Epigallocatechin-3-gallate Induced HepG2 Cells Apoptosis through ROSmediated AKT /JNK and p53 Signaling Pathway

Abstract

Background: Hepatocarcinoma is the third leading cause of cancer-related deaths around the world. Recently, some studies have reported that Epigallocatechin-3-gallate (EGCG) may have the potential for anti-cancer. However, the affection and putative mechanisms of cytotoxicity induced by EGCG in HepG2 cells remain unknown. Based on the above, the present study evaluated the effect of EGCG on the cytotoxic and anti-cancer mechanisms on HepG2 cells. Methods: The effect of EGCG on the apoptosis of Hep-G2 cells and its mechanism were studied by cell counting kit-8, mitochondrial membrane potential assay with JC-1, Annexin V-FITC apoptosis detection, cell cycle, and apoptosis analysis, one step TUNEL apoptosis assay, caspase 3 activity assay, caspase 9 activity Assay, Reactive Oxygen Species assay, and Western blot. Results: EGCG-induced HepG2 cell apoptosis was confirmed by accumulation of the sub-G1 cells population, translocation of phosphatidylserine, depletion of mitochondrial membrane potential, DNA fragmentation, caspase-3 activation, caspase-9 activation, and poly (ADP-ribose) polymerase cleavage. Furthermore, EGCG enhanced cytotoxic effects on HepG2 cells and triggered intracellular reactive oxygen species; the signaling pathways of AKT, JNK, and p53 were activated to advance cell apoptosis. Conclusion: The results reveal that EGCG may provide useful information on EGCG-induced HepG2 cell apoptosis and be an appropriate candidate for cancer chemotherapy.

Epigallocatechin-3-Gallate Therapeutic Potential in Cancer: Mechanism of Action and Clinical Implications

“…It was shown that a prolonged activation of ERK induced cell apoptosis [ 170 ]. Moreover, when EGCG was applied to a hepatocarcinoma cell line (HepG2), its proapoptotic activity was stimulated by the JNK pathway [ 190 ]. However, in a study on human bladder cancer cells (T24), a 30 min pretreatment with EGCG before the application of IL-1β caused the suppression of both the ERK1/2 and JNK pathways by silencing their transcriptional activity, while EGCG, in a concentration range of 0–50 μM, did not affect the T24 cells’ viability [ 191 ].…”