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Catalpol suppresses osteosarcoma cell proliferation through blocking epithelial-mesenchymal transition (EMT) and
1Department of Orthopedics, The Affiliated Huai'an Hospital of Xuzhou Medical University, Jiangsu 223300, China.
Abstract:
Catalpol, an iridoid glucoside compound, is reported to possess diverse pharmacological actions. However, its effects on osteosarcoma are little to be known. In the present study, we showed that catalpol could strongly suppress osteosarcoma progression. Catalpol dose-dependently reduced the cancer cell viability. The migration of osteosarcoma cells was also consistently suppressed by catalpol treatment using the wound healing and transwell migration analysis. Catalpol reduced the expressions of Kras, receptor for activated C-kinase 1(RACK1) and matrix metalloproteinase (MMP)-2 in a dose-dependent manner, revealing the blockage of migration. Moreover, both intrinsic and extrinsic apoptosis were triggered by catalpol, as evidenced by improved cleaved Caspase-8/-9/-3 and Poly-(ADP-ribose) polymerase (PARP). Release of Cyto-c in cytoplasm and Bax up-regulation in total cells were observed in catalpol-treated cells, while mitochondrial Cyto-c and cellular Bcl-2 were down-regulated by catalpol. Reactive oxygen species (ROS) production was also involved in catalpol-induced cell death. Further, ROS scavenger, N-acetylcysteine (NAC), impeded catalpol-caused apoptosis. And suppression of signal transducer and activator of transcription 3/Janus kinase 2 gene/Src (STAT3/JAK2/Src) was involved in catalpol-induced cell death. In vivo, catalpol showed effective ability to reduce the tumor growth. Our results illustrated that catalpol might be considered as a promising pharmacological agent to suppress osteosarcoma.
Insights
Catalpol significantly suppresses osteosarcoma progression by reducing cell viability and migration. This iridoid glucoside compound induces apoptosis and inhibits tumor growth, showing potential as an anti-osteosarcoma agent.
Area of Science:
- Pharmacology
- Oncology
- Biochemistry
Background:
- Osteosarcoma is a primary bone malignancy with limited treatment options.
- Catalpol, an iridoid glucoside, exhibits various pharmacological effects but its role in osteosarcoma is largely unexplored.
Purpose of the Study:
- To investigate the anti-osteosarcoma effects of catalpol.
- To elucidate the underlying molecular mechanisms of catalpol's action against osteosarcoma cells.
Main Methods:
- In vitro studies: cell viability assays, wound healing, transwell migration assays, Western blotting, apoptosis assays (measuring cleaved Caspase-3/9/8, PARP, Cyto-c, Bax, Bcl-2), reactive oxygen species (ROS) detection.
- In vivo studies: tumor growth inhibition in animal models.
Main Results:
- Catalpol dose-dependently reduced osteosarcoma cell viability and migration.
- Catalpol suppressed key proteins involved in migration (Kras, RACK1, MMP-2).
- Catalpol induced both intrinsic and extrinsic apoptosis via mitochondrial pathways and ROS generation, involving the STAT3/JAK2/Src pathway.
- Catalpol significantly inhibited tumor growth in vivo.
Conclusions:
- Catalpol demonstrates potent anti-osteosarcoma activity both in vitro and in vivo.
- Catalpol exerts its effects by inhibiting cell proliferation, migration, and inducing apoptosis.
- Catalpol represents a promising therapeutic candidate for osteosarcoma treatment.