An Active Compound from the Pyrazine Family Induces Apoptosis by Targeting the Bax/Bcl2 and Survivin Expression in Chronic Myeloid Leukemia K562 Cells
- Авторлар: Rostampour S.1, Eslami F.1, Babaei E.1, Mostafavi H.2, Mahdavi M.1
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Мекемелер:
- Department of Biology, Faculty of Natural Science, University of Tabriz
- Department of Organic Chemistry, Faculty of Chemistry, University of Tabriz
- Шығарылым: Том 24, № 3 (2024)
- Беттер: 203-212
- Бөлім: Oncology
- URL: https://snv63.ru/1871-5206/article/view/644121
- DOI: https://doi.org/10.2174/0118715206272359231121105713
- ID: 644121
Дәйексөз келтіру
Толық мәтін
Аннотация
Background:It has been established that pyrazine derivatives, which have widespread bioactivities, can effectively treat cancer.
Objectives:In this study, we investigated the effects of 2-methoxy-5-(oxiran-2-ylmethyl) phenyl pyrazine-2- carboxylate (2-mOPP), a new pyrazine derivative, on proliferation, viability, and apoptosis induction in human leukemia K562 cells.
Methods::For this purpose, the K562 cells were treated with various concentrations (20-120 µM) of the 2-mOPP for 24-72 hours. Cell viability was determined by MTT growth inhibition assay. Apoptotic activity of 2-mOPP was investigated morphologically by Hoechst staining, cell surface expression assay of phosphatidylserine by Annexin-V/PI technique, as well as DNA fragmentation assay. The effect of 2-mOPP on the K562 cell cycle was studied by flow cytometry. To determine the impact of 2-mOPP on the expression of intrinsic apoptosis-related genes, Bcl2 (anti-apoptotic), Bax (pro-apoptotic), and Survivin genes expression levels were evaluated before and after treatment with 2-mOPP through Real-Time PCR analysis.
Results::The results revealed that 2-mOPP inhibited viability with IC50 of 25µM in 72 h. Morphological changes assessment by fluorescence microscopy, Annexin V/PI double staining by flow cytometry, and DNA ladders formation upon cell treatment with the 2-mOPP showed that this compound induces apoptosis at IC50 value. Cell cycle arrest was observed in the G0/G1 phase, and the sub-G1 cell population (the sign of apoptosis) increased in a time-dependent manner. Low expression levels of Bcl2 and Survivin in K562 cells were observed 24-72 h after treatment. Along with the down-regulation of Survivin and Bcl2, the expression of Bax was increased after treatment with 2-mOPP.
Conclusion:These findings demonstrate that the new pyrazine derivative plays a crucial role in blocking the proliferation of the leukemic cells by inducing cell cycle arrest and apoptosis.
Авторлар туралы
Saeedeh Rostampour
Department of Biology, Faculty of Natural Science, University of Tabriz
Email: info@benthamscience.net
Farhad Eslami
Department of Biology, Faculty of Natural Science, University of Tabriz
Email: info@benthamscience.net
Esmaeil Babaei
Department of Biology, Faculty of Natural Science, University of Tabriz
Email: info@benthamscience.net
Hossein Mostafavi
Department of Organic Chemistry, Faculty of Chemistry, University of Tabriz
Email: info@benthamscience.net
Majid Mahdavi
Department of Biology, Faculty of Natural Science, University of Tabriz
Хат алмасуға жауапты Автор.
Email: info@benthamscience.net
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