Testosterone Exacerbates the Formation of Liver Cancer Induced by Environmental N-Nitrosamines Exposure: Potential Mechanisms and Implications for Human Health

References

• Li YY, Wan MM, Zhu JH. Cleaning carcinogenic nitrosamines with zeolites. Environ Chem Lett. 2014;12(1):139–152. doi:10.1007/s10311-013-0451-1
   Web of Science ®Google Scholar
• Lona-Ramirez FJ, Gonzalez-Alatorre G, Rico-Ramírez V, Perez-Perez MC, Castrejón-González EO. Gas chromatography/mass spectrometry for the determination of nitrosamines in red wine. Food Chem. 2016;196:1131–1136. doi:10.1016/j.foodchem.2015.09.090
   PubMed Web of Science ®Google Scholar
• Li X, Bei E, Qiu Y, et al. Intake of volatile nitrosamines by Chinese residents in different provinces via food and drinking water. Sci Total Environ. 2021;1(754):142121. doi:10.1016/j.scitotenv.2020.142121
   Google Scholar
• Ramírez N, Özel MZ, Lewis AC, Marcé RM, Borrull F, Hamilton JF. Exposure to nitrosamines in thirdhand tobacco smoke increases cancer risk in non-smokers. Environ Int. 2014;71:139–147. doi:10.1016/j.envint.2014.06.012
   PubMed Web of Science ®Google Scholar
• Wu CC, Wang WJ, Bao LJ, Shi L, Tao S, Zeng EY. Impacts of texture properties and airborne particles on accumulation of tobacco-derived chemicals in fabrics. J Hazard Mater. 2019;369:108–115. doi:10.1016/j.jhazmat.2018.12.107
   PubMed Web of Science ®Google Scholar
• Chen Y, Chen W, Huang H, et al. Occurrence of N-nitrosamines and their precursors in the middle and lower reaches of Yangtze River water. Environ. Res. 2021;195:110673. doi:10.1016/j.envres.2020.110673
   PubMed Web of Science ®Google Scholar
• Luo Q, Bei E, Liu C, et al. Spatial, temporal variability and carcinogenic health risk assessment of nitrosamines in a drinking water system in China. Sci Total Environ. 2020;736:139695. doi:10.1016/j.scitotenv.2020.139695
   PubMed Web of Science ®Google Scholar
• Fan CC, Lin TF. N-nitrosamines in drinking water and beer: detection and risk assessment. Chemosphere. 2018;200:48–56. doi:10.1016/j.chemosphere.2018.02.025
   PubMed Web of Science ®Google Scholar
• Farren NJ, Ramírez N, Lee JD, Finessi E, Lewis AC, Hamilton JF. Estimated Exposure Risks from Carcinogenic Nitrosamines in Urban Airborne Particulate Matter. Enviro Sci Technol. 2015;49(16):9648–9656. doi:10.1021/acs.est.5b01620
   PubMed Web of Science ®Google Scholar
• Choi NR, Ahn YG, Lee JY, et al. Winter-time particulate nitrosamines and nitramines in the atmosphere at Seoul, South Korea. Atmos Environ. 2020;237:117582. doi:10.1016/j.atmosenv.2020.117582
   Web of Science ®Google Scholar
• Engemann A, Focke C, Humpf H-U. Intestinal Formation of N -Nitroso Compounds in the Pig Cecum Model. J Agr Food Chem. 2013;61(4):998–1005. doi:10.1021/jf305040e
   PubMed Web of Science ®Google Scholar
• Kobayashi J. Effect of diet and gut environment on the gastrointestinal formation of N-nitroso compounds: a review. Nitric Oxide. 2018;73:66–73. doi:10.1016/j.niox.2017.06.001
   PubMed Web of Science ®Google Scholar
