{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T12:14:43Z","timestamp":1782476083384,"version":"3.54.5"},"reference-count":96,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>With an increasing worldwide prevalence, hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver in the world. It is also the primary reason for cancer-related death in the world. The pathogenesis of HCC is complex, such as DNA methylation changes, immune regulatory disorders, cell cycle disorders, chromosomal instability, and so on. Although many studies have been conducted on HCC, the molecular mechanisms of HCC are not completely understood. At present, there is no effective treatment for HCC. Hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) has long been regarded as a toxic gas with the smell of rotten eggs, but recent studies have shown that it is an important gasotransmitter along with carbon monoxide (CO) and nitric oxide (NO). Increasing evidence indicates that H<jats:sub>2<\/jats:sub>S has multiple biological functions, such as anti-inflammation, anti-apoptosis, anti-oxidative stress, and so on. Recently, a lot of evidence has shown that H<jats:sub>2<\/jats:sub>S has a \u201cdouble-edged sword\u201d effect in HCC, but the mechanism is not fully understood. Here, we reviewed the progress on the role and mechanism of H<jats:sub>2<\/jats:sub>S in HCC in recent years, hoping to provide a theoretical reference for future related research.<\/jats:p>","DOI":"10.3389\/fphar.2023.1280308","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T05:03:06Z","timestamp":1697000586000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["The double-edged sword role of hydrogen sulfide in hepatocellular carcinoma"],"prefix":"10.3389","volume":"14","author":[{"given":"Huijie","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodi","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoren","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saadullah","family":"Khattak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honggang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.ygeno.2012.11.009","article-title":"Gene expression alterations in doxorubicin resistant MCF7 breast cancer cell line","volume":"101","author":"AbuHammad","year":"2013","journal-title":"Genomics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"16091","DOI":"10.3390\/ijms232416091","article-title":"Anticancer effects of fucoxanthin through cell cycle arrest, apoptosis induction, angiogenesis inhibition, and autophagy modulation","volume":"23","author":"Ahmed","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"119984","DOI":"10.1016\/j.lfs.2021.119984","article-title":"Crosstalk between miRNA and PI3K\/AKT\/mTOR signaling pathway in cancer","volume":"285","author":"Akbarzadeh","year":"2021","journal-title":"Life Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"383","DOI":"10.3390\/antiox10030383","article-title":"Harnessing the benefits of endogenous hydrogen sulfide to reduce cardiovascular disease","volume":"10","author":"Casin","year":"2021","journal-title":"Antioxidants (Basel)."},{"key":"B5","doi-asserted-by":"publisher","first-page":"8165","DOI":"10.3390\/ijms21218165","article-title":"Recent updates of transarterial chemoembolilzation in hepatocellular carcinoma","volume":"21","author":"Chang","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"5190611","DOI":"10.1155\/2021\/5190611","article-title":"The efficacy of radiotherapy in the treatment of hepatocellular carcinoma with distant organ metastasis","volume":"2021","author":"Chen","year":"2021","journal-title":"J. Oncol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.acr.2020.10.001","article-title":"Hepatocellular carcinoma (HCC): epidemiology, etiology and molecular classification","volume":"149","author":"Chidambaranathan-Reghupaty","year":"2021","journal-title":"Adv. Cancer Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"11601","DOI":"10.1074\/jbc.M808026200","article-title":"H2S biogenesis by human cystathionine gamma-lyase leads to the novel sulfur metabolites lanthionine and homolanthionine and is responsive to the grade of hyperhomocysteinemia","volume":"284","author":"Chiku","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B9","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1111\/bph.14699","article-title":"Hydrogen sulfide and dermatological diseases","volume":"177","author":"Coavoy-S\u00e1nchez","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"109663","DOI":"10.1016\/j.cbi.2021.109663","article-title":"ROS-mediated mitophagy and apoptosis are involved in aluminum-induced femoral impairment in mice","volume":"349","author":"Cui","year":"2021","journal-title":"Chem. Biol. Interact."