Cannabidiol and Its Combinations with Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis and Inhibit Activation of NF-κB Signaling in Vulvar Squamous Cell Carcinoma
Vulvar squamous cell carcinoma (VSCC) is a rare malignancy with a relatively good prognosis. However, the prognosis remains poor for elderly patients and those with a significant depth of tumor invasion; thus, novel treatment modalities are needed. The aim of this study was to analyze the impact of...
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MDPI AG
2022-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/24/8779 |
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| author | Violetta Krajka-Kuźniak Katarzyna Papierska Maria Narożna Anna Jelińska Aleksandra Majchrzak-Celińska |
| author_facet | Violetta Krajka-Kuźniak Katarzyna Papierska Maria Narożna Anna Jelińska Aleksandra Majchrzak-Celińska |
| author_sort | Violetta Krajka-Kuźniak |
| collection | DOAJ |
| description | Vulvar squamous cell carcinoma (VSCC) is a rare malignancy with a relatively good prognosis. However, the prognosis remains poor for elderly patients and those with a significant depth of tumor invasion; thus, novel treatment modalities are needed. The aim of this study was to analyze the impact of cannabidiol (CBD) and its combination with NSAIDs, diclofenac (DIC) and ibuprofen (IBU) on VSCC cells. In this regard, the MTT test was applied for cytotoxicity analysis. Moreover, the influence of CBD, DIC and IBU, as well as their combinations, on apoptosis and cell cycle distribution were analyzed by flow cytometry. The mechanisms of action of the analyzed compounds, including their impact on NF-κB signaling, p53 and COX-2 expression were evaluated using Western blot. This study shows that CBD and its combinations with NSAIDs are cytotoxic to A431 cells, but they also reduce, in a dose-dependent manner, the viability of immortalized keratinocyte HaCaT cells, and human umbilical vein cell line, EA.hy926. Moreover, the compounds and their combinations induced apoptosis, diminished the NF-κB signaling activation and reduced COX-2 expression. We conclude that CBD and its combination with DIC or IBU are promising candidates for the adjuvant treatment of high-risk VSCC patients. However, their impact on non-cancerous cells requires careful evaluation. |
| first_indexed | 2024-03-09T16:02:19Z |
| format | Article |
| id | doaj.art-74de27bc7a684a46960137b37a17ea87 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T16:02:19Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-74de27bc7a684a46960137b37a17ea872023-11-24T16:57:17ZengMDPI AGMolecules1420-30492022-12-012724877910.3390/molecules27248779Cannabidiol and Its Combinations with Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis and Inhibit Activation of NF-κB Signaling in Vulvar Squamous Cell CarcinomaVioletta Krajka-Kuźniak0Katarzyna Papierska1Maria Narożna2Anna Jelińska3Aleksandra Majchrzak-Celińska4Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, 60-781 Poznań, PolandDepartment of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, 60-781 Poznań, PolandProgram in Cell Cycle and Cancer Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USADepartment of Pharmaceutical Chemistry, Poznan University of Medical Sciences, 60-780 Poznań, PolandDepartment of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, 60-781 Poznań, PolandVulvar squamous cell carcinoma (VSCC) is a rare malignancy with a relatively good prognosis. However, the prognosis remains poor for elderly patients and those with a significant depth of tumor invasion; thus, novel treatment modalities are needed. The aim of this study was to analyze the impact of cannabidiol (CBD) and its combination with NSAIDs, diclofenac (DIC) and ibuprofen (IBU) on VSCC cells. In this regard, the MTT test was applied for cytotoxicity analysis. Moreover, the influence of CBD, DIC and IBU, as well as their combinations, on apoptosis and cell cycle distribution were analyzed by flow cytometry. The mechanisms of action of the analyzed compounds, including their impact on NF-κB signaling, p53 and COX-2 expression were evaluated using Western blot. This study shows that CBD and its combinations with NSAIDs are cytotoxic to A431 cells, but they also reduce, in a dose-dependent manner, the viability of immortalized keratinocyte HaCaT cells, and human umbilical vein cell line, EA.hy926. Moreover, the compounds and their combinations induced apoptosis, diminished the NF-κB signaling activation and reduced COX-2 expression. We conclude that CBD and its combination with DIC or IBU are promising candidates for the adjuvant treatment of high-risk VSCC patients. However, their impact on non-cancerous cells requires careful evaluation.https://www.mdpi.com/1420-3049/27/24/8779cannabidioldiclofenacibuprofenA431vulvar squamous cell carcinomainflammation |
| spellingShingle | Violetta Krajka-Kuźniak Katarzyna Papierska Maria Narożna Anna Jelińska Aleksandra Majchrzak-Celińska Cannabidiol and Its Combinations with Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis and Inhibit Activation of NF-κB Signaling in Vulvar Squamous Cell Carcinoma Molecules cannabidiol diclofenac ibuprofen A431 vulvar squamous cell carcinoma inflammation |
| title | Cannabidiol and Its Combinations with Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis and Inhibit Activation of NF-κB Signaling in Vulvar Squamous Cell Carcinoma |
| title_full | Cannabidiol and Its Combinations with Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis and Inhibit Activation of NF-κB Signaling in Vulvar Squamous Cell Carcinoma |
| title_fullStr | Cannabidiol and Its Combinations with Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis and Inhibit Activation of NF-κB Signaling in Vulvar Squamous Cell Carcinoma |
| title_full_unstemmed | Cannabidiol and Its Combinations with Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis and Inhibit Activation of NF-κB Signaling in Vulvar Squamous Cell Carcinoma |
| title_short | Cannabidiol and Its Combinations with Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis and Inhibit Activation of NF-κB Signaling in Vulvar Squamous Cell Carcinoma |
| title_sort | cannabidiol and its combinations with nonsteroidal anti inflammatory drugs induce apoptosis and inhibit activation of nf κb signaling in vulvar squamous cell carcinoma |
| topic | cannabidiol diclofenac ibuprofen A431 vulvar squamous cell carcinoma inflammation |
| url | https://www.mdpi.com/1420-3049/27/24/8779 |
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