffez H, et al. Raptinal silver nanoparticles: new therapeutic advances in hepatocellular carcinoma mouse model. Naunyn-Schmiedeberg’s Arch Pharmacol. 2021 Feb;394(2):279–289.
   Google Scholar
• Zhang HH, Zhang Y, Cheng YN, et al. Metformin incombination with curcumin inhibits the growth, metastasis, and angiogenesis of hepatocellular carcinoma in vitro and in vivo. Mol Carcinog. 2018 Jan;57(1):44–56.
   PubMed Web of Science ®Google Scholar
• Al-Salih HA, Al-Sharafi NM, Al-Qabi SS, et al. The Pathological Features of cyclophosphamide induced multi-organs toxicity in male wister rats. Sys Rev Pharm. 2020 Jun 1;11(6):45–49.
   Google Scholar
• Babaei G, Aliarab A, Abroon S, et al. Application of sesquiterpene lactone: a new promising way for cancer therapy based on anticancer activity. Biomed Pharmacother. 2018 Oct;106:239–246 Epub 2018 Jun 28. PMID: 29966966
   PubMed Web of Science ®Google Scholar
• Lee MS, Hsu CC, Wahlqvist ML, et al. Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals. BMC Cancer. 2011 Dec;11(1):1.
   Google Scholar
• Bhalla K, Hwang BJ, Dewi RE, et al. Metformin prevents liver tumorigenesis by inhibiting pathways driving hepatic lipogenesis. Cancer Prev Res. 2012;5(4):544–552.
   PubMed Web of Science ®Google Scholar
• Park JW, Lee JH, Park YH, et al. Sex-dependent difference in the effect of metformin on colorectal cancer-specific mortality of diabetic colorectal cancer patients. World J Gastroenterol. 2017 Jul 28;23(28):5196.
   Web of Science ®Google Scholar
• Brackett CC. Clarifying metformin’s role and risks in liver dysfunction. J Am Pharm Assoc. 2010 May 1;50(3):407–410.
   Google Scholar
• Nguyen HL, Concepcion L. Metformin intoxication requiring dialysis. Hemodialysis Int. 2011 Oct;15:S68–71.
   Web of Science ®Google Scholar
• Salvatore T, Pafundi PC, Marfella R, et al. Metformin lactic acidosis: should we still be afraid? Diabetes Res Clin Pract. 2019 Nov 1;157:107879
   Web of Science ®Google Scholar
• Miao P, Sheng S, Sun X, et al. Lactate dehydrogenase A in cancer: a promising target for diagnosis and therapy. IUBMB Life. 2013 Nov;65(11):904–910.
   PubMed Web of Science ®Google Scholar
• DeFronzo R, Fleming GA, Chen K, et al. Metformin-associated lactic acidosis: current perspectives on causes and risk. Metabolism. 2016 Feb 1;65(2):20–29.
   Web of Science ®Google Scholar
• DePeralta DK, Wei L, Ghoshal S, et al. Metformin prevents hepatocellular carcinoma development by suppressing hepatic progenitor cell activation in a rat model of cirrhosis. Cancer. 2016 Apr 15;122(8):1216–1227.
   Web of Science ®Google Scholar
• Das BK, Choukimath SM, Gadad PC. Asarone and metformin delays experimentally induced hepatocellular carcinoma in diabetic milieu. Life Sci. 2019 Aug 1;230:10–18.
   Web of Science ®Google Scholar
• Mobasher MA, El-Tantawi HG, El-Said KS. Metformin ameliorates oxidative stress induced by diabetes mellitus and hepatocellular carcinoma in rats. Rep Biochem Mol Biol. 2020 Apr;9(1):115.
   Web of Science ®Google Scholar