},{"key":"B11","doi-asserted-by":"publisher","first-page":"280","DOI":"10.3390\/biom12020280","article-title":"Vasorelaxant activity of AP39, a mitochondria-targeted H(2)S donor, on mouse mesenteric artery rings in vitro","volume":"12","author":"da Costa Marques","year":"2022","journal-title":"Biomolecules"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1080\/15548627.2020.1752548","article-title":"Autophagy in the physiological endometrium and cancer","volume":"17","author":"Devis-Jauregui","year":"2021","journal-title":"Autophagy"},{"key":"B13","doi-asserted-by":"publisher","first-page":"105119","DOI":"10.1016\/j.phrs.2020.105119","article-title":"Hydrogen sulfide: an endogenous regulator of the immune system","volume":"161","author":"Dilek","year":"2020","journal-title":"Pharmacol. Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"5282","DOI":"10.3748\/wjg.v23.i29.5282","article-title":"From diagnosis to treatment of hepatocellular carcinoma: an epidemic problem for both developed and developing world","volume":"23","author":"Dimitroulis","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.canlet.2019.04.031","article-title":"A novel hydrogen sulfide-releasing donor, HA-ADT, suppresses the growth of human breast cancer cells through inhibiting the PI3K\/AKT\/mTOR and Ras\/Raf\/MEK\/ERK signaling pathways","volume":"455","author":"Dong","year":"2019","journal-title":"Cancer Lett."},{"key":"B16","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.niox.2017.10.010","article-title":"The mechanism of action and role of hydrogen sulfide in the control of vascular tone","volume":"81","author":"Dong\u00f3","year":"2018","journal-title":"Nitric Oxide"},{"key":"B17","doi-asserted-by":"publisher","first-page":"8456852","DOI":"10.1155\/2023\/8456852","article-title":"A water-soluble hydrogen sulfide donor suppresses the growth of hepatocellular carcinoma via inhibiting the AKT\/GSK-3\u03b2\/\u03b2-Catenin and TGF-\u03b2\/smad2\/3 signaling pathways","volume":"2023","author":"Duan","year":"2023","journal-title":"J. Oncol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"110275","DOI":"10.1016\/j.cellsig.2022.110275","article-title":"Importance of STAT3 signalling in cancer, metastasis and therapeutic interventions","volume":"92","author":"El-Tanani","year":"2022","journal-title":"Cell Signal"},{"key":"B19","doi-asserted-by":"publisher","first-page":"100715","DOI":"10.1016\/j.drup.2020.100715","article-title":"Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance","volume":"53","author":"Erin","year":"2020","journal-title":"Drug Resist Updat"},{"key":"B20","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.phrs.2009.10.008","article-title":"Hydrogen sulfide attenuates epithelial-mesenchymal transition of human alveolar epithelial cells","volume":"61","author":"Fang","year":"2010","journal-title":"Pharmacol. Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"4506","DOI":"10.2174\/0929867330666230126100638","article-title":"Hydrogen sulfide (H(2)S): as a potent modulator and therapeutic prodrug in cancer","volume":"30","author":"Faris","year":"2023","journal-title":"Curr. Med. Chem."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e13111","DOI":"10.1111\/cpr.13111","article-title":"\u03b4-Tocotrienol sensitizes and re-sensitizes ovarian cancer cells to cisplatin via induction of G1 phase cell cycle arrest and ROS\/MAPK-mediated apoptosis","volume":"54","author":"Fontana","year":"2021","journal-title":"Cell Prolif."