Plant-derived natural products against hepatocellular carcinoma: chemical diversity, mechanisms of action, and organ-based classification

Abstract

Liver cancer, particularly hepatocellular carcinoma (HCC), remains a major global health burden due to late diagnosis, limited therapeutic options, and frequent resistance to drugs such as sorafenib, regorafenib, and lenvatinib. Natural products continue to attract attention as a rich source of structurally diverse anticancer candidates. Plant-derived secondary metabolites, including terpenoids, flavonoids, alkaloids, and phenolics, have shown activity against HCC, yet their organisation by plant organ and mechanism of action remains insufficiently addressed. In this review, anti-HCC natural products reported over the past four decades were collected from the Dictionary of Natural Products, PubMed, and Google Scholar. More than 116 compounds were classified by plant sources, including leaves, fruits, seeds, flowers, bark, and subterranean organs. These compounds mainly act by inhibiting proliferation, inducing apoptosis, modulating the cell cycle, suppressing telomerase activity, and regulating key signalling pathways in HCC cell lines, supporting natural products as valuable leads for anti-HCC drug discovery.