• Gushgari AJ, Halden RU. Critical review of major sources of human exposure to N-nitrosamines. Chemosphere. 2018;210:1124–1136. doi:10.1016/j.chemosphere.2018.07.098
   PubMed Web of Science ®Google Scholar
• Li YS, Leng CL, Chen MT, et al. Mouse hepatic neoplasm formation induced by trace level and low frequency exposure to diethylnitrosamine through β-catenin signaling pathway. Toxicol Res. 2016;5(1):210–223. doi:10.1039/c5tx00317b
   Web of Science ®Google Scholar
• McGuire S. World Cancer Report 2014. Geneva, Switzerland: world Health Organization, International Agency for Research on Cancer, WHO Press, 2015. Adv. Nutr. 2016;7(2):418–419. doi:10.3945/an.116.012211
   PubMed Web of Science ®Google Scholar
• Paula Santos N, Colaço A, da Costa RM G, Manuel Oliveira M, Peixoto F, Alexandra Oliveira P. N-diethylnitrosamine mouse hepatotoxicity: time-related effects on histology and oxidative stress. Exp Toxicol Pathol. 2014;66(9–10):429–436. doi:10.1016/j.etp.2014.07.002
   PubMedGoogle Scholar
• Zheng B, Zhu YJ, Wang HY, Chen L. Gender disparity in hepatocellular carcinoma (HCC): multiple underlying mechanisms. Sci China Life Sci. 2017;60(6):575–584. doi:10.1007/s11427-016-9043-9
   PubMed Web of Science ®Google Scholar
• El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557–2576. doi:10.1053/j.gastro.2007.04.061
   PubMed Web of Science ®Google Scholar
• Ruggieri A, Barbati C, Malorni W. Cellular and molecular mechanisms involved in hepatocellular carcinoma gender disparity. Int j Cancer. 2010;127(3):499–504. doi:10.1002/ijc.25298
   PubMed Web of Science ®Google Scholar
• Lee C, Kim J, Han J, et al. Formyl peptide receptor 2 determines sex-specific differences in the progression of nonalcoholic fatty liver disease and steatohepatitis. Nat Commun. 2022;13(1):578. doi:10.1038/s41467-022-28138-6
   PubMed Web of Science ®Google Scholar
• Sinclair M, Grossmann M, Gow PJ, Angus PW. Testosterone in men with advanced liver disease: abnormalities and implications. J Gastroenterol Hepatol. 2015;30(2):244–251. doi:10.1111/jgh.12695
   PubMed Web of Science ®Google Scholar
• Bao S, Jin S, Wang C, Tu P, Hu K, Lu J. Androgen receptor suppresses vasculogenic mimicry in hepatocellular carcinoma via circRNA7/miRNA7-5p/VE-cadherin/Notch4 signalling. J Cell Mol Med. 2020;24(23):14110–14120. doi:10.1111/jcmm.16022
   PubMed Web of Science ®Google Scholar
• Ma WL, Hsu CL, Wu MH, et al. Androgen receptor is a new potential therapeutic target for the treatment of hepatocellular carcinoma. Gastroenterology. 2008;135(3):947–55, 955.e1–5. doi:10.1053/j.gastro.2008.05.046
   Web of Science ®Google Scholar
• Ao J, Meng J, Zhu L, et al. Activation of androgen receptor induces ID1 and promotes hepatocellular carcinoma cell migration and invasion. Mol Oncol. 2012;6(5):507–515. doi:10.1016/j.molonc.2012.06.005
   PubMed Web of Science ®Google Scholar
• Gioeli D, Ficarro SB, Kwiek JJ, et al. Androgen receptor phosphorylation. Regulation and identification of the phosphorylation sites. J Biol Chem. 2002;277(32):29304–29314. doi:10.1074/jbc.M204131200
   PubMed Web of Science ®Google Scholar
