Cytotoxic Activity of Melatonin Alone and in Combination with Doxorubicin and/or Dexamethasone on Diffuse Large B-Cell Lymphoma Cells in In Vitro Conditions
Melatonin (MLT), a pineal gland hormone, not only regulates circadian and seasonal rhythms, but also plays an important role in many aspects of human physiology and pathophysiology. MLT is of great interest as a natural substance with anti-cancer activities. The aim of this study was to assess the c...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-08-01
|
| Series: | Journal of Personalized Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-4426/13/9/1314 |
| _version_ | 1797579314089164800 |
|---|---|
| author | Sylwia Mańka Piotr Smolewski Barbara Cebula-Obrzut Agata Majchrzak Klaudia Szmejda Magdalena Witkowska |
| author_facet | Sylwia Mańka Piotr Smolewski Barbara Cebula-Obrzut Agata Majchrzak Klaudia Szmejda Magdalena Witkowska |
| author_sort | Sylwia Mańka |
| collection | DOAJ |
| description | Melatonin (MLT), a pineal gland hormone, not only regulates circadian and seasonal rhythms, but also plays an important role in many aspects of human physiology and pathophysiology. MLT is of great interest as a natural substance with anti-cancer activities. The aim of this study was to assess the cytotoxicity and apoptosis of MLT, used alone or in combination with one of the most active anti-cancer drugs, doxorubicin (DOX), and a well-known anti-inflammatory drug, dexamethasone (DEX), on a diffuse large B-cell lymphoma (DLBCL)-derived cell line. The cytotoxicity and cell cycle distribution were measured using propidium iodide staining, while apoptosis was assessed using the annexin-V binding method. Additionally, to elucidate the mechanisms of action, caspase-3, -8, and -9 and a decline in the mitochondrial potential were determined using flow cytometry. MLT inhibited cell viability as well as induced apoptosis and cell cycle arrest at the G0/G1 phase. The pro-apoptotic effect was exerted through both the mitochondrial and caspase-dependent pathways. Furthermore, we observed increased cytotoxic and pro-apoptotic activity as well as the modulation of the cell cycle after the combination of MLT with DOX, DEX, or a combination of DOX + DEX, compared with both drugs or MLT used alone. Our findings confirm that MLT is a promising in vitro anti-tumour agent that requires further evaluation when used with other drugs active against DLBCL. |
| first_indexed | 2024-03-10T22:34:20Z |
| format | Article |
| id | doaj.art-9fe69fd6e0d1472e9bda764195198ac2 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T22:34:20Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-9fe69fd6e0d1472e9bda764195198ac22023-11-19T11:30:31ZengMDPI AGJournal of Personalized Medicine2075-44262023-08-01139131410.3390/jpm13091314Cytotoxic Activity of Melatonin Alone and in Combination with Doxorubicin and/or Dexamethasone on Diffuse Large B-Cell Lymphoma Cells in In Vitro ConditionsSylwia Mańka0Piotr Smolewski1Barbara Cebula-Obrzut2Agata Majchrzak3Klaudia Szmejda4Magdalena Witkowska5Department of Experimental Hematology, Medical University of Lodz, 93-510 Lodz, PolandDepartment of Experimental Hematology, Medical University of Lodz, 93-510 Lodz, PolandDepartment of Experimental Hematology, Medical University of Lodz, 93-510 Lodz, PolandDepartment of Hematology, Copernicus Memorial Hospital, 93-510 Lodz, PolandDepartment of Experimental Hematology, Medical University of Lodz, 93-510 Lodz, PolandDepartment of Experimental Hematology, Medical University of Lodz, 93-510 Lodz, PolandMelatonin (MLT), a pineal gland hormone, not only regulates circadian and seasonal rhythms, but also plays an important role in many aspects of human physiology and pathophysiology. MLT is of great interest as a natural substance with anti-cancer activities. The aim of this