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Pharmacol Res. 2006 Sep;54(3):186-94. Epub 2006 Apr 30.

In vitro anti-tumor activity of isorhamnetin isolated from Hippophae rhamnoides L. against BEL-7402 cells.

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State Key Laboratory of Bioreactor Engineering, New World Institute of Biotechnology, East China University of Science and Technology, Shanghai 200237, PR China.


Isorhamnetin, a flavonol aglycone, isolated from the traditional Chinese medicine Hippophae rhamnoides L., was investigated in its cytotoxicity and its influence on human hepatocellular carcinoma cells (BEL-7402). The cytotoxic effects of isorhamnetin showed dose- and time-dependency against BEL-7402 cells, with IC(50) equal to 74.4+/-1.13 microg ml(-1) after treatment with isorhamnetin for 72 h. Cytotoxicity of the flavonols on tumor cells depends on cellular accumulation of the drugs. The amount of isorhamnetin accumulated in BEL-7402 cells was assayed by high-performance liquid chromatography (HPLC) and showed that isorhamnetin could permeate the cell membrane into the cell. Staining with Hoechst 33258 showed fragmentation and condensation of chromatin in the cell treated with 50 microg ml(-1) isorhamnetin for 48 h. Flow cytometric analysis was performed to determine hypodiploid cells. The results of flow cytometry assay indicated that the percentage of hypodiploid BEL-7402 cells were 13.77+/-1.05% after 48 h treatment with 50 microg ml(-1) isorhamnetin. The treatment resulted in the appearance of a hypodiploid peak (sub-G(0)/G(1) peak), probably due to the presence of cells in apoptosis and apoptotic bodies with DNA content less than 2n. To our knowledge, this is the first report against human hepatocellular carcinoma cells (BEL-7402) of isorhamnetin.

[Indexed for MEDLINE]

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