Beta-hydroxyisovalerylshikonin induces apoptosis and G0/G1 cell-cycle arrest of endometriotic stromal cells: a preliminary in vitro study

Masakazu Nishida, Nishida M, M. Nishida, Nasu K, Kaei Nasu, K Nasu, T. Ueda, Ueda T, Tami Ueda, Yuge A, A Yuge, Akitoshi Yuge, N Takai, Takai N, Noriyuki Takai, Narahara H, H Narahara, Hisashi Narahara
Human Reproduction · 2006 · vol. 21(11) , pp. 2850–2856 · doi:10.1093/humrep/del270 · PMID:16877374 · W2108669572
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Beta-hydroxyisovalerylshikonin inhibited endometriotic stromal cell proliferation and DNA synthesis, inducing apoptosis and G0/G1 cell-cycle arrest via caspase activation and Bcl-2 down-regulation.

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Abstract

BACKGROUND: Most of the current medical treatments for endometriosis aim to down-regulate the estrogen activity. However, a high recurrence rate after medical treatments has been the most significant problem. Beta-hydroxyisovalerylshikonin (beta-HIVS) is an ATP non-competitive inhibitor of protein-tyrosine kinases and is considered an apoptosis-inducing agent. The aim of this study is to evaluate the effects of beta-HIVS on the proliferation, cell cycle and apoptosis of endometriotic stromal cells. METHODS: We investigated the effects of beta-HIVS on cultured ovarian endometriotic cyst stromal cells (ECSC) by a modified methylthiazoletetrazolium (MTT) assay, a 5-bromo-2'-deoxyuridine (BrdU) incorporation assay and internucleosomal DNA fragmentation assays. The effect of beta-HIVS on the cell cycle of ECSC was determined by flow cytometry. The expression of apoptosis-related molecules was examined in ECSC using western blot analysis. RESULTS: Beta-HIVS significantly inhibited the proliferation and DNA synthesis of ECSC and induced apoptosis and G0/G1 phase cell-cycle arrest of these cells. Down-regulation of the B-cell lymphoma/leukaemia-2 (Bcl-2) expression with the activation of caspase-3, caspase-8 and caspase-9 was observed in ECSC after beta-HIVS treatment. CONCLUSIONS: These results suggest that beta-HIVS induces apoptosis of ECSC by suppressing anti-apoptotic proteins. Although our present findings are preliminary, beta-HIVS could potentially be a therapeutic agent for the treatment of endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Apoptosis Cell Cycle Endometriosis Naphthoquinones Stromal Cells Apoptosis Apoptosis Bromodeoxyuridine Bromodeoxyuridine Cell Cycle Cell Cycle Cell Division Cell Division Cell Division Cell Survival Cell Survival Cell Survival DNA Fragmentation DNA Fragmentation Endometriosis

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