study was to assess the cytotoxicity and apoptosis of MLT, used alone or in combination with one of the most active anti-cancer drugs, doxorubicin (DOX), and a well-known anti-inflammatory drug, dexamethasone (DEX), on a diffuse large B-cell lymphoma (DLBCL)-derived cell line. The cytotoxicity and cell cycle distribution were measured using propidium iodide staining, while apoptosis was assessed using the annexin-V binding method. Additionally, to elucidate the mechanisms of action, caspase-3, -8, and -9 and a decline in the mitochondrial potential were determined using flow cytometry. MLT inhibited cell viability as well as induced apoptosis and cell cycle arrest at the G0/G1 phase. The pro-apoptotic effect was exerted through both the mitochondrial and caspase-dependent pathways. Furthermore, we observed increased cytotoxic and pro-apoptotic activity as well as the modulation of the cell cycle after the combination of MLT with DOX, DEX, or a combination of DOX + DEX, compared with both drugs or MLT used alone. Our findings confirm that MLT is a promising in vitro anti-tumour agent that requires further evaluation when used with other drugs active against DLBCL.https://www.mdpi.com/2075-4426/13/9/1314melatonindiffuse large B-cell lymphomaapoptosiscell cycledoxorubicindexamethasone |
| spellingShingle | Sylwia Mańka Piotr Smolewski Barbara Cebula-Obrzut Agata Majchrzak Klaudia Szmejda Magdalena Witkowska Cytotoxic Activity of Melatonin Alone and in Combination with Doxorubicin and/or Dexamethasone on Diffuse Large B-Cell Lymphoma Cells in In Vitro Conditions Journal of Personalized Medicine melatonin diffuse large B-cell lymphoma apoptosis cell cycle doxorubicin dexamethasone |
| title | Cytotoxic Activity of Melatonin Alone and in Combination with Doxorubicin and/or Dexamethasone on Diffuse Large B-Cell Lymphoma Cells in In Vitro Conditions |
| title_full | Cytotoxic Activity of Melatonin Alone and in Combination with Doxorubicin and/or Dexamethasone on Diffuse Large B-Cell Lymphoma Cells in In Vitro Conditions |
| title_fullStr | Cytotoxic Activity of Melatonin Alone and in Combination with Doxorubicin and/or Dexamethasone on Diffuse Large B-Cell Lymphoma Cells in In Vitro Conditions |
| title_full_unstemmed | Cytotoxic Activity of Melatonin Alone and in Combination with Doxorubicin and/or Dexamethasone on Diffuse Large B-Cell Lymphoma Cells in In Vitro Conditions |
| title_short | Cytotoxic Activity of Melatonin Alone and in Combination with Doxorubicin and/or Dexamethasone on Diffuse Large B-Cell Lymphoma Cells in In Vitro Conditions |
| title_sort | cytotoxic activity of melatonin alone and in combination with doxorubicin and or dexamethasone on diffuse large b cell lymphoma cells in in vitro conditions |
| topic | melatonin diffuse large B-cell lymphoma apoptosis cell cycle doxorubicin dexamethasone |
| url | https://www.mdpi.com/2075-4426/13/9/1314 |
| work_keys_str_mv | AT sylwiamanka cytotoxicactivityofmelatoninaloneandincombinationwithdoxorubicinandordexamethasoneondiffuselargebcelllymphomacellsininvitroconditions AT piotrsmolewski cytotoxicactivityofmelatoninaloneandincombinationwithdoxorubicinandordexamethasoneondiffuselargebcelllymphomacellsininvitroconditions AT barbaracebulaobrzut cytotoxicactivityofmelatoninaloneandincombinationwithdoxorubicinandordexamethasoneondiffuselargebcelllymphomacellsininvitroconditions AT agatamajchrzak cytotoxicactivityofmelatoninaloneandincombinationwithdoxorubicinandordexamethasoneondiffuselargebcelllymphomacellsininvitroconditions AT klaudiaszmejda cytotoxicactivityofmelatoninaloneandincombinationwithdoxorubicinandordexamethasoneondiffuselargebcelllymphomacellsininvitroconditions AT magdalenawitkowska cytotoxicactivityofmelatoninaloneandincombinationwithdoxorubicinandordexamethasoneondiffuselargebcelllymphomacellsininvitroconditions |