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Synergistic induction of apoptosis in resistant head and neck carcinoma and leukemia by alkoxyamide-based histone deacetylase inhibitors.

Abstract：

:Targeting epigenetic dysregulation has emerged as a valuable therapeutic strategy in cancer treatment. Especially epigenetic combination therapy of histone deacetylase inhibitors (HDACi) with established anti-cancer drugs has provided promising results in preclinical and clinical studies. The structural optimization of alkoxyamide-based class I/IIb inhibitors afforded improved analogs with potent efficacy in cisplatin-resistant head and neck carcinoma cells and bortezomib-resistant leukemia cells. The most promising HDACi showed a superior synergistic cytotoxic activity as compared to vorinostat and class I HDACi in combination with cisplatin, leading to a full reversal of the chemoresistant phenotype in head and neck cancer cell lines, as well in combination with the proteasome inhibitors (bortezomib and carfilzomib) in a panel of leukemic cell lines. Furthermore, the most valuable alkoxyamide-based HDACi exhibited strong ex vivo anticancer efficacy against primary patient samples obtained from different therapy-resistant leukemic entities.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Alves Avelar LA,Schrenk C,Sönnichsen M,Hamacher A,Hansen FK,Schliehe-Diecks J,Borkhardt A,Bhatia S,Kassack MU,Kurz T

doi

10.1016/j.ejmech.2020.113095

subject

Has Abstract

pub_date

2021-02-05 00:00:00

pages

113095

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(20)31067-9

journal_volume

211

pub_type

杂志文章

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