IKKα inibition by a glucosamine derivative enhances Maspin expression in osteosarcoma cell line

Chronic inflammation has been associated to cancer development by the alteration of several inflammatory pathways, such as Nuclear Factor-kappa B pathway. In particular, I kappa B kinase alpha (IKK alpha), one of two catalytic subunit of IKK complex, has been described to be associated to cancer progression and metastasis in a number of cancers. The molecular mechanism by which IKK alpha affects cancer progression is not yet completely clarified, anyway an association between IKK alpha and the expression of Maspin (Mammary Serine Protease Inhibitor or SerpinB5), a tumor suppressor protein, has been described. IKK alpha shuttles between cytoplasm and nucleus, and when is localized into the nuclei, IKK alpha regulates the expression of several genes, among them Maspin gene, whose expression is repressed by high amount of nuclear IKK alpha. Considering that high levels of Maspin have been associated with reduced metastatic progression, it could be hypothesized that the repression of IKK alpha nuclear translocation could be associated with the repression of metastatic phenotype. The present study is aimed to explore the ability of a glucosamine derivative, 2-(N-Carbobenzyloxy) L-phenylalanylamido-2-deoxy-beta-D-glucose (NCPA), synthesized in our laboratory, to stimulate the production of Maspin in an osteosarcoma cell line, 143B. Immunofluorescence and Western blotting experiments showed that NCPA is able to inhibit IKKa nuclear translocation, and to stimulate Maspin production. Moreover, in association with stimulation of Maspin production we found the decrease of beta 1 Integrin expression, the down-regulation of metalloproteases MMP-9 and MMP-13 production and cell migration inhibition. Taking in account that beta 1 Integrin and MMP-9 and -13 have been correlated with the invasiveness of osteosarcoma, considering that NCPA affects the invasiveness of 143B cell line, we suggest that this molecule could affect the osteosarcoma metastatic ability. (C) 2016 Elsevier Ireland Ltd. All rights reserved.