SP-8356 (A Verbenone Derivative) Inhibits Proliferation, Suppresses Cell Migration and Invasion and Decreases Tumor Growth of Osteosarcoma: Role of PGC-1α/TFAM and AMPK-Activation
Objective: Osteosarcoma (OS) is an uncommon sarcoma with osteoid formation in conjunction with malignantmesenchymal cells on histological examination. SP-8356 has been reported to exhibit anti-cancer properties in humancancers. However the impact of SP-8356 on OS is largely unknown. The metabolic pa...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Royan Institute (ACECR), Tehran
2023-05-01
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| Series: | Cell Journal |
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| Online Access: | https://www.celljournal.org/article_701714_b092a21da80c44ebc15318a226994212.pdf |
| _version_ | 1797807137273937920 |
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| author | Wenning Cui Dengfeng Yang Xiaoyan Chen Hong Yu |
| author_facet | Wenning Cui Dengfeng Yang Xiaoyan Chen Hong Yu |
| author_sort | Wenning Cui |
| collection | DOAJ |
| description | Objective: Osteosarcoma (OS) is an uncommon sarcoma with osteoid formation in conjunction with malignantmesenchymal cells on histological examination. SP-8356 has been reported to exhibit anti-cancer properties in humancancers. However the impact of SP-8356 on OS is largely unknown. The metabolic pathways are coordinated by AMPactivatedprotein kinase (AMPK), which maintains a balance between the supply and demand of nutrients and energy.This study aimed to investigate effect of SP-8356 on proliferation and apoptosis of OS cells and tumor growth in mice.Furthermore, involvement of PGC-1α/TFAM and AMPK-activation was studied.Materials and Methods: In the experimental study, Saos-2 and MG63 cells were cultured with SP-8356 for 24hours and analysed for cellular proliferation using MTT assay. DNA fragmentation was studied using ELISA basedkit. Furthermore, transwell chambers assay was used to determine cell migration and cell invasion. Targeted proteinexpression levels were assessed using western blotting. For in vivo studies, mice (5-6 weeks old) were implanted witheither Saos-2 or MG63 cells on dorsal surface subcutaneously and they were administered with SP-8356 (10 mg/kg)for two weeks prior to bone tumor induction.Results: We found that SP-8356 exerted anti-proliferative effects on Saos-2 and MG63 cells. Furthermore, SP-8356treatment significantly restricted migration and invasion of Saos-2 and MG63 cells. Compared to the control, SP-8356significantly reduced apoptotic cell death, while it increased PGC-1α and TFAM expressions. Without affecting bodyweight, SP-8356 significantly reduced tumor development in mice, as compared to the control group.Conclusion: SP-8356 was found to inhibit proliferation, suppressed cells migration and invasion and decreased OStumor growth. Furthermore, SP-8356 was found to act through PGC-1α/TFAM and AMPK activations. SP-8356 can betherefore used as therapeutic agent for OS treatment. |
| first_indexed | 2024-03-13T06:18:01Z |
| format | Article |
| id | doaj.art-cb88622a8c6544e7b58eacefaf15b3ca |
| institution | Directory Open Access Journal |
| issn | 2228-5806 2228-5814 |
| language | English |
| last_indexed | 2024-03-13T06:18:01Z |
| publishDate | 2023-05-01 |
| publisher | Royan Institute (ACECR), Tehran |
| record_format | Article |
| series | Cell Journal |
