التفاصيل البيبلوغرافية
العنوان:
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
المؤلفون:
Aline Pinon , Alain Simon , Mona Diab-Assaf , Vincent Sol , Lama Hassan , Youness Limami , Bertrand Liagre , Josiane Semaan , Christelle Pouget , Catherine Fagnère , Benjamin Rioux
المصدر:
Journal of Cellular Biochemistry . 117:2875-2885
بيانات النشر:
Wiley, 2016.
سنة النشر:
2016
مصطلحات موضوعية:
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
الوصف:
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.
تدمد:
0730-2312
DOI:
10.1002/jcb.25600
URL الوصول:
https://explore.openaire.eu/search/publication?articleId=doi_________::a14165504299237bf6b95388d36c4146 https://doi.org/10.1002/jcb.25600
Rights:
CLOSED
رقم الانضمام:
edsair.doi...........a14165504299237bf6b95388d36c4146
قاعدة البيانات:
OpenAIRE