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Cepharanthine enhances in vitro and in vivo thermosensitivity of a mouse fibrosarcoma, FSa-II, based on increased apoptosis

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Cepharanthine (Ce) is a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata. In our previous study, Ce significantly enhanced thermosensitivity and thereby reduced thermotolerance in vitro, and intra-peritoneal injection of Ce slightly enhanced thermosensitivity in vivo. In the present study, we investigated Ce's effect in vitro on the pattern of cell death after heating and the effect of intra-tumoral injection of Ce on in vivo thermosensitivity using a mouse fibrosarcoma, FSa-II, and C3H/He mice. Ce significantly enhanced the in vitro thermosensitivity of FSa-II cells with heating at 44°C, with increased Ce concentration. Time-lapse microscopic observation of individual cells confirmed that Ce treatment hastened both apoptosis (specifically, apoptotic budding) and necrosis (as indicated by staining with propidium iodide). Staining with annexin V-enhanced green fluorescent protein indicated that Ce used concomitantly with heating significantly increased the proportion of cells in the early stage of apoptosis. Ce combined with heating also significantly increased the proportion of cells with high intracellular caspase-3 activity, as detected by a substrate of caspase-3, PhiPhiLux-G1D2. The intra-tumoral injection of Ce, followed by heating at 44°C, significantly delayed in vivo tumor growth, and this delay increased in a Ce concentration-dependent manner. Ce injected 30 min before heating delayed tumor growth more than Ce injected immediately before heating. These findings suggest the potential of Ce as a thermosensitizer to increase apoptosis of tumor cells.
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Document Type: Research Article

Affiliations: Department of Radiology, Okayama University Medical School, Okayama 700-8558, Japan

Publication date: March 1, 2004

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  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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