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1016\/S0140-6736(18)30010-2","article-title":"Hepatocellular carcinoma","volume":"391","author":"Forner","year":"2018","journal-title":"Lancet"},{"key":"B24","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1177\/0960327119877437","article-title":"Hydrogen sulfide modulates IL-6\/STAT3 pathway and inhibits oxidative stress, inflammation, and apoptosis in rat model of methotrexate hepatotoxicity","volume":"39","author":"Fouad","year":"2020","journal-title":"Hum. Exp. Toxicol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"5575","DOI":"10.3390\/cancers13215575","article-title":"Autophagy in cancer therapy-molecular mechanisms and current clinical advances","volume":"13","author":"Ganzleben","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2499","DOI":"10.1038\/sj.onc.1204349","article-title":"Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells","volume":"20","author":"Garcia","year":"2001","journal-title":"Oncogene"},{"key":"B27","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.cnc.2022.04.004","article-title":"Hepatocellular carcinoma","volume":"34","author":"Gilles","year":"2022","journal-title":"Crit. Care Nurs. Clin. North Am."},{"key":"B28","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1161\/HYPERTENSIONAHA.116.08964","article-title":"Impaired hydrogen sulfide-mediated vasodilation contributes to microvascular endothelial dysfunction in hypertensive adults","volume":"69","author":"Greaney","year":"2017","journal-title":"Hypertension"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e0147018","DOI":"10.1371\/journal.pone.0147018","article-title":"Hydrogen sulfide inhibits transforming growth factor-\u03b21-induced EMT via wnt\/catenin pathway","volume":"11","author":"Guo","year":"2016","journal-title":"PLoS One"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1159\/000487578","article-title":"Voruciclib, a potent CDK4\/6 inhibitor, antagonizes ABCB1 and ABCG2-mediated multi-drug resistance in cancer cells","volume":"45","author":"Gupta","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"B31","doi-asserted-by":"publisher","first-page":"3511","DOI":"10.1080\/15548627.2021.1876342","article-title":"Hydrogen sulfide-induced GAPDH sulfhydration disrupts the CCAR2-SIRT1 interaction to initiate autophagy","volume":"17","author":"Iqbal","year":"2021","journal-title":"Autophagy"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1021\/acs.analchem.1c04393","article-title":"Profiling cystathionine \u03b2\/\u03b3-Lyase in complex biosamples using novel activatable fluorogens","volume":"94","author":"Jia","year":"2022","journal-title":"Anal. Chem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1021\/nn405383a","article-title":"Nanographene oxide-hyaluronic acid conjugate for photothermal ablation therapy of skin cancer","volume":"8","author":"Jung","year":"2014","journal-title":"ACS Nano"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1002\/ddr.21954","article-title":"Chrysin promotes angiogenesis in rat hindlimb ischemia: impact on PI3K\/Akt\/mTOR signaling pathway and autophagy","volume":"83","author":"Kamel","year":"2022","journal-title":"Drug Dev. Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"3389","DOI":"10.3390\/molecules27113389","article-title":"Hydrogen sulfide biology and its role in cancer","volume":"27","author":"Khattak","year":"2022","journal-title":"Molecules"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1089\/ars.2009.2919","article-title":"Hydrogen sulfide: from brain to gut","volume":"12","author":"Kimura","year":"2010","journal-title":"Antioxid. Redox Signal"},{"key":"B37","doi-asserted-by":"publisher","first-page":"100670","DOI":"10.1016\/j.drup.2019.100670","article-title":"Phospholipids and cholesterol: inducers of cancer multidrug resistance and therapeutic targets","volume":"49","author":"Kopecka","year":"2020","journal-title":"Drug Resist Updat"},{"key":"B38","doi-asserted-by":"publisher","first-page":"3294","DOI":"10.1007\/s12011-021-02927-4","article-title":"The effects of sodium fluoride (NaF) treatment on the PI3K\/Akt signal pathway in NRK-52e cells","volume":"200","author":"Korkmaz","year":"2022","journal-title":"Biol. Trace Elem. Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"e230421186874","DOI":"10.2174\/1573403X16666201014142446","article-title":"The role of reactive oxygen species, kinases, hydrogen sulfide, and nitric oxide in the regulation of autophagy and their impact on ischemia and reperfusion injury in the heart","volume":"17","author":"Krylatov","year":"2021","journal-title":"Curr. Cardiol. Rev."