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Cell Cycle ; 19(14): 1768-1776, 2020 07.
Article in English | MEDLINE | ID: mdl-32564665

ABSTRACT

HTLV-1 is a human retrovirus responsible for adult T-cell leukemia (ATL) and certain other clinical disorders. The viral Tax oncoprotein plays a central role in HTLV-1 pathogenicity, mainly due to its capacity of inducing the transcriptional activity of various transcriptional factors like NFқB. Eucalyptus camaldulensis (Ec) is considered as a traditional medicinal plant with valuable therapeutic effects. Here we evaluated the activity of its ethanolic leave extract on different Tax activities by testing its influence on Tax-induced activity of NFқB and HTLV-1 LTR in Jurkat cells. Our results showed that Ec inhibited Tax induced activation of NFқB -, SRF- dependent promoters and HTLV-1 LTR. Ec extract has no effect on the binding of Tax to NFқB while it strongly prevented the degradation of IҝBα induced by Tax probably as a result of preventing the link between Tax and IKKγ. In addition, increasing the cellular level of P-TEFb-cyclinT1 significantly reduced the inhibitory effect of Ec on Tax activities, probably by preventing the interaction between Tax and P-TEFb-cyclin T1. The 40%-MeOH fraction of this extract, which is rich with polyphenols, offered the highest inhibitory effect against Tax activities. Further studies are required for the isolation and identification of active component/s in this extract which may be developed in the future as preventive/curing drugs for HTLV-1 related diseases.


Subject(s)
Ethanol/chemistry , Eucalyptus/chemistry , Gene Products, tax , Human T-lymphotropic virus 1/metabolism , Plant Extracts/pharmacology , Plant Leaves/chemistry , Cyclin T/metabolism , Humans , I-kappa B Kinase/metabolism , Inhibitory Concentration 50 , Jurkat Cells , NF-KappaB Inhibitor alpha/metabolism , NF-kappa B/metabolism , Terminal Repeat Sequences/genetics , Transcription Factors/metabolism , Tumor Necrosis Factor-alpha/pharmacology
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