The oxidation of (−)-epigallocatechin-3-gallate inhibits T-cell acute lymphoblastic leukemia cell line HPB-ALL via the regulation of Notch1 expression

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy, and commonly associated with activating mutations in the Notch1 pathway. (−)-Epigallocatechin-3-gallate (EGCG) is the most abundant and active catechin and has been shown to regulate Notch signaling. Taking into account the highly oxidizable and unstable of EGCG, we proposed that EGCG oxides may have greater potential to regulate Notch signaling than EGCG. In this study, we isolated and identified EGCG oxides (compound 2–4), using a chemical oxidation strategy, and evaluated for cytotoxicity against T-cell acute lymphoblastic leukemia cell line (HPB-ALL) by using the MTS assay. We found compound 3 significantly induced cell proliferation inhibition (38.3858 ± 1.67106 μM), cell apoptosis and cell cycle arrest in a dose-dependent manner. Remarkably, compound 3 inhibited expression of Notch1 compared with EGCG in HPB-ALL cells. Meanwhile, we found that compound 3 significantly inhibited c-Myc and Hes1, which are downstream target genes of Notch1. The findings demonstrate for the first time that an oxidation product of EGCG (compound 3) inhibits T-cell acute lymphoblastic leukemia cell line (HPB-ALL) and is a promising agent for cancer therapy deserving further research.