},{"key":"B40","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1053\/j.gastro.2018.08.065","article-title":"Epidemiology and management of hepatocellular carcinoma","volume":"156","author":"Kulik","year":"2019","journal-title":"Gastroenterology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"2752","DOI":"10.3390\/cells10102752","article-title":"Autophagy and the lysosomal system in cancer","volume":"10","author":"Kumar","year":"2021","journal-title":"Cells"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.3390\/cancers11111646","article-title":"STAT3: an emerging therapeutic target for hepatocellular carcinoma","volume":"11","author":"Lee","year":"2019","journal-title":"Cancers (Basel)"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1111\/liv.15228","article-title":"3-Mercaptopyruvate sulfurtransferase represses tumour progression and predicts prognosis in hepatocellular carcinoma","volume":"42","author":"Li","year":"","journal-title":"Liver Int."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1696","DOI":"10.1111\/liv.15280","article-title":"Response to the clinical significance and prognostic value of 3-mercaptopyruvate sulfurtransferase in hepatocellular carcinoma","volume":"42","author":"Li","year":"","journal-title":"Liver Int."},{"key":"B45","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1007\/s13105-021-00833-w","article-title":"Exosome-derived SNHG16 sponging miR-4500 activates HUVEC angiogenesis by targeting GALNT1 via PI3K\/Akt\/mTOR pathway in hepatocellular carcinoma","volume":"77","author":"Li","year":"2021","journal-title":"J. Physiol. Biochem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"4001","DOI":"10.1080\/21691401.2019.1670670","article-title":"Ribociclib (LEE011) suppresses cell proliferation and induces apoptosis of MDA-MB-231 by inhibiting CDK4\/6-cyclin D-Rb-E2F pathway","volume":"47","author":"Li","year":"2019","journal-title":"Artif. Cells Nanomed Biotechnol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nat. Rev. Dis. Prim."},{"key":"B48","doi-asserted-by":"publisher","first-page":"48","DOI":"10.3389\/fonc.2019.00048","article-title":"Signal transducer and activator of transcription (STATs) proteins in cancer and inflammation: functions and therapeutic implication","volume":"9","author":"Loh","year":"2019","journal-title":"Front. Oncol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.3892\/ijo.2014.2305","article-title":"GYY4137, a hydrogen sulfide (H\u2082S) donor, shows potent anti-hepatocellular carcinoma activity through blocking the STAT3 pathway","volume":"44","author":"Lu","year":"2014","journal-title":"Int. J. Oncol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"2969","DOI":"10.3892\/or.2018.6362","article-title":"Anticancer effect of exogenous hydrogen sulfide in cisplatin-resistant A549\/DDP cells","volume":"39","author":"Ma","year":"2018","journal-title":"Oncol. Rep."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1753","DOI":"10.22038\/IJBMS.2021.56477.12604","article-title":"Combined effect of hydrogen sulfide and mesenchymal stem cells on mitigating liver fibrosis induced by bile duct ligation: role of anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-fibrotic biomarkers","volume":"24","author":"Mohammed","year":"2021","journal-title":"Iran. J. Basic Med. Sci."},{"key":"B52","doi-asserted-by":"publisher","first-page":"5769","DOI":"10.1021\/acs.analchem.6b00087","article-title":"Organelle-targeted H2S probes enable visualization of the subcellular distribution of H2S donors","volume":"88","author":"Montoya","year":"2016","journal-title":"Anal. Chem."},{"key":"B53","doi-asserted-by":"publisher","first-page":"4489","DOI":"10.1080\/15548627.2021.1968608","article-title":"Impairment of ULK1 sulfhydration-mediated lipophagy by SREBF1\/SREBP-1c in hepatic steatosis","volume":"17","author":"Nguyen","year":"","journal-title":"Autophagy"},{"key":"B54","doi-asserted-by":"publisher","first-page":"3820","DOI":"10.1016\/j.molcel.2021.06.003","article-title":"SREBP-1c impairs ULK1 sulfhydration-mediated autophagic flux to promote hepatic steatosis in high-fat-diet-fed mice","volume":"81","author":"Nguyen","year":"","journal-title":"Mol. Cell"},{"key":"B55","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1007\/s10585-018-9903-0","article-title":"The challenge of drug resistance in cancer treatment: a current overview","volume":"35","author":"Nikolaou","year":"2018","journal-title":"Clin. Exp. Metastasis"},{"key":"B56","doi-asserted-by":"publisher","first-page":"109149","DOI":"10.1016\/j.abb.2022.109149","article-title":"Cystathionine beta-Synthase in hypoxia and ischemia\/reperfusion: a current overview","volume":"718","author":"Omorou","year":"2022","journal-title":"Arch. Biochem. Biophys."