Escin, a pentacyclic triterpene, chemosensitizes human tumor cells through inhibition of nuclear factor-kappaB signaling pathway
Authors: Bokyung Sung
Bharat B Aggarwal
Manoj K Pandey
Sunil Krishnan
Sushovan Guha
Kuzhuvelil B Harikumar
Journal: Molecular Pharmacology (2010)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: tumor cell apoptosis; tumor cell invasion; escin; pentacyclic triterpenoid; leukemia
Affiliations: Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

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 reporter activity. Overall, our results demonstrate that escin inhibits activation of NF-kappaB through inhibition of IKK, leading to down-regulation of NF-kappaB-regulated cell survival and metastatic gene products and thus resulting in sensitization of cells to cytokines and chemotherapeutic agents. 

Retracted: No

PubPeer comments:
 Brought to my attention by a reader. An SEM panel in Figure 1 of this paper looks similar to an SEM panel in Figure 1 of another paper by the same group, i.e. Shichang Zhao et al., Biomaterials (2015), doi: 10.1016 j.biomaterials.2015.02.112 Shown with green boxes. The panels appear to show different materials and immersion days.  , 
 Figures 8 of both papers also appear to share some panels. Shown with boxes of the same color.  , 
 Dear Dr. Eliabeth M Bik: Thank you for transferring the comment from a reader which he she pointed out that an SEM panel in Figure 1 (e) in Materials Science and Engineering C 60 (2016) 437-445 was similar to another SEM panel in Figure 1 (c) in Biomaterials 53 (2015) 379-391. After checking the original images carefully, we found that we did make several big mistakes: 1) put a wrong SEM panel to Figure 1 (e) in the former journal; 2) misused the images (Control-0-day, SiG-9-day and BG-9-day) of full-thickness skin defects in Figure 8; 3) shared the wrong micro-fil control image ((a)-Control) in Figure 9. We are terribly sorry to all readers and the journal for our carelessly selecting the wrong SEM panel and the wrong pictures to be published by opening wrong data folders during Figure 8 preparation. All the experiment published in the two journals have been done by the same research group and written by different first authors of the papers. Unfortunately, these first authors were lack of full communications, and some of the corresponding authors unable browse the manuscript carefully. We sincerely apologize for misleading readers from these mistakes. For correcting these mistakes, we try using the right SEM panel and right pictures to substitute the wrong ones to Figure 1, Figure 8 and Figure 9 respectively in Materials Science and Engineering C 60 (2016) 437-445. We will appreciate it if the readers and the journal forgive our mistakes. The right SEM panel and right pictures are attached. Let me know if there are any questions about the corrected manuscript. Thank you very much for your helps! Attachements: Wrong figure1  Corrected Figure 1  Wrong figure 8  Corrected Figure 8  Wrong figure 9  Corrected Figure 9  The pictures circled with red line are substituted by the respective ones. , 
 3 panels look similar, 2 panels in this paper, 1 panel in another paper published by the same group i e Shichang Zhao et al. Biomaterals (2015) doi:10.1016 j.biomaterials.2015.02.112. Which one is correct? shown with green boxes below  , 
 Dear Dr. Ocyptamus Luctuosus: Many thanks for your comments on two panels (Control and SiG) of Figure 10 (a) in Materials Science and Engineering C 60 (2016) 437-445, which looked similar to the Control panel of Figure 9 (A) in Biomaterials 53 (2015) 379-391. Certainly, the Control panel in the later paper is correct. However, we have already re-put a new Control panel in the former paper (seeing my response in #3 Nai Zhou commented). In the previous response, we did not find the mistake of the SiG panel. Here, we also re-put a new SiG panel to substitute the one in Figure 10 (a), since we have got lots of original pictures of animal experiments. We will immediately contact the journal editor to request these changes. Thank you very much for checking our paper carefully and putting forward to beneficial suggestions. Attachments: Wrong Figure10  Corrected Figure10  The pictures circled with red line are substituted by the respective ones. ,