Molecular targets and therapeutic implications of curcumin in hepatocellular carcinoma: a comprehensive literature review.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with Limited treatment options and poor outcomes in advanced stages. Curcumin, a bioactive compound derived from Curcuma longa, has drawn significant attention for its anticancer, anti-inflammatory, antioxidant, and immunomodulatory properties. This systematic review evaluated 26 studies published between 2020 and 2025-including in vitro, in vivo, and one clinical investigation-to examine the molecular mechanisms and therapeutic potential of curcumin and its nanoformulations in HCC. Curcumin was found to modulate multiple signaling pathways such as PI3K/AKT/mTOR, JAK2/STAT3, MAPK, and Wnt/β-catenin, leading to enhanced apoptosis, reduced cell proliferation, suppression of angiogenesis, and immune system modulation. Additional findings highlighted its role in reversing drug resistance and promoting ferroptosis through ACSL4 upregulation. Nanoformulated curcumin-delivered via liposomes, micelles, bilosomes, and other carriers-demonstrated improved bioavailability, stability, and tumor-targeting capacity, enhancing therapeutic efficacy in preclinical models. However, the translation of these promising preclinical effects into clinical practice remains limited, with only a single human study available. While curcumin shows potential as a supportive or adjunctive agent in HCC therapy, further well-designed clinical trials are essential to validate its efficacy and optimize formulation strategies for patient use.