β-carotene isolated from the marine red alga, Gracillaria sp. potently attenuates the growth of human hepatocellular carcinoma (HepG2) cells by modulating multiple molecular pathways

[Display omitted] •Beta-carotene at low concentrations effectively inhibits the growth of HepG2 cells.•Its inhibitory effect is linked with altered cell survival, redox and apoptosis signals.•Dietary levels of β-carotene might be more advantageous in preventing liver cancer. There remains a remarkable controversy on the anti-cancer stand of β-carotene specifically when high concentrations are used. This study aimed to examine the growth inhibitory effect of the lower concentrations of β-carotene in HepG2 cells. Beta-carotene purified from Gracillaria sp. inhibited viability of HepG2 cells in a concentration-dependent manner. This growth inhibitory effect was well correlated with increased apoptotic cell death. Apoptosis induction by β-carotene was associated with increased caspase-3 activity and reduced mitochondrial membrane potential. Western blot analysis showed a significant decrease in the expression of Bcl-2, PARP, and NF-kB protein, and an increase in the protein expression of Bax. Beta-carotene also blocked the activation of intracellular growth signaling proteins, Akt and ERK1/2. Further, it down-regulated the expression of endogenous antioxidant enzymes, SOD-2 and HO-1, and its transactivation factor, Nrf-2. The current study emphasizes the role of β-carotene as an effective inhibitor of the growth of hepatocarcinoma cell.