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Pro-apoptotic effect of the novel benzylidene derivative MHY695 in human colon cancer cells.
| Content Provider | Europe PMC |
|---|---|
| Author | Heo, Gwangbeom Kang, Dongwan Park, Chaeun Kim, Su Jin Choo, Jieun Lee, Yunna Yoo, Jin-Wook Jung, Yunjin Lee, Jaewon Kim, Nam Deuk Chung, Hae Young Moon, Hyung Ryong Im, Eunok |
| Copyright Year | 2019 |
| Abstract | The induction of apoptosis is a useful strategy in anti-cancer research. Various Moon Hyung Yang (MHY) compounds have been developed as novel anti-cancer drug candidates; in the present study, the pro-apoptotic effects of (Z)-5-(3-ethoxy-4- hydroxybenzylidene)-2-thioxothiazolidin-4-one (MHY695) on HCT116 human colon cancer cells were assessed. MTT assays were performed to investigate the dose-dependent cytotoxic effects of MHY695 on HCT116 cells. Immunofluorescence staining and flow cytometry analyses were performed to identify apoptotic cell death, and western blot analysis was used to investigate the apoptotic-signaling pathways. A mouse xenograft model was also used to determine the effects of MHY695 in vivo. MHY695 decreased the viability of HCT116 cells and induced apoptotic cytotoxicity. The apoptotic mechanisms induced by MHY695 involved the dephosphorylation of Bcl-2-associated agonist of cell death protein following protein kinase B inactivation, induced myeloid leukaemia cell differentiation protein and BH3-interacting domain death agonist truncation, caspase-3 and −9 activation and poly (ADP-ribose) polymerase cleavage. In addition, MHY695 significantly suppressed tumor growth in the mouse xenograft model, compared with the vehicle control. Notably, MHY695 exhibited potent anti-cancer effects in four different types of human colon cancer cell line, including Caco-2, DLD-1, HT-29 and HCT116. Additionally, MHY695 showed reduced cytotoxicity in NCM460, normal colonic epithelial cells. Furthermore, MHY-induced cytotoxicity in colon cancer cells was independent of the tumor suppressor protein p53. Collectively, these observations suggested that MHY695 may be a novel drug for the treatment of colon cancer. |
| ISSN | 17921074 |
| Journal | Oncology Letters |
| Volume Number | 18 |
| PubMed Central reference number | PMC6704326 |
| Issue Number | 3 |
| PubMed reference number | 31452803 |
| e-ISSN | 17921082 |
| DOI | 10.3892/ol.2019.10664 |
| Language | English |
| Publisher | D.A. Spandidos |
| Publisher Date | 2019-07-25 |
| Access Restriction | Open |
| Rights License | This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Copyright: © Heo et al. |
| Subject Keyword | colon cancer apoptosis caspase poly(ADP-ribose) polymerase p53 |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology |
