چاپ صفحه |  صفحه نخست سامانه |  چکیده مقاله |  نویسندگان |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| OBJECTIVE: Many experiments have revealed the anti-tumor activity of spiro-quinazolinone derivatives on different cell types. Exposing KG1-a cells to N-(4- tert- butyl- 4'- oxo- 1'H- spiro [cyclohexane- 1, 2'- quinazoline]- 3'(4'H)- yl)- 4- methyl benzenesulfonamide (4t-CHQ), as an active sub-component of spiro-quinazolinone benzenesulfonamides, the experiment investigated the possible mechanisms that manifest the role of 4t-CHQ in leukemic KG1-a progenitor cells. Mechanistically, the inhibitory effects of 4t-CHQ on KG1-a cells emerges from its madulating function on expression of Bax/Bcl2 and suvinin proteins. METHODS: Cell viability was assessed using MTT assay. The IC50 value of cells was calculated 131.3 µM, after 72h-incubation with 4t-CHQ in ranging from 10 to 150 µM. Apoptotic changes were studied using Acridine Orange/Ethidium Bromide (AO/EB) staining. DNA fragmentation was analyzed by agarose gel electrophoresis method. To evaluate the percentage of apoptotic cells and cell growth dynamic apoptotic features, we performed Annexin V/PI double staining assay and cell cycle analysis by flow cytometry. RESULTS: According to the results, apoptosis induction was initiated by 4t-CHQ in the KG1-a cells (at IC50 value). Cell dynamic analysis revealed that cell cycle at G1 phase was arrested after treatment with 4t-CHQ. Western blotting analysis showed enhancement in the expression ratio of Bax/Bcl-2, while expression of survinin protein decreased in a time-dependent manner in the KG1-a cells. According to docking simulation data, the effectiveness of 4t-CHQ on KG1-a cells, commenced by its reactions with the functional domain of BH3 and Bcl2 and BIR domains of survivin protein. CONCLUSION: These results demonstrate a remarkable role of 4t- CHQ in arresting of lukumia KG1-a stem cells both by induction of opoptosis as well as by down-regulating survivin and Bcl2 proteins. |
| نویسنده | نفر چندم مقاله |
|---|---|
| رضا رهبرقاضی | سوم |
| حجت اله نوزاد چروده | چهارم |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| PPP.pdf | 1398/07/30 | 234980 | دانلود |
| Mahdavi 2018-172-MS 2nd Proof.pdf | 1398/07/30 | 4970260 | دانلود |
