Metformin attenuates V-domain Ig suppressor of T-cell activation through the aryl hydrocarbon receptor pathway in Melanoma: In Vivo and In Vitro Studies
Melanoma is an aggressive skin cancer with a high rate of metastasis to other organs. Recent studies specified the overexpression of V-domain Ig suppressor of T-cell activation (VISTA) and Aryl Hydrocarbon Receptor (AHR) in melanoma. Metformin shows anti-tumor activities in several cancer types. How...
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| مؤلفون آخرون: | , , , , , , , |
| التنسيق: | article |
| منشور في: |
2021
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| الموضوعات: | |
| الوصول للمادة أونلاين: | http://dx.doi.org/10.1016/j.jsps.2021.12.014 https://www.sciencedirect.com/science/article/pii/S1319016421002632 http://hdl.handle.net/10576/41172 |
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| _version_ | 1857415087435808768 |
|---|---|
| author | Fawaz E., Alanazi |
| author2 | As Sobeai, Homood M. Alhazzani, Khalid Al-Dhfyan, Abdullah Alshammari, Musaad A Alotaibi, Moureq Al-hosaini, Khaled Korashy, Hesham M. Alhoshani, Ali |
| author2_role | author author author author author author author author |
| author_facet | Fawaz E., Alanazi As Sobeai, Homood M. Alhazzani, Khalid Al-Dhfyan, Abdullah Alshammari, Musaad A Alotaibi, Moureq Al-hosaini, Khaled Korashy, Hesham M. Alhoshani, Ali |
| author_role | author |
| dc.creator.none.fl_str_mv | Fawaz E., Alanazi As Sobeai, Homood M. Alhazzani, Khalid Al-Dhfyan, Abdullah Alshammari, Musaad A Alotaibi, Moureq Al-hosaini, Khaled Korashy, Hesham M. Alhoshani, Ali |
| dc.date.none.fl_str_mv | 2021-12-31 2023-03-20T06:35:53Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://dx.doi.org/10.1016/j.jsps.2021.12.014 Alanazi, F. E., Sobeai, H. M. A., Alhazzani, K., Al-Dhfyan, A., Alshammari, M. A., Alotaibi, M., ... & Alhoshani, A. (2022). Metformin attenuates V-domain Ig suppressor of T-cell activation through the aryl hydrocarbon receptor pathway in Melanoma: In Vivo and In Vitro Studies. Saudi Pharmaceutical Journal, 30(2), 138-149. 1319-0164 https://www.sciencedirect.com/science/article/pii/S1319016421002632 http://hdl.handle.net/10576/41172 138-149 2 30 |
| dc.language.none.fl_str_mv | en |
| dc.publisher.none.fl_str_mv | Elsevier |
| dc.rights.none.fl_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | VISTA AHR CYP1A1 IDO1 Metformin CHL-1 B16 Melanoma |
| dc.title.none.fl_str_mv | Metformin attenuates V-domain Ig suppressor of T-cell activation through the aryl hydrocarbon receptor pathway in Melanoma: In Vivo and In Vitro Studies |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | Melanoma is an aggressive skin cancer with a high rate of metastasis to other organs. Recent studies specified the overexpression of V-domain Ig suppressor of T-cell activation (VISTA) and Aryl Hydrocarbon Receptor (AHR) in melanoma. Metformin shows anti-tumor activities in several cancer types. However, the mechanism is unclear. This study aims to investigate the inhibitory effect of metformin on VISTA via AHR in melanoma cells (CHL-1, B16) and animal models. VISTA and AHR levels were assessed by qPCR, Western blot, immunofluorescence microscope, flow cytometry, and immunohistochemistry. Here, metformin significantly decreased VISTA and AHR levels in vitro and in vivo. Furthermore, metformin inhibited all AHR-regulated genes. VISTA levels were dramatically inhibited by AHR modulations using shRNA and αNF, confirming the central role of AHR in VISTA. Finally, melanoma cells were xenografted in C57BL/6 and nude mice. Metformin significantly reduced the tumor volume and growth rate. Likewise, VISTA and AHR-regulated protein levels were suppressed in both models. These findings demonstrate for the first time that VISTA is suppressed by metformin and identified a new regulatory mechanism through AHR. The data suggest that metformin could be a new potential therapeutic strategy to treat melanoma patients combined with targeted immune checkpoint inhibitors. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | qu_78704e13064c30b0daf9427e0e457e7e |
| identifier_str_mv | Alanazi, F. E., Sobeai, H. M. A., Alhazzani, K., Al-Dhfyan, A., Alshammari, M. A., Alotaibi, M., ... & Alhoshani, A. (2022). Metformin attenuates V-domain Ig suppressor of T-cell activation through the aryl hydrocarbon receptor pathway in Melanoma: In Vivo and In Vitro Studies. Saudi Pharmaceutical Journal, 30(2), 138-149. 1319-0164 138-149 2 30 |
