MECHANISMS OF APOPTOSIS DYSREGULATION IN CANCER CELLS UNDER THE CONDITIONS OF REDOX STATUS MODULATION
Introduction. Changes in the redox status of tumor cells can be used as one of the molecular mechanisms of apoptosis aimed at increasing the susceptibility of tumor cells to chemotherapeutic agents. Purpose: to study the mechanisms of dysregulation of apoptosis in P19 tumor cells under the condition...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | Russian |
| Published: |
Russian Academy of Sciences, Tomsk National Research Medical Center
2016-12-01
|
| Series: | Сибирский онкологический журнал |
| Subjects: | |
| Online Access: | https://www.siboncoj.ru/jour/article/view/445 |
| _version_ | 1826563799622090752 |
|---|---|
| author | D. S. Orlov N. V. Ryazantseva E. A. Stepovaya O. L. Nosareva E. V. Shakhristova V. V. Ivanov |
| author_facet | D. S. Orlov N. V. Ryazantseva E. A. Stepovaya O. L. Nosareva E. V. Shakhristova V. V. Ivanov |
| author_sort | D. S. Orlov |
| collection | DOAJ |
| description | Introduction. Changes in the redox status of tumor cells can be used as one of the molecular mechanisms of apoptosis aimed at increasing the susceptibility of tumor cells to chemotherapeutic agents. Purpose: to study the mechanisms of dysregulation of apoptosis in P19 tumor cells under the conditions of redox status modulation. Material and methods. Apoptosis in P19 tumor cells was assessed by flow cytometry analysis. The number of annexin-positive cells, the expression of CD95 and CD120, as well as the intracellular calcium ion concentration and the percentage of cells with reduced mitochondrial transmembrane potential were measured. The protein-glutathione mixed-disulfide level and the GSH/GSSG ratio were determined by spectrophotometry. To modulate redox status of cells, the protector and blocker of SH-groups, or N-acetylcysteine were used. Results. Incubation of cultures in the presence of SH-group blocker resulted in the imbalance in the glutathione system with increased concentration of glutathionylated proteins. A decreased redox status led to an increased CD95 and CD120 expression levels on the membrane of P19 tumor cells, as well as to decreased mitochondrial potential and increased intracellular calcium ion concentration, thus contributing to the launch of a P19 tumor cells. The presence of SH-group blocker and N-acetylcysteine resulted in an increased number of annexinpositive cells. Conclusion. Along with the development of oxidative stress, the molecular redox-dependent mechanisms of apoptosis dysregulation through the mitochondrial and receptor-mediated pathways were identified in the P19 tumor cells. |
| first_indexed | 2024-04-10T01:54:19Z |
| format | Article |
| id | doaj.art-79e1dcb2517444379fdcc3145835aec1 |
| institution | Directory Open Access Journal |
| issn | 1814-4861 2312-3168 |
| language | Russian |
| last_indexed | 2025-03-14T10:09:42Z |
| publishDate | 2016-12-01 |
| publisher | Russian Academy of Sciences, Tomsk National Research Medical Center |
| record_format | Article |
| series | Сибирский онкологический журнал |
| spelling | doaj.art-79e1dcb2517444379fdcc3145835aec12025-03-02T11:16:08ZrusRussian Academy of Sciences, Tomsk National Research Medical CenterСибирский онкологический журнал1814-48612312-31682016-12-01156424710.21294/1814-4861-2016-15-6-42-47396MECHANISMS OF APOPTOSIS DYSREGULATION IN CANCER CELLS UNDER THE CONDITIONS OF REDOX STATUS MODULATIOND. S. Orlov0N. V. Ryazantseva1E. A. Stepovaya2O. L. Nosareva3E. V. Shakhristova4V. V. Ivanov5Siberian State Medical UniversitySiberian Federal University; Krasnoyarsk State Medical University named after Professor V.F. Voino-YasenetskySiberian