},{"key":"B57","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1089\/ars.2021.0039","article-title":"Gasping for sulfide: a critical appraisal of hydrogen sulfide in lung disease and accelerated aging","volume":"35","author":"Pacitti","year":"2021","journal-title":"Antioxid. Redox Signal"},{"key":"B58","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.mrfmmm.2014.03.002","article-title":"Hydrogen sulfide (H2S)\/cystathionine \u03b3-lyase (CSE) pathway contributes to the proliferation of hepatoma cells","author":"Pan","year":"2014","journal-title":"Mutat. Res."},{"key":"B59","doi-asserted-by":"publisher","first-page":"113137","DOI":"10.1016\/j.biopha.2022.113137","article-title":"Endogenous and exogenous hydrogen sulfide modulates urothelial bladder carcinoma development in human cell lines","volume":"151","author":"Panza","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"B60","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.bcp.2017.11.014","article-title":"A review of hydrogen sulfide (H(2)S) donors: chemistry and potential therapeutic applications","volume":"149","author":"Powell","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.canlet.2015.07.035","article-title":"Matrine derivative WM130 inhibits hepatocellular carcinoma by suppressing EGFR\/ERK\/MMP-2 and PTEN\/AKT signaling pathways","volume":"368","author":"Qian","year":"2015","journal-title":"Cancer Lett."},{"key":"B62","doi-asserted-by":"publisher","first-page":"166400","DOI":"10.1016\/j.bbadis.2022.166400","article-title":"Role and regulation of autophagy in cancer","volume":"1868","author":"Rakesh","year":"2022","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"B63","doi-asserted-by":"publisher","first-page":"102484","DOI":"10.1016\/j.redox.2022.102484","article-title":"Sulfanegen stimulates 3-mercaptopyruvate sulfurtransferase activity and ameliorates Alzheimer's disease pathology and oxidative stress in vivo","volume":"57","author":"Rao","year":"2022","journal-title":"Redox Biol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"203","DOI":"10.32074\/1591-951X-295","article-title":"Hepatocellular carcinoma: a clinical and pathological overview","volume":"113","author":"Renne","year":"2021","journal-title":"Pathologica"},{"key":"B65","doi-asserted-by":"publisher","first-page":"106311","DOI":"10.1016\/j.phrs.2022.106311","article-title":"STAT3-EMT axis in tumors: modulation of cancer metastasis, stemness and therapy response","volume":"182","author":"Sadrkhanloo","year":"2022","journal-title":"Pharmacol. Res."},{"key":"B66","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1161\/CIRCRESAHA.106.145235","article-title":"Yin Yang-1 inhibits vascular smooth muscle cell growth and intimal thickening by repressing p21WAF1\/Cip1 transcription and p21WAF1\/Cip1-Cdk4-cyclin D1 assembly","volume":"101","author":"Santiago","year":"2007","journal-title":"Circ. Res."},{"key":"B67","doi-asserted-by":"publisher","first-page":"101675","DOI":"10.1016\/j.redox.2020.101675","article-title":"Hydrogen sulfide and DNA repair","volume":"38","author":"Shackelford","year":"","journal-title":"Redox Biol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"437","DOI":"10.3390\/pathophysiology28030028","article-title":"Molecular functions of hydrogen sulfide in cancer","volume":"28","author":"Shackelford","year":"","journal-title":"Pathophysiology"},{"key":"B69","doi-asserted-by":"publisher","first-page":"2699","DOI":"10.1101\/gad.1256504","article-title":"Living with or without cyclins and cyclin-dependent kinases","volume":"18","author":"Sherr","year":"2004","journal-title":"Genes Dev."},{"key":"B70","doi-asserted-by":"publisher","first-page":"5033","DOI":"10.1021\/acsabm.1c00296","article-title":"Transferrin coated d-penicillamine-Au-Cu nanocluster PLGA nanocomposite reverses hypoxia-induced EMT and MDR of triple-negative breast cancers","volume":"4","author":"Shome","year":"2021","journal-title":"ACS Appl. Bio Mater"},{"key":"B71","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.currproblcancer.2017.10.007","article-title":"Hepatocellular carcinoma in the era of immunotherapy","volume":"42","author":"Sim","year":"2018","journal-title":"Curr. Probl. Cancer"},{"key":"B72","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.lfs.2018.10.031","article-title":"Efflux inhibition by H(2)S confers sensitivity to doxorubicin-induced cell death in liver cancer cells","volume":"213","author":"Stokes","year":"2018","journal-title":"Life Sci."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.3390\/biomedicines9111639","article-title":"Targeting the PI3K\/Akt\/mTOR pathway in hepatocellular carcinoma","volume":"9","author":"Sun","year":"2021","journal-title":"Biomedicines"},{"key":"B74","doi-asserted-by":"publisher","first-page":"2502","DOI":"10.1080\/01635581.2020.1836241","article-title":"Fisetin inhibits autophagy in HepG2 cells via PI3K\/Akt\/mTOR and AMPK pathway","volume":"73","author":"Sundarraj","year":"2021","journal-title":"Nutr. Cancer"},{"key":"B75","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.freeradbiomed.2019.07.022","article-title":"S-1-propenylmercaptocysteine protects murine hepatocytes against oxidative stress via persulfidation of Keap1 and activation of Nrf2","volume":"143","author":"Tocmo","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"B76","doi-asserted-by":"publisher","first-page":"264","DOI":"10.7150\/ijbs.38143","article-title":"Hydrogen sulfide plays an important protective role through influencing endoplasmic reticulum stress in diseases","volume":"16","author":"Wang","year":"","journal-title":"Int. J. Biol. Sci."},{"key":"B77","doi-asserted-by":"publisher","first-page":"bio043653","DOI":"10.1242\/bio.043653","article-title":"Exogenous hydrogen sulfide mitigates NLRP3 inflammasome-mediated inflammation through promoting autophagy via the AMPK-mTOR pathway","volume":"8","author":"Wang","year":"2019","journal-title":"Biol. Open"},{"key":"B78","doi-asserted-by":"publisher","first-page":"165","DOI":"10.2147\/OTT.S268570","article-title":"Upregulation of miR-137 expression suppresses tumor growth and progression via interacting with DNMT3a through inhibiting the PTEN\/Akt signaling in HCC","volume":"14","author":"Wang","year":"","journal-title":"Onco Targets Ther."},{"key":"B79","doi-asserted-by":"publisher","first-page":"7848143","DOI":"10.1155\/2022\/7848143","article-title":"Risk factors for brain metastasis of hepatocellular carcinoma","volume":"2022","author":"Wang","year":"","journal-title":"J. Healthc. Eng."},{"key":"B80","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.18632\/aging.203317","article-title":"Puerarin inhibits FUNDC1-mediated mitochondrial autophagy and CSE-induced apoptosis of human bronchial epithelial cells by activating the PI3K\/AKT\/mTOR signaling pathway","volume":"14","author":"Wang","year":"","journal-title":"Aging (Albany NY)"},{"key":"B81","doi-asserted-by":"publisher","first-page":"113487","DOI":"10.1016\/j.ejmech.2021.113487","article-title":"Abnormal saccharides affecting cancer multi-drug resistance (MDR) and the reversal strategies","volume":"220","author":"Wang","year":"","journal-title":"Eur. J. Med. Chem."},{"key":"B82","doi-asserted-by":"publisher","first-page":"e2688","DOI":"10.1038\/cddis.2017.18","article-title":"Hydrogen sulfide promotes autophagy of hepatocellular carcinoma cells through the PI3K\/Akt\/mTOR signaling pathway","volume":"8","author":"Wang","year":"2017","journal-title":"Cell Death Dis."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.3389\/fphar.2020.01152","article-title":"Wogonin induces apoptosis and reverses sunitinib resistance of renal cell carcinoma cells via inhibiting CDK4-RB pathway","volume":"11","author":"Wang","year":"","journal-title":"Front. Pharmacol."},{"key":"B84","doi-asserted-by":"publisher","first-page":"5134","DOI":"10.1038\/s41598-017-05457-z","article-title":"Hydrogen sulfide acts as a double-edged sword in human hepatocellular carcinoma cells through EGFR\/ERK\/MMP-2 and PTEN\/AKT signaling pathways","volume":"7","author":"Wu","year":"2017","journal-title":"Sci. Rep."