Negative growth control of osteosarcoma cell by Bowman-Birk protease inhibitor from soybean; involvement of connexin 43.
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.
Saito
Teruyoshi
T
Project for Complementary Factors, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8636, Japan.
Sato
Hiromi
H
Virgona
Nantiga
N
Hagiwara
Hiromi
H
Kashiwagi
Korehito
K
Suzuki
Kazuyuki
K
Asano
Ryuji
R
Yano
Tomohiro
T
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D012516:Osteosarcoma / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology*; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000494:pharmacology*; D015854:Up-Regulation
D000970:Antineoplastic Agents; D018031:Connexin 43; D011480:Protease Inhibitors; D014358:Trypsin Inhibitor, Bowman-Birk Soybean