Targeting Chemical-induced Hepatocellular Carcinoma: Ameliorative Potential of Natural Compounds with Focus on Beta-carbolines.

INTRODUCTION

Hepatocellular carcinoma (HCC), the predominant form of primary liver malignancy, remains a major global health concern owing to its aggressive progression, limited therapeutic efficacy, and high fatality rate. A significant proportion of HCC arises from chronic exposure to chemical carcinogens, which trigger hepatocarcinogenesis through oxidative stress, DNA damage, and dysregulation of signalling networks. Natural compounds, particularly beta-carboline alkaloids, are emerging as safer, multi-targeted candidates with promising hepatoprotective and anticancer potential. This review has critically evaluated chemical-induced hepatocarcinogenesis and the therapeutic relevance of beta-carbolines in HCC.

METHODS

A systematic literature survey was conducted using PubMed, Scopus, and Web of Science databases, emphasizing studies on chemical-induced HCC, natural hepatoprotective compounds, and beta-carboline derivatives. Mechanistic, pharmacological, and preclinical data were extracted and analyzed.

RESULTS

Carcinogens, such as diethylnitrosamine (DEN), aflatoxin B1, and carbon tetrachloride (CCl4), promote HCC by inducing oxidative stress, genotoxicity, and perturbations in signalling cascades, including PI3K/AKT, Wnt/β-catenin, and NF-κB. Beta-carbolines display antioxidant, pro-apoptotic, anti-inflammatory, and anti-metastatic activities, with evidence of direct modulation of oncogenic pathways and tumor microenvironment.

DISCUSSION: The accumulating evidence highlights beta-carbolines as versatile natural agents with multi-faceted mechanisms against chemical-induced hepatocarcinogenesis. Nonetheless, gaps remain in understanding their pharmacokinetics, bioavailability, and long-term safety. Preclinical data are encouraging, but translational studies and clinical validations are limited, underscoring the need for further research.

CONCLUSION

Beta-carboline alkaloids hold significant promise as therapeutic candidates for chemical- induced HCC. Addressing challenges related to safety, bioavailability, and clinical applicability can prove to be crucial for their future development.