Escin, a pentacyclic triterpene, chemosensitizes human tumor cells through inhibition of nuclear factor-kappaB signaling pathway.

Molecular Pharmacology
Kuzhuvelil B HarikumarBharat B Aggarwal

Abstract

Agents that can enhance tumor cell apoptosis and inhibit invasion have potential for the treatment of cancer. Here, we report the identification of escin, a pentacyclic triterpenoid from horse chestnut that exhibits antitumor potential against leukemia and multiple myeloma. Whether examined by esterase staining, phosphatidyl-serine staining, DNA breakage, or caspase-mediated poly(ADP-ribose) polymerase cleavage, escin potentiated tumor necrosis factor (TNF)-induced apoptosis but inhibited tumor cell invasion. This correlated with the down-regulation of bcl-2, cellular inhibitor of apoptosis protein-2, cyclin D1, cyclooxygenase-2, intercellular adhesion molecule-1, matrix metalloproteinase-9, and vascular endothelial growth factor, which are all regulated by the activation of the transcription factor NF-kappaB. When examined by electrophoretic mobility shift assay, the triterpenoid suppressed nuclear factor-kappaB (NF-kappaB) activation induced by TNF and other inflammatory agents, and this correlated with the inhibition of IkappaBalpha phosphorylation and degradation, inhibition of IkappaB kinase complex (IKK) activation, suppression of p65 phosphorylation and nuclear translocation, and abrogation of NF-kappaB-dependent reporte...Continue Reading

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Citations

Jan 15, 2014·International Journal of Pediatric Otorhinolaryngology·Chul Ho JangMin Young Kim
Jun 20, 2014·Archives of Biochemistry and Biophysics·Subash C GuptaBharat B Aggarwal
Apr 30, 2014·Journal of Experimental & Clinical Cancer Research : CR·Evandro Luís NieroGláucia Maria Machado-Santelli
Jan 13, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Anna-Maria KatsoriWim Vanden Berghe
Jan 18, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Lenka VarinskáPeter Gál
Dec 22, 2012·International Archives of Allergy and Immunology·Wolfgang SiposPetra Doerfler
Oct 29, 2010·Phytotherapy Research : PTR·M Soledad Vela GurovicPilar Sancho López
Mar 6, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Liping ZhuOscar A Carretero
Jun 10, 2011·Free Radical Research·Bokyung SungBharat B Aggarwal
Mar 28, 2012·Phytotherapy Research : PTR·Gabriela MojžišováJán Richnavský
Dec 24, 2010·Human & Experimental Toxicology·Yuan DuFeng-Hua Fu
Oct 6, 2018·European Journal of Pharmacology·Chen-Li ChengSheau-Yun Yuan

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