Negative growth control of osteosarcoma cell by Bowman-Birk protease inhibitor from soybean; involvement of connexin 43.
Negative growth control of osteosarcoma cell by Bowman-Birk protease inhibitor from soybean; involvement of connexin 43.
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DOI：
10.1016/j.canlet.2007.01.021
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发表时间：
2007-08
期刊：
影响因子：
9.7
通讯作者：
Teruyoshi Saito;Hiromi Sato;N. Virgona;H. Hagiwara;K. Kashiwagi;Kazuyuki Suzuki;R. Asano;T. Yano
中科院分区：
文献类型：
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作者：
Teruyoshi Saito;Hiromi Sato;N. Virgona;H. Hagiwara;K. Kashiwagi;Kazuyuki Suzuki;R. Asano;T. Yano
大豆蛋白酶抑制剂（Bowman-Birk protease inhibitor，BBI）是一种潜在的肿瘤化学预防剂。然而，其机制尚不清楚。本研究旨在探讨BBI依赖的人骨肉瘤细胞（U2 OS细胞）负性生长调控机制。BBI通过诱导连接蛋白（Cx）43（U2 OS细胞中的肿瘤抑制基因）对细胞进行负生长控制。在通过Cx43反义核苷酸处理诱导的Cx43下调下，BBI的这种负生长控制被废除。BBI依赖性诱导Cx43的表达是由于Cx43 mRNA的升高和Cx43蛋白的稳定。特别是，BBI依赖性抑制蛋白酶体中的糜蛋白酶样活性有助于Cx43蛋白的稳定。这些结果表明BBI的主要负生长效应是基于U2 OS细胞中Cx43表达的恢复。
Bowman–Birk protease inhibitor (BBI) from soybean acts as a potential chemopreventive agent in several types of tumors. However, the mechanism is still unclear. The present study was undertaken to estimate a mechanism of BBI-dependent negative growth control of human osteosarcoma cell (U2OS cell). BBI had negative growth control of the cells via induction of connexin (Cx) 43, a tumor suppressor gene in U2OS cells. This negative growth control by BBI was abrogated under down-regulation of Cx43 induced by a Cx43 antisense nucleotide treatment. It was also found that the BBI-dependent induction of Cx43 was due to elevation of Cx43 mRNA and stabilization of Cx43 protein. Especially, BBI-dependent inhibition of chymotrypsin-like activity in proteasome contributed to stabilization of Cx43 protein. These results suggest that a major negative growth effect of BBI is based on the restoration of Cx43 expression in U2OS cells.