• Sharma V, Thangaraj K, Jyothy A. A novel insertion-induced frameshift mutation of the androgen receptor gene in a patient with primary amenorrhea. Meta Gene. 2014;2:11–15. doi:10.1016/j.mgene.2013.10.011
   PubMedGoogle Scholar
• Wasmuth EV, Broeck AV, LaClair JR, et al. Allosteric interactions prime androgen receptor dimerization and activation. Molecular Cell. 2022;82(11):2021–2031.e5. doi:10.1016/j.molcel.2022.03.035
   PubMed Web of Science ®Google Scholar
• Feng H, Cheng AS, Tsang DP, et al. Cell cycle-related kinase is a direct androgen receptor-regulated gene that drives β-catenin/T cell factor-dependent hepatocarcinogenesis. J Clin Invest. 2011;121(8):3159–3175. doi:10.1172/jci45967
   PubMed Web of Science ®Google Scholar
• Zhao L, Jin Y, Donahue K, et al. Tissue Repair in the Mouse Liver Following Acute Carbon Tetrachloride Depends on Injury-Induced Wnt/β-Catenin Signaling. Hepatology. 2019;69(6):2623–2635. doi:10.1002/hep.30563
   PubMed Web of Science ®Google Scholar
• Ando A, Hashimoto N, Sakamoto K, et al. Repressive role of stabilized hypoxia inducible factor 1α expression on transforming growth factor β-induced extracellular matrix production in lung cancer cells. Cancer Science. 2019;110(6):1959–1973. doi:10.1111/cas.14027
   PubMed Web of Science ®Google Scholar
• Mandke P, Vasquez KM. Interactions of high mobility group box protein 1 (HMGB1) with nucleic acids: implications in DNA repair and immune responses. DNA Repair. 2019;83:102701. doi:10.1016/j.dnarep.2019.102701
   PubMed Web of Science ®Google Scholar
• Iachettini S, Ciccarone F, Maresca C, et al. The telomeric protein TERF2/TRF2 impairs HMGB1-driven autophagy. Autophagy. 2023;19(5):1479–1490. doi:10.1080/15548627.2022.2138687
   PubMed Web of Science ®Google Scholar
• Yang H, Wang H, Andersson U. Targeting Inflammation Driven by HMGB1. Front Immunol. 2020;11:484. doi:10.3389/fimmu.2020.00484
   PubMed Web of Science ®Google Scholar
• Klune JR, Dhupar R, Cardinal J, Billiar TR, Tsung A. HMGB1: endogenous danger signaling. Mol Med. 2008;14(7–8):476–484. doi:10.2119/2008-00034.Klune
   PubMed Web of Science ®Google Scholar
• Xu X, Piao HN, Aosai F, et al. Arctigenin protects against depression by inhibiting microglial activation and neuroinflammation via HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB pathways. Br J Pharmacol. 2020;177(22):5224–5245. doi:10.1111/bph.15261
   PubMed Web of Science ®Google Scholar
• Liu Y, Chen L, Gao L, et al. LRRK2 deficiency protects the heart against myocardial infarction injury in mice via the P53/HMGB1 pathway. Free Radic Biol Med. 2022;191:119–127. doi:10.1016/j.freeradbiomed.2022.08.035
   PubMed Web of Science ®Google Scholar
• Ren Y, Cao L, Wang L, et al. Autophagic secretion of HMGB1 from cancer-associated fibroblasts promotes metastatic potential of non-small cell lung cancer cells via NFκB signaling. Cell Death Dis. 2021;12(10):858. doi:10.1038/s41419-021-04150-4
   PubMed Web of Science ®Google Scholar
• Huang Q, Liu J, Shi Z, Zhu X. Correlation of MMP-9 and HMGB1 expression with the cognitive function in patients with epilepsy and factors affecting the prognosis. Cell Mol Biol. 2020;66(3):39–47.
