# Cinobufagin as a Potential Intervention Against Liver Cancer—A Comprehensive Review

**Authors:** Nicole Simone de Lima Coelho, Victória Dogani Rodrigues, Otávio Simões Girotto, Renato César Moretti Júnior, Vítor Engrácia Valenti, Maria Angélica Miglino, Mônica Duarte da Silva, Caio Sérgio Galina Spilla, Ana Luiza Decanini Miranda de Souza, Sandra Maria Barbalho, Lucas Fornari Laurindo

PMC · DOI: 10.3390/ph19010158 · 2026-01-15

## TL;DR

Cinobufagin, a compound from toad venom, shows promise as a treatment for liver cancer by targeting multiple cancer pathways and inducing cell death.

## Contribution

This paper provides a comprehensive review of Cinobufagin's antitumor mechanisms and preclinical efficacy in liver cancer.

## Key findings

- Cinobufagin induces apoptosis and DNA damage in liver cancer cells.
- It inhibits cancer cell proliferation and migration by modulating key oncogenic pathways.
- Preclinical studies show significant antitumor effects, though toxicity at high doses remains a concern.

## Abstract

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’s 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.

## Linked entities

- **Proteins:** PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), AKT1 (AKT serine/threonine kinase 1), MTOR (mechanistic target of rapamycin kinase), EPHB2 (EPH receptor B2), AURKA (aurora kinase A), EIF4E (eukaryotic translation initiation factor 4E)
- **Chemicals:** Cinobufagin (PubChem CID 11969542)
- **Diseases:** Liver cancer (MONDO:0002691), Hepatocellular carcinoma (MONDO:0007256), HCC (MONDO:0007256)
- **Species:** Bufo gargarizans (taxon 30331)

## Full-text entities

- **Diseases:** toxicity (MESH:D064420), HCC (MESH:D006528), tumor (MESH:D009369)
- **Chemicals:** bufadienolide (MESH:C087925), CB (MESH:C002471), Chinese medicine (-)
- **Species:** Duttaphrynus melanostictus (Asian common toad, species) [taxon 30335], Bufo gargarizans (Asiatic toad, species) [taxon 30331]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12845374/full.md

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Source: https://tomesphere.com/paper/PMC12845374