Cytotoxic, Antioxidant, and Anti-Genotoxic Properties of Combretastatin A4 in Human Peripheral Blood Mononuclear Cells: A Comprehensive In Vitro Study
Despite significant advances in drug discovery and the promising antitumor potential of combretastatin A4 (CA-4), which selectively targets rapidly dividing cancer cells, CA-4’s effects on non-dividing human cells, such as peripheral blood mononuclear cells (PBMCs), remain unclear. The aim of this s...
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2024-11-01
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| author | Petar Popović Andrea Pirković Dijana Topalović Lada Živković Milica Marković Biljana Spremo-Potparević |
| author_facet | Petar Popović Andrea Pirković Dijana Topalović Lada Živković Milica Marković Biljana Spremo-Potparević |
| author_sort | Petar Popović |
| collection | DOAJ |
| description | Despite significant advances in drug discovery and the promising antitumor potential of combretastatin A4 (CA-4), which selectively targets rapidly dividing cancer cells, CA-4’s effects on non-dividing human cells, such as peripheral blood mononuclear cells (PBMCs), remain unclear. The aim of this study is to evaluate the in vitro bioactivity of CA-4 in human PBMCs, focusing on its antigenotoxic and antioxidant properties, while comparing its cytotoxic potency against PBMCs, cancer cell lines (JAR and HeLa), and the normal trophoblast cell line HTR-8/SVneo. Cell viability and metabolic activity were evaluated using the MTT assay. ROS production in PBMCs was measured using the H2DCFDA assay, and DNA damage was assessed using the Comet assay. CA-4 showed cytotoxicity in PBMCs and HTR-8/SVneo cells at concentrations above 200 µM, while cancer cells, JAR and HeLa, showed cytotoxicity at 100 µM and 1 µM, respectively. CA-4 also reduced ROS levels in PBMCs under oxidative stress and showed antioxidant effects at concentrations from 1 to 200 µM. In addition, CA-4 showed antigenotoxic effects against H<sub>2</sub>O<sub>2</sub>-induced DNA damage in PBMCs at concentrations of up to 1 µM. CA-4 exhibited lower cytotoxicity in human PBMCs compared to cancer cells, inhibited ROS production, and showed antioxidant and antigenotoxic properties, providing insight into its potential therapeutic efficacy and safety. |
| format | Article |
| id | doaj-art-486d79a4a32d4f3aa609ee0a480eba7d |
| institution | DOAJ |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-486d79a4a32d4f3aa609ee0a480eba7d2025-08-20T02:55:31ZengMDPI AGBiomolecules2218-273X2024-11-011412153510.3390/biom14121535Cytotoxic, Antioxidant, and Anti-Genotoxic Properties of Combretastatin A4 in Human Peripheral Blood Mononuclear Cells: A Comprehensive In Vitro StudyPetar Popović0Andrea Pirković1Dijana Topalović2Lada Živković3Milica Marković4Biljana Spremo-Potparević5Department of Pathobiology, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, SerbiaDepartment for Biology of Reproduction, Institute for the Application of Nuclear Energy-INEP, University of Belgrade, 11000 Belgrade, SerbiaDepartment of Pathobiology, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, SerbiaDepartment of Pathobiology, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, SerbiaDepartment of Pathobiology, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, SerbiaDepartment of Pathobiology, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, SerbiaDespite significant advances in drug discovery and the promising antitumor potential of combretastatin A4 (CA-4), which selectively targets rapidly dividing cancer cells, CA-4’s effects on non-dividing human cells, such as peripheral blood mononuclear cells (PBMCs), remain unclear. The aim of this study is to evaluate the in vitro bioactivity of CA-4 in human PBMCs, focusing on its antigenotoxic and antioxidant properties, while comparing its cytotoxic potency against PBMCs, cancer cell lines (JAR and HeLa), and the normal trophoblast cell line HTR-8/SVneo. Cell viability and metabolic activity were evaluated using the MTT assay. ROS production in PBMCs was measured using the H2DCFDA assay, and DNA damage was assessed using the Comet assay. CA-4 showed cytotoxicity in PBMCs and HTR-8/SVneo cells at concentrations above 200 µM, while cancer cells, JAR and HeLa, showed cytotoxicity at 100 µM and 1 µM, respectively. CA-4 also reduced ROS levels in PBMCs under oxidative stress and showed antioxidant effects at concentrations from 1 to 200 µM. In addition, CA-4 showed antigenotoxic effects against H<sub>2</sub>O<sub>2</sub>-induced DNA damage in PBMCs at concentrations of up to 1 µM. CA-4 exhibited lower cytotoxicity in human PBMCs compared to cancer cells, inhibited ROS production, and showed antioxidant and antigenotoxic properties, providing insight into its potential therapeutic efficacy and safety.https://www.mdpi.com/2218-273X/14/12/1535combretastatin A4PBMCoxidative stressgenotoxicitytrophoblast |
| spellingShingle | Petar Popović Andrea Pirković Dijana Topalović Lada Živković Milica Marković Biljana Spremo-Potparević Cytotoxic, Antioxidant, and Anti-Genotoxic Properties of Combretastatin A4 in Human Peripheral Blood Mononuclear Cells: A Comprehensive In Vitro Study Biomolecules combretastatin A4 PBMC oxidative stress genotoxicity trophoblast |
| title | Cytotoxic, Antioxidant, and Anti-Genotoxic Properties of Combretastatin A4 in Human Peripheral Blood Mononuclear Cells: A Comprehensive In Vitro Study |
| title_full | Cytotoxic, Antioxidant, and Anti-Genotoxic Properties of Combretastatin A4 in Human Peripheral Blood Mononuclear Cells: A Comprehensive In Vitro Study |
| title_fullStr | Cytotoxic, Antioxidant, and Anti-Genotoxic Properties of Combretastatin A4 in Human Peripheral Blood Mononuclear Cells: A Comprehensive In Vitro Study |
| title_full_unstemmed | Cytotoxic, Antioxidant, and Anti-Genotoxic Properties of Combretastatin A4 in Human Peripheral Blood Mononuclear Cells: A Comprehensive In Vitro Study |
| title_short | Cytotoxic, Antioxidant, and Anti-Genotoxic Properties of Combretastatin A4 in Human Peripheral Blood Mononuclear Cells: A Comprehensive In Vitro Study |
| title_sort | cytotoxic antioxidant and anti genotoxic properties of combretastatin a4 in human peripheral blood mononuclear cells a comprehensive in vitro study |
| topic | combretastatin A4 PBMC oxidative stress genotoxicity trophoblast |
| url | https://www.mdpi.com/2218-273X/14/12/1535 |
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