Resistance to 3-HTMC-Induced Apoptosis Through Activation of PI3K/Akt, MEK/ERK, and p38/COX-2/PGE2Pathways in Human HT-29 and HCT116 Colorectal Cancer Cells
| Autor: | Aline Pinon, Alain Simon, Mona Diab-Assaf, Vincent Sol, Lama Hassan, Youness Limami, Bertrand Liagre, Josiane Semaan, Christelle Pouget, Catherine Fagnère, Benjamin Rioux |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Chemistry Cell Cell Biology Cell cycle Biochemistry 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure Apoptosis Immunology Cancer cell medicine Cancer research Viability assay Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway |
| Zdroj: | Journal of Cellular Biochemistry. 117:2875-2885 |
| ISSN: | 0730-2312 |
| DOI: | 10.1002/jcb.25600 |
| Popis: | Increasing incidence and mortality of colorectal cancer brings the necessity to uncover new possibilities in its prevention and treatment. Chalcones have been identified as interesting compounds having chemopreventive and antitumor properties. In this study, we investigated the effects of the synthetic chalcone derivative 3-hydroxy-3',4,4',5'-tetra-methoxy-chalcone (3-HTMC) on proliferation, cell cycle distribution, apoptosis, and its mechanism of action in human colorectal HT-29 (COX-2 sufficient) and HCT116 (COX-2 deficient) cancer cells. We showed that 3-HTMC decreased cell viability in a dose-dependent manner with a more potent antiproliferative effect on HCT116 than HT-29 cells. Flow cytometric analysis revealed G2 /M cell cycle accumulation in HT-29 cells and significant G2 /M arrest in HCT116 cells with a subsequent apoptosis shown by appearance of Sub-G1 peak. We demonstrated that 3-HTMC treatment on both cell lines induced apoptotic process associated with overexpression of death receptor DR5, activation of caspase-8 and -3, PARP cleavage, and DNA fragmentation. In addition, 3-HTMC induced activation of PI3K/Akt and MEK/ERK principal survival pathways which delay 3-HTMC-induced apoptosis in both cell lines. Furthermore, COX-2 overexpression in HT-29 cells contributes to apoptosis resistance which explains the difference of sensitivity between HT-29 and HCT116 cells to 3-HTMC treatment. Even if resistance mechanisms to apoptosis reduced chalcone antitumoral potential, our results suggest that 3-HTMC may be considered as an interesting compound for colorectal cancer therapy or chemoprevention. J. Cell. Biochem. 117: 2875-2885, 2016. © 2016 Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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