{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T21:38:27Z","timestamp":1768858707921,"version":"3.49.0"},"reference-count":100,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Liver cancer remains a significant global health challenge, with hepatocellular carcinoma (HCC) being the most prevalent form. Despite advancements in treatment, high recurrence rates and the limited efficacy of conventional therapies highlight the need for novel interventions. Cinobufagin (CB), a bufadienolide extracted from the parotid secretion of Bufo gargarizans and B. melanostictus, has emerged as a promising compound with multiple antitumor mechanisms. This comprehensive review assesses the current evidence regarding CB and its containing medicine, cinobufacini, in liver cancer models. Cinobufacini is a traditional Chinese medicine extract, whereas CB refers specifically to one of its active components. The pharmacodynamic actions of CB include induction of apoptosis, DNA damage, inhibition of proliferation and migration, and modulation of key oncogenic pathways such as PI3K\/Akt\/mTOR, Akt\/ERK, and AURKA-mTOR-eIF4E. Additionally, CB disrupts tumor metabolism and induces oxidative stress. Preclinical studies, both in vitro and in vivo, demonstrate significant antitumor efficacy. However, concerns remain regarding CB\u2019s toxicity profile at high doses. This review emphasizes the therapeutic potential of CB in HCC treatment and advocates for further translational research to optimize its clinical applicability, dosage, and safety.<\/jats:p>","DOI":"10.3390\/ph19010158","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T14:35:38Z","timestamp":1768487738000},"page":"158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cinobufagin as a Potential Intervention Against Liver Cancer\u2014A Comprehensive Review"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5990-5849","authenticated-orcid":false,"given":"Nicole Simone","family":"de Lima Coelho","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Mar\u00edlia (FAMEMA), Mar\u00edlia 17519-030, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vict\u00f3ria Dogani","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Mar\u00edlia (FAMEMA), Mar\u00edlia 17519-030, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0518-0795","authenticated-orcid":false,"given":"Ot\u00e1vio Sim\u00f5es","family":"Girotto","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renato C\u00e9sar Moretti","family":"J\u00fanior","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7477-3805","authenticated-orcid":false,"given":"V\u00edtor Engr\u00e1cia","family":"Valenti","sequence":"additional","affiliation":[{"name":"Systematic Reviews and Meta-Analyses Center, School of Philosophy and Sciences, S\u00e3o Paulo State University, Mar\u00edlia 17525-900, SP, Brazil"},{"name":"Laboratory for Systematic Investigations of Diseases, Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4979-115X","authenticated-orcid":false,"given":"Maria Ang\u00e9lica","family":"Miglino","sequence":"additional","affiliation":[{"name":"Graduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00f4nica Duarte","family":"da Silva","sequence":"additional","affiliation":[{"name":"Graduate Program in Anatomy of Domestic and Wild Animals, Faculty of Veterinary Medicine and Animal Science, Universidade de S\u00e3o Paulo (FMVZ\/USP), S\u00e3o Paulo 05508-270, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caio S\u00e9rgio Galina","family":"Spilla","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Luiza Decanini Miranda","family":"de Souza","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5035-876X","authenticated-orcid":false,"given":"Sandra Maria","family":"Barbalho","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"},{"name":"Laboratory for Systematic Investigations of Diseases, Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"},{"name":"Graduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"},{"name":"Department of Biochemistry and Nutrition, School of Food and Technology of Mar\u00edlia (FATEC), Mar\u00edlia 17500-000, SP, 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