| language_invalid_str_mv | en |
| network_acronym_str | qu |
| network_name_str | Qatar University repository |
| oai_identifier_str | oai:qspace.qu.edu.qa:10576/41172 |
| publishDate | 2021 |
| publisher.none.fl_str_mv | Elsevier |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| spelling | Metformin attenuates V-domain Ig suppressor of T-cell activation through the aryl hydrocarbon receptor pathway in Melanoma: In Vivo and In Vitro StudiesFawaz E., AlanaziAs Sobeai, Homood M.Alhazzani, KhalidAl-Dhfyan, AbdullahAlshammari, Musaad AAlotaibi, MoureqAl-hosaini, KhaledKorashy, Hesham M.Alhoshani, AliVISTAAHRCYP1A1IDO1MetforminCHL-1B16MelanomaMelanoma is an aggressive skin cancer with a high rate of metastasis to other organs. Recent studies specified the overexpression of V-domain Ig suppressor of T-cell activation (VISTA) and Aryl Hydrocarbon Receptor (AHR) in melanoma. Metformin shows anti-tumor activities in several cancer types. However, the mechanism is unclear. This study aims to investigate the inhibitory effect of metformin on VISTA via AHR in melanoma cells (CHL-1, B16) and animal models. VISTA and AHR levels were assessed by qPCR, Western blot, immunofluorescence microscope, flow cytometry, and immunohistochemistry. Here, metformin significantly decreased VISTA and AHR levels in vitro and in vivo. Furthermore, metformin inhibited all AHR-regulated genes. VISTA levels were dramatically inhibited by AHR modulations using shRNA and αNF, confirming the central role of AHR in VISTA. Finally, melanoma cells were xenografted in C57BL/6 and nude mice. Metformin significantly reduced the tumor volume and growth rate. Likewise, VISTA and AHR-regulated protein levels were suppressed in both models. These findings demonstrate for the first time that VISTA is suppressed by metformin and identified a new regulatory mechanism through AHR. The data suggest that metformin could be a new potential therapeutic strategy to treat melanoma patients combined with targeted immune checkpoint inhibitors.Funded by the initiative of DSR Graduate Students Research Support (GSR) - Deanship of scientific research in King Saud UniversityElsevier2023-03-20T06:35:53Z2021-12-31Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1016/j.jsps.2021.12.014Alanazi, F. E., Sobeai, H. M. A., Alhazzani, K., Al-Dhfyan, A., Alshammari, M. A., Alotaibi, M., ... & Alhoshani, A. (2022). Metformin attenuates V-domain Ig suppressor of T-cell activation through the aryl hydrocarbon receptor pathway in Melanoma: In Vivo and In Vitro Studies. Saudi Pharmaceutical Journal, 30(2), 138-149.1319-0164https://www.sciencedirect.com/science/article/pii/S1319016421002632http://hdl.handle.net/10576/41172138-149230enhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:qspace.qu.edu.qa:10576/411722024-07-23T13:52:46Z |
| spellingShingle | Metformin attenuates V-domain Ig suppressor of T-cell activation through the aryl hydrocarbon receptor pathway in Melanoma: In Vivo and In Vitro Studies Fawaz E., Alanazi VISTA AHR CYP1A1 IDO1 Metformin CHL-1 B16 Melanoma |
| status_str | publishedVersion |
| title | Metformin attenuates V-domain Ig suppressor of T-cell activation through the aryl hydrocarbon receptor pathway in Melanoma: In Vivo and In Vitro Studies |
| title_full | Metformin attenuates V-domain Ig suppressor of T-cell activation through the aryl hydrocarbon receptor pathway in Melanoma: In Vivo and In Vitro Studies |
| title_fullStr | Metformin attenuates V-domain Ig suppressor of T-cell activation through the aryl hydrocarbon receptor pathway in Melanoma: In Vivo and In Vitro Studies |
| title_full_unstemmed | Metformin attenuates V-domain Ig suppressor of T-cell activation through the aryl hydrocarbon receptor pathway in Melanoma: In Vivo and In Vitro Studies |
| title_short | Metformin attenuates V-domain Ig suppressor of T-cell activation through the aryl hydrocarbon receptor pathway in Melanoma: In Vivo and In Vitro Studies |
| title_sort | Metformin attenuates V-domain Ig suppressor of T-cell activation through the aryl hydrocarbon receptor pathway in Melanoma: In Vivo and In Vitro Studies |
| topic | VISTA AHR CYP1A1 IDO1 Metformin CHL-1 B16 Melanoma |
| url | http://dx.doi.org/10.1016/j.jsps.2021.12.014 https://www.sciencedirect.com/science/article/pii/S1319016421002632 http://hdl.handle.net/10576/41172 |