Synthetic cannabinoids JWH-018, JWH-122, UR-144 and the phytocannabinoid THC activate apoptosis in placental cells
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10400.8/5103 |
Resumo: | This work was financed by the European Regional Development Fund (ERDF) through the Operational Competitiveness Factors Program—COMPETE and by National Funds through FCT—Foundation for Science and Technology within the scope of the project “PTDC/DTPFTO/5651/2014-POCI-01-0145-FEDER-016562” and projects NORTE-01-0145-FEDER-000024, supported by Norte Portugal Regional Operational Program (NORTE2020), under the PORTUGAL 2020 Partnership Agreement, through ERDF and UID/MULTI/04378/2019 from FCT/MEC. We also thank FCT support, through the strategic project UID/MAR/04292/2019 granted to MARE and UID/MULTI/04046/2019 to BioISI. Cristina Amaral thanks FCT for the contract under the funding program (DL 57/2016 – Norma Transitória) and through the Post-doc grant (SFRH/BPD/98304/2013). The authors thank the toxicology sector of the “Laboratório de Polícia Científica da Polícia Judiciária” for providing the smart shop product, within the protocol established with the “Faculdade de Ciências da Universidade de Lisboa” and “Faculdade de Farmácia da Universidade do Porto”. |
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Synthetic cannabinoids JWH-018, JWH-122, UR-144 and the phytocannabinoid THC activate apoptosis in placental cellsΔ9-TetrahydrocannabinolSynthetic cannabinoidsJWH-018JWH-122UR-144BeWoCellsCytotrophoblastsPlacentaApoptosisThis work was financed by the European Regional Development Fund (ERDF) through the Operational Competitiveness Factors Program—COMPETE and by National Funds through FCT—Foundation for Science and Technology within the scope of the project “PTDC/DTPFTO/5651/2014-POCI-01-0145-FEDER-016562” and projects NORTE-01-0145-FEDER-000024, supported by Norte Portugal Regional Operational Program (NORTE2020), under the PORTUGAL 2020 Partnership Agreement, through ERDF and UID/MULTI/04378/2019 from FCT/MEC. We also thank FCT support, through the strategic project UID/MAR/04292/2019 granted to MARE and UID/MULTI/04046/2019 to BioISI. Cristina Amaral thanks FCT for the contract under the funding program (DL 57/2016 – Norma Transitória) and through the Post-doc grant (SFRH/BPD/98304/2013). The authors thank the toxicology sector of the “Laboratório de Polícia Científica da Polícia Judiciária” for providing the smart shop product, within the protocol established with the “Faculdade de Ciências da Universidade de Lisboa” and “Faculdade de Farmácia da Universidade do Porto”.The increasing use of synthetic cannabinoids (SCBs) in recreational settings is becoming a new paradigm of drug abuse. Although SCBs effects mimic those of the Cannabis sativa plant, these drugs are frequently more potent and hazardous. It is known that endocannabinoid signalling plays a crucial role in diverse reproductive events such as placental development. Moreover, the negative impact of the phytocannabinoid Δ9-tetrahydrocannabinol (THC) in pregnancy outcome, leading to prematurity, intrauterine growth restriction and low birth weight is well recognized, which makes women of childbearing age a sensitive group to developmental adverse effects of cannabinoids. Placental trophoblast turnover relies on regulated processes of proliferation and apoptosis for normal placental development. Here, we explored the impact of the SCBs JWH-018, JWH-122 and UR-144 and of the phytocannabinoid THC in BeWo cell line, a human placental cytotrophoblast cell model. All the cannabinoids caused a significant decrease in cell viability without LDH release, though this effect was only detected for the highest concentrations of THC. Moreover, a cell cycle arrest at the G2/M phase was also observed. JWH-018 and JWH-122 increased reactive oxygen species (ROS) production and THC, UR-144 and JWH-122 caused loss of mitochondrial membrane potential. All the compounds were able to induce caspase-9 activation. The involvement of apoptotic pathways was further confirmed through the significant increase in caspase -3/-7 activities. For UR-144, this effect was reversed by the CB1 antagonist AM281, for JWH-018 and THC this effect was mediated by both cannabinoid receptors CB1 and CB2 while for JWH-122 it was cannabinoid receptor-independent. This work demonstrates that THC and SCBs are able to induce apoptotic cell death. Although they may act through different mechanisms and potencies, the studied cannabinoids have the potential to disrupt gestational fundamental events.ElsevierIC-OnlineAlmada, AlmadaAlves, PatríciaFonseca, Bruno M.Carvalho, FélixQueirós, Cláudio R.Gaspar, HelenaAmaral, CristinaTeixeira, Natércia A.Correia-da-Silva, Georgina2020-08-19T13:57:00Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.8/5103engAlmada, M., Alves, P., Fonseca, B. M., Carvalho, F., Queirós, C. R., Gaspar, H., Amaral, C., Teixeira, N. A., & Correia-da-Silva, G. (2020). Synthetic cannabinoids JWH-018, JWH-122, UR-144 and the phytocannabinoid THC activate apoptosis in placental cells. Toxicology letters, 319, 129–137. https://doi.org/10.1016/j.toxlet.2019.11.0040378-427410.1016/j.toxlet.2019.11.004metadata only accessinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-01-17T15:50:35Zoai:iconline.ipleiria.pt:10400.8/5103Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T01:48:46.058928Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Synthetic cannabinoids JWH-018, JWH-122, UR-144 and the phytocannabinoid THC activate apoptosis in placental cells |
