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

Document Type : Original Article

Authors

1 Department of Orthopedics and Traumatology, Hanzhong Hospital of TCM, Shaanxi, China

2 Department of Orthopedics, Hanzhong Central Hospital, Hantai District, Hanzhong, Shaanxi, Chinaal

3 Department of Orthopedics, Hanzhong Central Hospital, Hantai District, Hanzhong, Shaanxi, China

Abstract

Objective: Osteosarcoma (OS) is an uncommon sarcoma with osteoid formation in conjunction with malignant
mesenchymal cells on histological examination. SP-8356 has been reported to exhibit anti-cancer properties in human
cancers. However the impact of SP-8356 on OS is largely unknown. The metabolic pathways are coordinated by AMPactivated
protein 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 24
hours and analysed for cellular proliferation using MTT assay. DNA fragmentation was studied using ELISA based
kit. Furthermore, transwell chambers assay was used to determine cell migration and cell invasion. Targeted protein
expression levels were assessed using western blotting. For in vivo studies, mice (5-6 weeks old) were implanted with
either 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-8356
treatment significantly restricted migration and invasion of Saos-2 and MG63 cells. Compared to the control, SP-8356
significantly reduced apoptotic cell death, while it increased PGC-1α and TFAM expressions. Without affecting body
weight, 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 OS
tumor growth. Furthermore, SP-8356 was found to act through PGC-1α/TFAM and AMPK activations. SP-8356 can be
therefore used as therapeutic agent for OS treatment.

Keywords

References

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