Lycopene and BITC Cooperatively Target Apoptosis, Angiogenesis, and Redox Balance in HepG2 Cells

Hepatocellular carcinoma (HCC) remains a therapeutic challenge due to its resistance to conventional therapies. Dietary phytochemicals like lycopene and benzyl isothiocyanate (BITC) exhibit promising anticancer properties, but their combinatorial effects in HCC are poorly understood. This study investigated the synergistic potential of lycopene and BITC on HepG2 cells through MTT assay, qPCR analysis of apoptotic/cell cycle genes (Bax, Bcl2, p53, Cdk1, cyclin B1), oxidative stress markers (MDA, SOD, CAT, GPx), and angiogenesis (VEGF). The lycopene-BITC combination demonstrated superior cytotoxicity than the individual treatment (IC50 3.21± 0.14 μM and 12.64± 0.58 μM, respectively). Pro-apoptotic effects of lycopene-BITC combination included Bax upregulation (5.82 ± 0.22-fold), p53 overexpression (2.81 ± 0.10-fold) and Bcl2 suppression (0.11 ± 0.01-fold). Cell cycle arrest at G2/M (58.3%) correlated with Cdk1 (0.14 ± 0.01-fold) and cyclin B1 (0.10 ± 0.01-fold) downregulation. The combination also reduced VEGF expression by 88% and MDA levels by 67.2% while enhancing antioxidant enzymes (SOD: 2.84-fold; catalase: 6.27-fold). Lycopene and BITC inhibit HCC progression through multi-mechanistic actions, including apoptosis induction, cell cycle disruption, angiogenesis suppression, and redox balance restoration. These findings support further development of this phytochemical duo as a multi-targeted HCC therapy.