Heat Treatment of Tomato Increases cis-Lycopene Conversion and Enhances Antioxidant Activity in HepG2 Cells

Heat processing of tomato enhances lycopene bioaccessibility by increasing the proportion of cis-isomers; however, the mechanisms linking temperature-dependent isomerization to cellular antioxidant defense remain unclear. In this study, tomato hexane extracts prepared from non-heated, 60 °C-, and 88 °C-treated samples were analyzed to evaluate the effects of temperature on lycopene isomer profiles and cellular redox regulation. HPLC revealed a progressive shift toward cis-lycopene enrichment with increasing temperature, accompanied by enhanced chemical antioxidant capacity. In tert-butyl hydroperoxide (t-BHP)-challenged HepG2 cells, heat-treated extracts significantly improved viability and reduced intracellular reactive oxygen species (ROS). Notably, heme oxygenase-1 (HO-1) induction was attenuated in the 88 °C group relative to the oxidative control group, suggesting a lower level of oxidative or electrophilic stimulation. Redox profiling further showed that heating elevated glutathione reductase (GR) activity, particularly in the 88 °C extract, indicating accelerated regeneration of reduced glutathione (GSH) and compensatory redox adjustment. Collectively, these findings demonstrate that moderate-to-high thermal processing promotes cis-lycopene formation and strengthens both chemical and enzymatic antioxidant defenses, thereby maintaining intracellular redox balance. This study provides mechanistic insight into how heat treatment enhanced lycopene bioactivity in a temperature-dependent manner: while heating at 60 °C preserved cytoprotective effects, treatment at 88 °C further amplified overall antioxidant capacity and enzyme activity.