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Cardiac glycosides, known as inhibitors of Na.sup.+,K.sup.+-ATPase, have anti-cancer effects such as suppression of cancer cell proliferation and induction of cancer cell death. Here, we examined the signaling pathway elicited by cardiac glycosides in the human hepatocellular carcinoma HepG2 cells and human epidermoid carcinoma KB cells. Three kinds of cardiac glycosides (ouabain, oleandrin, and digoxin) inhibited the cancer cell proliferation and decreased the expression level of thyroid adenoma-associated protein (THADA). Interestingly, the knockdown of THADA inhibited cancer cell proliferation, and the proliferation was significantly rescued by re-expression of THADA in the THADA-knockdown cells. In addition, the THADA-knockdown markedly decreased the expression level of L-type amino acid transporter LAT1. Cardiac glycosides also reduced the LAT1 expression. The LAT1 inhibitor, JPH203, significantly weakened the cancer cell proliferation. These results suggest that the binding of cardiac glycosides to Na.sup.+,K.sup.+-ATPase negatively regulates the THADA-LAT1 pathway, exerting the anti-proliferative effect in cancer cells. Keywords: Thyroid adenoma-associated protein, L-type amino acid transporter 1, Na.sup.+,K.sup.+-ATPase, Cardiac glycoside, Cancer cells, Author(s): Mizuki Katoh[sup.1], Takuto Fujii[sup.1], Yoshiaki Tabuchi[sup.2], Takahiro Shimizu[sup.1] and Hideki Sakai[sup.1] Background The gene of Thyroid adenoma associated (THADA) was identified as a target gene affected by chromosome 2p21 [...]

In SmB 6 , the prototypical material of valence fluctuations and Kondo semiconductors, there remain several unsolved problems in the bulk properties at low temperatures. We have studied a single crystalline sample of SmB 6 by 11 B-nuclear magnetic resonance (NMR) measurements with the precise control of the field direction in the 1 ¯ 10 plane. The temperature dependence of the nuclear quadrupole frequency ν Q and the full width at half maximum (FWHM), estimated from obtained spectra indicates that there are two distinct low-temperature regions in SmB 6 : the first is the region down to approximately 10 K, where a decrease in the FWHM and an increase in ν Q with lowering temperature are understood in the framework of the evolution of the hybridization effects between 4f and conduction electrons accompanied with an intermediate valence state. Below 10 K, the second region, ν Q and the FWHM undergo a sharp change in their temperature dependence. Through both electrical and magnetic interactions, the present results suggest that the low-temperature state below 10 K is dominated by additional physical properties other than the hybridization and the valence fluctuations. [ABSTRACT FROM AUTHOR]