| title |
Synthetic cannabinoids JWH-018, JWH-122, UR-144 and the phytocannabinoid THC activate apoptosis in placental cells |
| spellingShingle |
Synthetic cannabinoids JWH-018, JWH-122, UR-144 and the phytocannabinoid THC activate apoptosis in placental cells Almada, Almada Δ9-Tetrahydrocannabinol Synthetic cannabinoids JWH-018 JWH-122 UR-144 BeWo Cells Cytotrophoblasts Placenta Apoptosis |
| title_short |
Synthetic cannabinoids JWH-018, JWH-122, UR-144 and the phytocannabinoid THC activate apoptosis in placental cells |
| title_full |
Synthetic cannabinoids JWH-018, JWH-122, UR-144 and the phytocannabinoid THC activate apoptosis in placental cells |
| title_fullStr |
Synthetic cannabinoids JWH-018, JWH-122, UR-144 and the phytocannabinoid THC activate apoptosis in placental cells |
| title_full_unstemmed |
Synthetic cannabinoids JWH-018, JWH-122, UR-144 and the phytocannabinoid THC activate apoptosis in placental cells |
| title_sort |
Synthetic cannabinoids JWH-018, JWH-122, UR-144 and the phytocannabinoid THC activate apoptosis in placental cells |
| author |
Almada, Almada |
| author_facet |
Almada, Almada Alves, Patrícia Fonseca, Bruno M. Carvalho, Félix Queirós, Cláudio R. Gaspar, Helena Amaral, Cristina Teixeira, Natércia A. Correia-da-Silva, Georgina |
| author_role |
author |
| author2 |
Alves, Patrícia Fonseca, Bruno M. Carvalho, Félix Queirós, Cláudio R. Gaspar, Helena Amaral, Cristina Teixeira, Natércia A. Correia-da-Silva, Georgina |
| author2_role |
author author author author author author author author |
| dc.contributor.none.fl_str_mv |
IC-Online |
| dc.contributor.author.fl_str_mv |
Almada, Almada Alves, Patrícia Fonseca, Bruno M. Carvalho, Félix Queirós, Cláudio R. Gaspar, Helena Amaral, Cristina Teixeira, Natércia A. Correia-da-Silva, Georgina |
| dc.subject.por.fl_str_mv |
Δ9-Tetrahydrocannabinol Synthetic cannabinoids JWH-018 JWH-122 UR-144 BeWo Cells Cytotrophoblasts Placenta Apoptosis |
| topic |
Δ9-Tetrahydrocannabinol Synthetic cannabinoids JWH-018 JWH-122 UR-144 BeWo Cells Cytotrophoblasts Placenta Apoptosis |
| description |
This work was financed by the European Regional Development Fund (ERDF) through the Operational Competitiveness Factors Program—COMPETE and by National Funds through FCT—Foundation for Science and Technology within the scope of the project “PTDC/DTPFTO/5651/2014-POCI-01-0145-FEDER-016562” and projects NORTE-01-0145-FEDER-000024, supported by Norte Portugal Regional Operational Program (NORTE2020), under the PORTUGAL 2020 Partnership Agreement, through ERDF and UID/MULTI/04378/2019 from FCT/MEC. We also thank FCT support, through the strategic project UID/MAR/04292/2019 granted to MARE and UID/MULTI/04046/2019 to BioISI. Cristina Amaral thanks FCT for the contract under the funding program (DL 57/2016 – Norma Transitória) and through the Post-doc grant (SFRH/BPD/98304/2013). The authors thank the toxicology sector of the “Laboratório de Polícia Científica da Polícia Judiciária” for providing the smart shop product, within the protocol established with the “Faculdade de Ciências da Universidade de Lisboa” and “Faculdade de Farmácia da Universidade do Porto”. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020-08-19T13:57:00Z 2020 2020-01-01T00:00:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10400.8/5103 |
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http://hdl.handle.net/10400.8/5103 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
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Almada, M., Alves, P., Fonseca, B. M., Carvalho, F., Queirós, C. R., Gaspar, H., Amaral, C., Teixeira, N. A., & Correia-da-Silva, G. (2020). Synthetic cannabinoids JWH-018, JWH-122, UR-144 and the phytocannabinoid THC activate apoptosis in placental cells. Toxicology letters, 319, 129–137. https://doi.org/10.1016/j.toxlet.2019.11.004 0378-4274 10.1016/j.toxlet.2019.11.004 |
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metadata only access |
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openAccess |
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application/pdf |
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Elsevier |
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Elsevier |
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