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Molecules 2012, 17(1), 598-612; doi:10.3390/molecules17010598
Article

Daphnoretin Induces Cell Cycle Arrest and Apoptosis in Human Osteosarcoma (HOS) Cells

*  and
Department of Orthopaedics, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
* Author to whom correspondence should be addressed.
Received: 23 November 2011 / Revised: 29 December 2011 / Accepted: 30 December 2011 / Published: 9 January 2012
(This article belongs to the Section Natural Products)
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Abstract

In this study antiproliferation, cell cycle arrest and apoptosis induced by daphnoretin in human osteosarcoma (HOS) cells were investigated. Antiproliferative activity was measured with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The IC50 value of daphnoretin was 3.89 μM after 72 h treatment. Induction of apoptosis was evidenced by apoptotic body appearance and Annexin V-FITC/PI apoptosis detection kit. Flow cytometric analysis indicated daphnoretin arrested the cell cycle in the G2/M phase. Western-blot assay showed that the G2/M phase arrest was accompanied by down-regulation of cdc2, cyclin A and cyclin B1. Moreover, daphnoretin inhibited Bcl-2 expression and induced Bax expression to desintegrate the outer mitochondrial membrane and causing cytochrome c release. Mitochondrial cytochrome c release was associated with the activation of caspase-9 and caspase-3 cascade. Our results demonstrated that daphnoretin caused death of HOS cells by blocking cells successively in G2/M phases and activating the caspase-3 pathway.
Keywords: daphnoretin; HOS; antiproliferative; cell cycle arrest; apoptosis daphnoretin; HOS; antiproliferative; cell cycle arrest; apoptosis
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Gu, S.; He, J. Daphnoretin Induces Cell Cycle Arrest and Apoptosis in Human Osteosarcoma (HOS) Cells. Molecules 2012, 17, 598-612.

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