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Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Anti-tumor effects of dihydroartemisinin on human osteosarcoma
Ye Ji1, Yi-Cai Zhang, Liu-Bao Pei
1Department of Orthopaedic Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23, Youzheng St., Nangang District, Harbin, Heilongjiang 150001, China.
Abstract:
Dihydroartemisinin (DHA) exhibits antitumor activity against a wide spectrum of cancer cells. However, whether DHA has anti-tumor effect on human osteosarcoma cells remains unknown. This study aims to investigate the anti-tumor activity of DHA and the underlying mechanisms in human osteosarcoma cell lines with different p53 mutation statuses. Four human osteosarcoma cell lines were treated with different concentrations of DHA. Then, cell proliferation was determined by the CCK-8 viability assay; apoptosis and cell cycle progression were evaluated by flow cytometry; protein expression was analyzed by western blot assay; and NF-kB activity was examined by luciferase assay. The results demonstrated that DHA treatment could inhibit the proliferation of four osteosarcoma cell lines in a dose-dependent manner. P53 wild-type osteosarcoma cells were more sensitive to DHA. Moreover, the percentage of apoptotic cell and cell arrest in G₂/M phase was increased upon DHA treatment in a dose-dependent manner. Mechanistically, DHA activated caspase-3, caspase-8, and caspase-9; upregulated the expression of Bax, FAS, and cyclin D1; downregulated the expression of Bcl-2, Cdc25B, and cyclin B1; and inhibited the activity of NF-кB. In conclusion, DHA has significant anticancer effects against human osteosarcoma cells, which include induction of apoptosis and cell cycle arrest. The p53 gene may play a certain role in the DHA-induced human osteosarcoma apoptosis and cell cycle arrest. DHA is a novel anti-osteosarcoma drug candidate that merits further study.
Insights
Dihydroartemisinin (DHA) effectively inhibits human osteosarcoma cell proliferation and induces apoptosis and cell cycle arrest. The p53 gene influences DHA
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Osteosarcoma is a primary bone cancer with limited treatment options.
- Dihydroartemisinin (DHA), a derivative of artemisinin, shows broad-spectrum antitumor activity.
- The anti-osteosarcoma effects and mechanisms of DHA, particularly concerning p53 status, are not well understood.
Purpose of the Study:
- To investigate the anti-tumor activity of DHA in human osteosarcoma cell lines.
- To elucidate the underlying molecular mechanisms of DHA's action.
- To explore the role of p53 mutation status in mediating DHA's effects.
Main Methods:
- Cell proliferation was assessed using the CCK-8 viability assay.
- Apoptosis and cell cycle progression were analyzed via flow cytometry.
- Protein expression and NF-κB activity were evaluated using Western blot and luciferase assays, respectively.
Main Results:
- DHA significantly inhibited osteosarcoma cell proliferation in a dose-dependent manner.
- Osteosarcoma cells with wild-type p53 exhibited greater sensitivity to DHA.
- DHA induced apoptosis, G₂/M cell cycle arrest, and modulated key proteins involved in apoptosis and cell cycle regulation, while inhibiting NF-κB activity.
Conclusions:
- DHA demonstrates potent anti-osteosarcoma effects by inducing apoptosis and cell cycle arrest.
- The p53 gene status appears to play a role in DHA's efficacy against osteosarcoma.
- DHA represents a promising therapeutic candidate for osteosarcoma, warranting further investigation.
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