A mix of natural extracts of turmeric, ginger, and licorice root induce HepG2 cancer cell death through paraptosis.

This study investigated the effects of single, dual, and triple combinations of turmeric (TE), ginger (GE), and licorice root (LE) extracts on caspase expression, combination interactions, and apoptosis in HepG2 cells. Caspase-3 and caspase-9 expression significantly increased in all treatment groups compared with the control (p < 0.001), with the highest levels observed in the LE (300 μg/mL) group. Caspase-8 and endoplasmic reticulum (ER) stress markers, including Binding immunoglobulin protein (BiP) and C/EBP homologous protein (CHOP), were most elevated in the triple combination (TE + GE + LE) (p < 0.001). Combination analyses indicated synergistic effects at certain doses, while antagonistic interactions were observed in some GE + LE dual combinations. Single treatments of TE (75 μg/mL) and GE (80 μg/mL) produced the strongest apoptotic response, whereas LE showed a weaker effect. In contrast, binary combinations reduced apoptotic cell percentages, and in the triple combination, apoptosis levels decreased to near-control values (p < 0.001). Despite reduced apoptosis, caspase activation and ER stress markers increased in the triple combination, indicating that cell death is not solely dependent on apoptosis. These findings suggest that multiple regulated pathways, including ER stress-related mechanisms, may contribute to cell death depending on dose and combination type, highlighting the complexity of interactions among these natural extracts in cancer cell models.