Abstract
Inhibition of proliferating cells is a critical strategy for cancer therapy. In this study, we demonstrated that coronarin D, a natural component extracted from the rhizomes of Hedychium coronarium, significantly suppressed the proliferation of osteosarcoma cells. The treatment with coronarin D resulted in the activation of caspase-3 and apoptosis. This treatment induced the accumulation of cyclin B1 and DNA condensation indicating the treated osteosarcoma cells were arrested in mitotic phase. Furthermore, the treatment with coronarin D increased the levels of phosphorylated c-Jun NH2-terminal kinase (JNK) in human osteosarcoma cells. Pretreatment with JNK inhibitor blocked the accumulation of cyclin B1 and DNA condensation, resulting the accumulation of tetraploid cells in coronarin D-treated osteosarcoma HOS cells, indicating JNK inactivation blocked the mitotic entry and arrested cells in the 4 N state. After adaptation, the arrested tetraploid cells continued to duplicate their DNA resulting in polyploidy. Interestingly, when the arrested mitotic cells induced by coronarin D were treated with JNK inhibitor, the accumulated cyclin B1 and DNA condensation were immediately eliminated. These arrested 4 N cells loss the ability to undergo cytokinesis, and ultimately continued to duplicate DNA upon prolonged arrest resulting in the production of polyploid populations. JNK inactivation, either by the pretreatment with JNK inhibitor or the treatment with JNK inhibitor in coronarin D-induced mitotic cells, both caused resistance to coronarin D-induced cell death. Taken together, our findings indicate that coronarin D induces the apoptosis and mitosis arrest in human osteosarcoma cells. JNK has a crucial role in coronarin D-induced mitosis arrest and apoptosis. We hypothesize that functional evaluation of JNK may produce more specific and effective therapies in coronarin D-related trail for treatment of human osteosarcoma.
Highlights
Osteosarcoma is the most common type of primary malignant bone tumor
Coronarin D, a natural product extracted from the rhizomes of Hedychium coronarium, has been
Coronarin D, a natural product extracted from the rhizomes of Hedychium coronarium, has been shown to possess antimicrobial and antifungal activity [6,7]
Summary
Osteosarcoma is the most common type of primary malignant bone tumor. It arises from osteoid tissue in the bone during periods of rapid growth and predominately affects adolescents and young adults. Osteosarcoma is characterized by a high propensity for metastasis Once this tumor exhibits the ability to invade, the 5-year survival rate for patients with metastatic osteosarcoma decreases dramatically to approximately 20%. It has remained virtually unchanged over the past 30 years [1,2]. Recent progress has focused activity on the chemoprevention by natural products for their antigrowth activity against cancer cells [3] These may exhibit less side effects compared to synthetic effects and apoptosis potential in cells [8].compounds. Taxol is isolated from the bark of Taxus brevifolia It is a microtubulestudy, we evaluated the potential antitumor effect of coronarin D against osteosarcoma.
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