   PubMed Web of Science ®Google Scholar
• Zou M, Dong H, Meng X, et al. Store-operated Ca2+ entry plays a role in HMGB1-induced vascular endothelial cell hyperpermeability. PLoS One. 2015;10(4):e0123432. doi:10.1371/journal.pone.0123432
   PubMed Web of Science ®Google Scholar
• Qin QF, Li XJ, Li YS, et al. AMPK-ERK/CARM1 Signaling Pathways Affect Autophagy of Hepatic Cells in Samples of Liver Cancer Patients. Front Oncol. 2019;9:1247. doi:10.3389/fonc.2019.01247
   PubMed Web of Science ®Google Scholar
• Zhang WK, Gu HW, Li XJ, et al. The dark side of “the force” - lipid nanoparticles enhance the oncogenesis of diethylnitrosamine and result in liver cancer in mice. Nanomedicine. 2017;13(2):701–711. doi:10.1016/j.nano.2016.09.017
   PubMed Web of Science ®Google Scholar
• Chen XZ, Zhang WK, Tang HB, et al. The Ethanol Supernatant Extracts of Liushenwan Could Alleviate Nanodiethylnitrosamine-Induced Liver Cancer in Mice. Can J Gastroenterol Hepatol. 2018;2018:6934809. doi:10.1155/2018/6934809
   PubMed Web of Science ®Google Scholar
• Freund HA. Clinical manifestations and studies in parenchymatous hepatitis. Ann Intern Med. 2023;10:1144–1155.
   Google Scholar
• Sheweita SA, El Banna YY, Balbaa M, Abdullah IA, Hassan HE. N-nitrosamines induced infertility and hepatotoxicity in male rabbits. Environ. Toxicol. 2017;32(9):2212–2220. doi:10.1002/tox.22436
   PubMed Web of Science ®Google Scholar
• Bassil N, Alkaade S, Morley JE. The benefits and risks of testosterone replacement therapy: a review. Therapeutics Clin Risk Management. 2009;5(3):427–448. doi:10.2147/tcrm.s3025
   PubMedGoogle Scholar
• Likos E, Bhattarai A, Weyman CM, Shukla GC. The androgen receptor messenger RNA: what do we know? RNA biology. Jan. 2022;19(1):819–828. doi:10.1080/15476286.2022.2084839
   Google Scholar
• Abdel-Hamid NM, Al-Quzweny RM. Prevalence of Hepatocellular Carcinoma in Men and the Contribution of Androgen and its Receptor in Pathogenesis and Therapy. Curr Mol Pharmacol. 2023;16(5):559–563. doi:10.2174/1874467215666221010092825
   PubMed Web of Science ®Google Scholar
• Meng Z, Liu Q, Liu Y, Yang Y, Shao C, Zhang S. Frizzled-3 suppression overcomes multidrug chemoresistance by Wnt/β-catenin signaling pathway inhibition in hepatocellular carcinoma cells. J Chemother. 2023;1–9. doi:10.1080/1120009x.2023.2182573
   Web of Science ®Google Scholar
• Zhang H, Li XX. Significance and mechanism of androgen receptor overexpression and androgen receptor/mechanistic target of rapamycin cross-talk in hepatocellular carcinoma. Hepatology. 2018;67(6):2271–2286. doi:10.1002/hep.29715
   PubMed Web of Science ®Google Scholar
• Xu J, Zheng L, Chen J, et al. Increasing AR by HIF-2α inhibitor (PT-2385) overcomes the side-effects of sorafenib by suppressing hepatocellular carcinoma invasion via alteration of pSTAT3, pAKT and pERK signals. Cell Death Dis. 2017;8(10):e3095. doi:10.1038/cddis.2017.411
   PubMedGoogle Scholar
• Ren H, Ren B, Zhang J, et al. Androgen enhances the activity of ETS-1 and promotes the proliferation of HCC cells. Oncotarget. 2017;8(65):109271–109288. doi:10.18632/oncotarget.22669
   PubMedGoogle Scholar
• Boonyaratanakornkit V, Melvin V, Prendergast P, et al. High-mobility group chromatin proteins 1 and 2 functionally interact with steroid hormone receptors to enhance their DNA binding in vitro and transcriptional activity in mammalian cells. Mol Cell Biol. 1998;18(8):4471–4487. doi:10.1128/mcb.18.8.4471
   PubMed Web of Science ®Google Scholar
• Verrijdt G, Haelens A, Schoenmakers E, Rombauts W, Claessens F. Comparative analysis of the influence of the high-mobility group box 1 protein on DNA binding and transcriptional activation by the androgen, glucocorticoid, progesterone and mineralocorticoid receptors. Biochem J. 2002;361(Pt 1):97–103. doi:10.1042/0264-6021:3610097
   PubMedGoogle Scholar