In vitro studies on the @entity706 growth-inhibitory activity of XXXX .

@entity2227 @entity137 @entity851 @entity706 @entity462 @entity5 @entity1434 @entity6514 @entity35 @entity3378
@entity3378 (SASP) is a novel, potent inhibitor of cellular @entity1434 uptake mediated by the x(c)- @entity1434 / @entity2227 antiporter. Lymphoid cells cannot synthesize cyst(e)ine and depend for growth on its uptake from their micro-environment. We previously showed that SASP (0.2 mM) can abrogate @entity706 cell proliferation in vitro by specifically inhibiting x(c)- -mediated @entity1434 uptake. Intraperitoneal administration of SASP to Noble @entity35 markedly suppressed Nb2-U17 @entity35 @entity706 transplant growth, notably without major @entity137 to the hosts. Since Nb2-U17 cells are x(c)- -deficient, the @entity851 was apparently not due to SASP- @entity5 cell interaction, but possibly to interference with x(c)- -mediated @entity462 secretion by somatic cells. In this study we found that replication of x(c)- -deficient Nb2-11 @entity706 cells can be sustained in vitro, in the absence of @entity1434 uptake enhancers, by co-culturing with IMR-90 fibroblasts known to secrete @entity462 . SASP, at 0.15 and 0.2 mM, arrested replication of fibroblast-driven Nb2-11 cells by 93 and 100%, respectively, without impeding fibroblast proliferation. Addition of @entity6514 (60 microM), a @entity1434 uptake enhancer, almost completely prevented this @entity851 , indicating that SASP specifically inhibited @entity462 secretion by the fibroblasts, a process based on x(c)- -mediated @entity1434 uptake. It is proposed that the @entity706 growth-inhibitory activity of SASP in vivo involves inhibition of @entity462 secretion by @entity5 -associated somatic cells (macrophages, dendritic cells), leading to @entity462 starvation of the @entity5 cells and apoptosis. The difference between the @entity706 cells and fibroblasts in sensitivity to SASP treatment is consistent with the marked antitumor effect of SASP lacking significant side effects.
