An Active Compound from the Pyrazine Family Induces Apoptosis by Targeting the Bax/Bcl2 and Survivin Expression in Chronic Myeloid Leukemia K562 Cells
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
|---|---|
| Enthalten in: |
Anti-cancer agents in medicinal chemistry - 24(2024), 3 vom: 29., Seite 203-212 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Rostampour, Saeedeh [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
2-mOPP |
|---|
| Anmerkungen: |
Date Completed 18.04.2024 Date Revised 18.04.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.2174/0118715206272359231121105713 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM365291293 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM365291293 | ||
| 003 | DE-627 | ||
| 005 | 20240418232357.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.2174/0118715206272359231121105713 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1379.xml |
| 035 | |a (DE-627)NLM365291293 | ||
| 035 | |a (NLM)38038011 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Rostampour, Saeedeh |e verfasserin |4 aut | |
| 245 | 1 | 3 | |a An Active Compound from the Pyrazine Family Induces Apoptosis by Targeting the Bax/Bcl2 and Survivin Expression in Chronic Myeloid Leukemia K562 Cells |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 18.04.2024 | ||
| 500 | |a Date Revised 18.04.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a BACKGROUND: It has been established that pyrazine derivatives, which have widespread bioactivities, can effectively treat cancer | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a 2-mOPP | |
| 650 | 4 | |a Bcl2 | |
| 650 | 4 | |a K562 cell. | |
| 650 | 4 | |a apoptosis | |
| 650 | 4 | |a leukemia | |
| 650 | 4 | |a survivin | |
| 650 | 7 | |a Survivin |2 NLM | |
| 650 | 7 | |a bcl-2-Associated X Protein |2 NLM | |
| 700 | 1 | |a Eslami, Farhad |e verfasserin |4 aut | |
| 700 | 1 | |a Babaei, Esmaeil |e verfasserin |4 aut | |
| 700 | 1 | |a Mostafavi, Hossein |e verfasserin |4 aut | |
| 700 | 1 | |a Mahdavi, Majid |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Anti-cancer agents in medicinal chemistry |d 2006 |g 24(2024), 3 vom: 29., Seite 203-212 |w (DE-627)NLM160693403 |x 1875-5992 |7 nnns |
| 773 | 1 | 8 | |g volume:24 |g year:2024 |g number:3 |g day:29 |g pages:203-212 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.2174/0118715206272359231121105713 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 24 |j 2024 |e 3 |b 29 |h 203-212 | ||