The Effect of Caffeine and chk2 Inhibitor on Doxorubicin-Induced Cellular Senescence in MCF-7 Cells
Autor: | F. Mir Mohammadrezaei, A. Fayyaz Movaghar, Mehdi Gharghabi |
---|---|
Rok vydání: | 2016 |
Předmět: |
0106 biological sciences
Senescence Cyclin-Dependent Kinase Inhibitor p21 animal structures Pharmacology Biology environment and public health 010603 evolutionary biology 01 natural sciences chemistry.chemical_compound Caffeine Drug Discovery polycyclic compounds medicine Humans Doxorubicin Protein Kinase Inhibitors Sensitization Cellular Senescence Cell Proliferation 010405 organic chemistry Cell growth General Medicine beta-Galactosidase 0104 chemical sciences enzymes and coenzymes (carbohydrates) Checkpoint Kinase 2 medicine.anatomical_structure chemistry MCF-7 Cancer cell MCF-7 Cells biological phenomena cell phenomena and immunity Cell aging medicine.drug |
Zdroj: | Drug research. 66(9) |
ISSN: | 2194-9387 |
Popis: | Senescence is cellular growth arrest. Induction of senescence can be considered as an alternative approach for treating cancer cells being resistance to anti-cancer drugs. We investigated the effect of caffeine and chk2 inhibitor on doxorubicin induced senescence in MCF-7 cells. Caffeine and chk2 inhibitor were used in combination with doxorubicin. Cellular senescence was assessed by β-galactosidase assay. P21 expression was determined using immunoblotting. Cell proliferation was evaluated using prestoblue assay. Results revealed that doxorubicin induced senescence and increased p21 expression in MCF-7 cells. However, co-treatment of chk2 inhibitor and caffeine with doxorubicin could not augment doxorubicin-induced senescence. Moreover, p21 expression was decreased in combination studies compared to doxorubicin group. Our results indicate that caffeine, chk2 inhibitor and combination of chk2 inhibitor, caffeine and doxorubicin could not increase sensitivity of the cells to doxorubicin-induced senescence. Our findings demonstrate that low-dose doxorubicin induced senescence via the activation of ATM, -chk2, and -p21 pathways, while inhibition of ATM and chk2 cannot consider as a new target for sensitization of MCF-7 cells to doxorubicin. Thus, chk2 inhibitor and caffeine might not serve as desirable agents being capable to restore chemo sensitivity in doxorubicin-resistant breast tumors. |
Databáze: | OpenAIRE |
Externí odkaz: |