State Medical UniversitySiberian State Medical UniversitySiberian State Medical UniversitySiberian State Medical UniversityIntroduction. Changes in the redox status of tumor cells can be used as one of the molecular mechanisms of apoptosis aimed at increasing the susceptibility of tumor cells to chemotherapeutic agents. Purpose: to study the mechanisms of dysregulation of apoptosis in P19 tumor cells under the conditions of redox status modulation. Material and methods. Apoptosis in P19 tumor cells was assessed by flow cytometry analysis. The number of annexin-positive cells, the expression of CD95 and CD120, as well as the intracellular calcium ion concentration and the percentage of cells with reduced mitochondrial transmembrane potential were measured. The protein-glutathione mixed-disulfide level and the GSH/GSSG ratio were determined by spectrophotometry. To modulate redox status of cells, the protector and blocker of SH-groups, or N-acetylcysteine were used. Results. Incubation of cultures in the presence of SH-group blocker resulted in the imbalance in the glutathione system with increased concentration of glutathionylated proteins. A decreased redox status led to an increased CD95 and CD120 expression levels on the membrane of P19 tumor cells, as well as to decreased mitochondrial potential and increased intracellular calcium ion concentration, thus contributing to the launch of a P19 tumor cells. The presence of SH-group blocker and N-acetylcysteine resulted in an increased number of annexinpositive cells. Conclusion. Along with the development of oxidative stress, the molecular redox-dependent mechanisms of apoptosis dysregulation through the mitochondrial and receptor-mediated pathways were identified in the P19 tumor cells.https://www.siboncoj.ru/jour/article/view/445apoptosisglutathionylated proteinoxidative stresstumor growth |
| spellingShingle | D. S. Orlov N. V. Ryazantseva E. A. Stepovaya O. L. Nosareva E. V. Shakhristova V. V. Ivanov MECHANISMS OF APOPTOSIS DYSREGULATION IN CANCER CELLS UNDER THE CONDITIONS OF REDOX STATUS MODULATION Сибирский онкологический журнал apoptosis glutathionylated protein oxidative stress tumor growth |
| title | MECHANISMS OF APOPTOSIS DYSREGULATION IN CANCER CELLS UNDER THE CONDITIONS OF REDOX STATUS MODULATION |
| title_full | MECHANISMS OF APOPTOSIS DYSREGULATION IN CANCER CELLS UNDER THE CONDITIONS OF REDOX STATUS MODULATION |
| title_fullStr | MECHANISMS OF APOPTOSIS DYSREGULATION IN CANCER CELLS UNDER THE CONDITIONS OF REDOX STATUS MODULATION |
| title_full_unstemmed | MECHANISMS OF APOPTOSIS DYSREGULATION IN CANCER CELLS UNDER THE CONDITIONS OF REDOX STATUS MODULATION |
| title_short | MECHANISMS OF APOPTOSIS DYSREGULATION IN CANCER CELLS UNDER THE CONDITIONS OF REDOX STATUS MODULATION |
| title_sort | mechanisms of apoptosis dysregulation in cancer cells under the conditions of redox status modulation |
| topic | apoptosis glutathionylated protein oxidative stress tumor growth |
| url | https://www.siboncoj.ru/jour/article/view/445 |
| work_keys_str_mv | AT dsorlov mechanismsofapoptosisdysregulationincancercellsundertheconditionsofredoxstatusmodulation AT nvryazantseva mechanismsofapoptosisdysregulationincancercellsundertheconditionsofredoxstatusmodulation AT eastepovaya mechanismsofapoptosisdysregulationincancercellsundertheconditionsofredoxstatusmodulation AT olnosareva mechanismsofapoptosisdysregulationincancercellsundertheconditionsofredoxstatusmodulation AT evshakhristova mechanismsofapoptosisdysregulationincancercellsundertheconditionsofredoxstatusmodulation AT vvivanov mechanismsofapoptosisdysregulationincancercellsundertheconditionsofredoxstatusmodulation |