},{"key":"B85","doi-asserted-by":"publisher","first-page":"6529","DOI":"10.1038\/s41388-020-01450-5","article-title":"High-metastatic cancer cells derived exosomal miR92a-3p promotes epithelial-mesenchymal transition and metastasis of low-metastatic cancer cells by regulating PTEN\/Akt pathway in hepatocellular carcinoma","volume":"39","author":"Yang","year":"2020","journal-title":"Oncogene"},{"key":"B86","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1038\/s41575-019-0186-y","article-title":"A global view of hepatocellular carcinoma: trends, risk, prevention and management","volume":"16","author":"Yang","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1016\/j.cellsig.2012.02.003","article-title":"Sp1 is involved in regulation of cystathionine \u03b3-lyase gene expression and biological function by PI3K\/Akt pathway in human hepatocellular carcinoma cell lines","volume":"24","author":"Yin","year":"2012","journal-title":"Cell Signal"},{"key":"B88","doi-asserted-by":"publisher","first-page":"2672","DOI":"10.3390\/cells10102672","article-title":"Autophagy in tumor immunity and viral-based immunotherapeutic approaches in cancer","volume":"10","author":"Zahedi-Amiri","year":"2021","journal-title":"Cells"},{"key":"B89","doi-asserted-by":"publisher","first-page":"102941","DOI":"10.1016\/j.bioorg.2019.102941","article-title":"Evaluation of thioamides, thiolactams and thioureas as hydrogen sulfide (H(2)S) donors for lowering blood pressure","volume":"88","author":"Zaorska","year":"2019","journal-title":"Bioorg Chem."},{"key":"B90","doi-asserted-by":"publisher","first-page":"323","DOI":"10.3390\/biom10020323","article-title":"Hydrogen sulfide in pharmacotherapy, beyond the hydrogen sulfide-donors","volume":"10","author":"Zaorska","year":"2020","journal-title":"Biomolecules"},{"key":"B91","doi-asserted-by":"publisher","first-page":"608","DOI":"10.3389\/fphar.2017.00608","article-title":"H2S-Induced sulfhydration: biological function and detection methodology","volume":"8","author":"Zhang","year":"2017","journal-title":"Front. Pharmacol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"C720","DOI":"10.1152\/ajpcell.00014.2020","article-title":"3-Mercaptopyruvate sulfurtransferase\/hydrogen sulfide protects cerebral endothelial cells against oxygen-glucose deprivation\/reoxygenation-induced injury via mitoprotection and inhibition of the RhoA\/ROCK pathway","volume":"319","author":"Zhang","year":"2020","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1667\/RR15074.1","article-title":"Blocking endogenous H(2)S signaling attenuated radiation-induced long-term metastasis of residual HepG2 cells through inhibition of EMT","volume":"190","author":"Zhang","year":"2018","journal-title":"Radiat. Res."},{"key":"B94","doi-asserted-by":"publisher","first-page":"646723","DOI":"10.3389\/fcell.2021.646723","article-title":"The role of the signaling pathways involved in the effects of hydrogen sulfide on endoplasmic reticulum stress","volume":"9","author":"Zhao","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B95","doi-asserted-by":"publisher","first-page":"6562","DOI":"10.3892\/ol.2018.8154","article-title":"Exogenous hydrogen sulfide promotes hepatocellular carcinoma cell growth by activating the STAT3-COX-2 signaling pathway","volume":"15","author":"Zhen","year":"2018","journal-title":"Oncol. Lett."},{"key":"B96","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.2147\/JHC.S335425","article-title":"CYP2C8 suppress proliferation, migration, invasion and sorafenib resistance of hepatocellular carcinoma via PI3K\/Akt\/p27(kip1) Axis","volume":"8","author":"Zhou","year":"2021","journal-title":"J. Hepatocell. Carcinoma"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1280308\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T05:03:12Z","timestamp":1697000592000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1280308\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,11]]},"references-count":96,"alternative-id":["10.3389\/fphar.2023.1280308"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1280308","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,11]]},"article-number":"1280308"}}