@article {Harikumarmol.109.062760, author = {Kuzhuvelil B. Harikumar and Bokyung Sung and Manoj K. Pandey and Sushovan Guha and Sunil Krishnan and Bharat B. Aggarwal}, title = {Escin, a Pentacyclic Triterpene, Chemosensitizes Human Tumor Cells through Inhibition of NF-κB Signaling Pathway}, elocation-id = {mol.109.062760}, year = {2010}, doi = {10.1124/mol.109.062760}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Agents that can enhance tumor cell apoptosis and inhibit invasion have potential for 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 PARP cleavage, escin potentiated TNF-induced apoptosis but inhibited tumor cell invasion. This correlated with the down-regulation of bcl-2, IAP2, cyclin D1, COX2, ICAM-1, MMP-9 and VEGF, all regulated by the activation of the transcription factor NF-κB. When examined by electrophoretic mobility shift assay, the triterpenoid suppressed NF-κB activation induced by TNF and other inflammatory agents and this correlated with inhibition of IκBα phosphorylation and degradation, inhibition of IKK activation, suppression of p65 phosphorylation and nuclear translocation and abrogation of NF-κB-dependent reporter activity. Overall our results demonstrate that escin inhibits activation of NF-κB through inhibition of IKK, leading to downregulation of NF-κB-regulated cell survival and metastatic gene products and thus resulting in sensitization of cells to cytokines and chemotherapeutic agents.The American Society for Pharmacology and Experimental Therapeutics}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/early/2010/01/26/mol.109.062760}, eprint = {https://molpharm.aspetjournals.org/content/early/2010/01/26/mol.109.062760.full.pdf}, journal = {Molecular Pharmacology} }