Additive effect of zinc oxide nanoparticles and isoorientin on apoptosis in human hepatoma cell line

• ZnO Nps could exert dose- and time-dependent cytotoxicity in HepG2 cells.
• The combining treatment resulted in a greater cytotoxicity than single treatment.
• ZnO Nps could additively potentiate ISO to induce apoptosis.
• ZnO Nps were uptaked by endocytic and it enhanced the cellular uptake of ISO.
• No significant injury was found in normal liver cell after the synergistic treatment.

Metal nanomaterial could effectively decrease tumour resistance to anti-cancer drugs. In this paper, we have explored the synergistic effect and mechanisms of zinc oxide nanoparticles (ZnO Nps) and isoorientin (ISO) on cytotoxicity in human hepatoma (HepG2) cells. The results showed that ZnO Nps could exert dose- and time-dependent cytotoxicity in HepG2 cells, and the combining treatment resulted in a greater cytotoxicity than single treatment. ZnO Nps could synergistically potentiate ISO to induce apoptosis through resulting in mitochondrial dysfunction, inhibiting the phosphorylation of Akt and ERK1/2, and enhancing the phosphorylation of JNK and P38. Additionally, ZnO Nps were uptaked by cells through endocytic pathway and it enhanced the cellular uptake of ISO, while no significant injury was found in normal liver cells after the combined treatment. These results suggest that the combination of metal nanoparticle with anti-cancer drugs may provide a promising alternative for novel cancer treatments.