Fantastic Frogs and Where to Use Them: Unveiling the Hidden Cinobufagin’s Promise in Combating Lung Cancer Development and Progression Through a Systematic Review of Preclinical Evidence

• Published in: Cancers Vol. 16; no. 22; p. 3758
• Main Authors: Barbalho, Sandra Maria, Torres Pomini, Karina, Lima, Enzo Pereira de, da Silva Camarinha Oliveira, Jéssica, Boaro, Beatriz Leme, Cressoni Araújo, Adriano, Landgraf Guiguer, Elen, Rici, Rose Eli Grassi, Maria, Durvanei Augusto, Haber, Jesselina Francisco dos Santos, Catharin, Virgínia Maria Cavallari Strozze, Cincotto dos Santos Bueno, Patrícia, Pereira, Eliana de Souza Bastos Mazuqueli, de Alvares Goulart, Ricardo, Laurindo, Lucas Fornari
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 07-11-2024; MDPI
• Subjects: AKT protein; Apoptosis; BAX protein; Bcl-2 protein; Cancer therapies; Caveolin-1; Cell culture; Cell cycle; Cell growth; Cell migration; FOXO1 protein; Inclusion; Kinases; Lung cancer; Lung diseases; Metastasis; Molecular modelling; Mutation; Proteins; Public health; Stat3 protein; Systematic Review; Toxicity; Tumor cell lines
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16223758

Cinobufagin (CB), a bufadienolide, has shown promising potential as an anticancer agent, particularly in combating lung cancer. This systematic review synthesizes preclinical evidence on CB’s effects against lung cancer, focusing on its mechanisms of action, efficacy, and potential clinical implications. We analyzed data from various preclinical studies involving both in vitro cell line models and in vivo animal models. The reviewed studies indicate that CB effectively reduces cell viability, induces apoptosis, and inhibits cell proliferation, migration, and invasion across multiple lung cancer cell lines and xenograft models. Specifically, CB was found to decrease cell viability and increase apoptosis in lung cancer cells by modulating key molecular pathways, including Bcl-2, Bax, cleaved caspases, caveolin-1, FLOT2, Akt, STAT3, and FOXO1. In vivo studies further demonstrated significant inhibition of tumor growth with minimal toxicity. However, limitations include reliance on in vitro models, which may not fully represent in vivo tumor dynamics, and a lack of long-term safety data. The studies also vary in their methodologies and cell line models, which may not accurately encompass all lung cancer subtypes or predict human responses. Despite these limitations, CB’s ability to target specific molecular pathways and its promising results in preclinical models suggest it could be a valuable addition to lung cancer treatment strategies. Our review suggests further clinical trials to validate its efficacy and safety in humans. Future research should explore combination therapies and optimize delivery methods to enhance clinical outcomes.