Effect of trichostatin A on Burkitt's lymphoma cells: Inhibition of EPS8 activity through Phospho-Erk1/2 pathway.

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Effect of trichostatin A on Burkitt's lymphoma cells: Inhibition of EPS8 activity through Phospho-Erk1/2 pathway.

Biochem Biophys Res Commun. 2018 03 18;497(4):990-996

Authors: Sun P, Zhou X, He Y, Liu H, Wang Y, Chen Y, Li M, He Y, Li G, Li Y

Abstract
Histone deacetylase inhibitors (HDACi) manifest great potential for treatment of Burkitt's lymphoma (BL), an aggressive B-cell lymphoma. Epidermal growth factor receptor pathway substrate 8 (EPS8) is confirmed overexpressed and associated with poor prognosis in solid tumors and leukemia. However, EPS8 expression and the relationship between EPS8 and HDACi on BL remains obscure. Here, we hypothesized that trichostatin A (TSA), a pan-HDACi, could inhibit BL cells by downregulating EPS8. We demonstrated that TSA reduced cell viability, induced apoptosis and cell arrest at G0/G1. Mechanismly, TSA attenuated EPS8 and downstream Phospho-Erk1/2 pathway. Knockdown of EPS8 resulted in a significant reduction in cellular proliferation and suppressed Phospho-Erk1/2 pathway activity, particularly when combined with TSA. Conversely, overexpression of EPS8 rescued this phenomenon. Then we showed that the combination of TSA and Epirubicin had a more significant effect when compared with TSA or Epirubicin alone. Finally, knockdown of EPS8 and TSA had a synergistic suppression effect on BALB/c nude mice. In conclusion, this study reveals that TSA affects BL cells by suppressing Phospho-Erk1/2 pathway through downregulating EPS8.

PMID: 29462617 [PubMed - indexed for MEDLINE]

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