| spelling | doaj.art-cb88622a8c6544e7b58eacefaf15b3ca2023-06-10T07:58:31ZengRoyan Institute (ACECR), TehranCell Journal2228-58062228-58142023-05-0125529129910.22074/cellj.2023.557404.1052701714SP-8356 (A Verbenone Derivative) Inhibits Proliferation, Suppresses Cell Migration and Invasion and Decreases Tumor Growth of Osteosarcoma: Role of PGC-1α/TFAM and AMPK-ActivationWenning Cui0Dengfeng Yang1Xiaoyan Chen2Hong Yu3Department of Orthopedics and Traumatology, Hanzhong Hospital of TCM, Shaanxi, ChinaDepartment of Orthopedics, Hanzhong Central Hospital, Hantai District, Hanzhong, Shaanxi, ChinaalDepartment of Orthopedics and Traumatology, Hanzhong Hospital of TCM, Shaanxi, ChinaDepartment of Orthopedics, Hanzhong Central Hospital, Hantai District, Hanzhong, Shaanxi, ChinaObjective: Osteosarcoma (OS) is an uncommon sarcoma with osteoid formation in conjunction with malignantmesenchymal cells on histological examination. SP-8356 has been reported to exhibit anti-cancer properties in humancancers. However the impact of SP-8356 on OS is largely unknown. The metabolic pathways are coordinated by AMPactivatedprotein kinase (AMPK), which maintains a balance between the supply and demand of nutrients and energy.This study aimed to investigate effect of SP-8356 on proliferation and apoptosis of OS cells and tumor growth in mice.Furthermore, involvement of PGC-1α/TFAM and AMPK-activation was studied.Materials and Methods: In the experimental study, Saos-2 and MG63 cells were cultured with SP-8356 for 24hours and analysed for cellular proliferation using MTT assay. DNA fragmentation was studied using ELISA basedkit. Furthermore, transwell chambers assay was used to determine cell migration and cell invasion. Targeted proteinexpression levels were assessed using western blotting. For in vivo studies, mice (5-6 weeks old) were implanted witheither Saos-2 or MG63 cells on dorsal surface subcutaneously and they were administered with SP-8356 (10 mg/kg)for two weeks prior to bone tumor induction.Results: We found that SP-8356 exerted anti-proliferative effects on Saos-2 and MG63 cells. Furthermore, SP-8356treatment significantly restricted migration and invasion of Saos-2 and MG63 cells. Compared to the control, SP-8356significantly reduced apoptotic cell death, while it increased PGC-1α and TFAM expressions. Without affecting bodyweight, SP-8356 significantly reduced tumor development in mice, as compared to the control group.Conclusion: SP-8356 was found to inhibit proliferation, suppressed cells migration and invasion and decreased OStumor growth. Furthermore, SP-8356 was found to act through PGC-1α/TFAM and AMPK activations. SP-8356 can betherefore used as therapeutic agent for OS treatment.https://www.celljournal.org/article_701714_b092a21da80c44ebc15318a226994212.pdfapoptosismiceosteosarcomasp-8356tumor growth |
| spellingShingle | Wenning Cui Dengfeng Yang Xiaoyan Chen Hong Yu SP-8356 (A Verbenone Derivative) Inhibits Proliferation, Suppresses Cell Migration and Invasion and Decreases Tumor Growth of Osteosarcoma: Role of PGC-1α/TFAM and AMPK-Activation Cell Journal apoptosis mice osteosarcoma sp-8356 tumor growth |
| title | SP-8356 (A Verbenone Derivative) Inhibits Proliferation, Suppresses Cell Migration and Invasion and Decreases Tumor Growth of Osteosarcoma: Role of PGC-1α/TFAM and AMPK-Activation |
| title_full | SP-8356 (A Verbenone Derivative) Inhibits Proliferation, Suppresses Cell Migration and Invasion and Decreases Tumor Growth of Osteosarcoma: Role of PGC-1α/TFAM and AMPK-Activation |
| title_fullStr | SP-8356 (A Verbenone Derivative) Inhibits Proliferation, Suppresses Cell Migration and Invasion and Decreases Tumor Growth of Osteosarcoma: Role of PGC-1α/TFAM and AMPK-Activation |
| title_full_unstemmed | SP-8356 (A Verbenone Derivative) Inhibits Proliferation, Suppresses Cell Migration and Invasion and Decreases Tumor Growth of Osteosarcoma: Role of PGC-1α/TFAM and AMPK-Activation |
| title_short | SP-8356 (A Verbenone Derivative) Inhibits Proliferation, Suppresses Cell Migration and Invasion and Decreases Tumor Growth of Osteosarcoma: Role of PGC-1α/TFAM and AMPK-Activation |
| title_sort | sp 8356 a verbenone derivative inhibits proliferation suppresses cell migration and invasion and decreases tumor growth of osteosarcoma role of pgc 1α tfam and ampk activation |
| topic | apoptosis mice osteosarcoma sp-8356 tumor growth |
| url | https://www.celljournal.org/article_701714_b092a21da80c44ebc15318a226994212.pdf |
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