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The mitogen-stimulated serine/threonine kinase p70S6k plays an important role in the progression of cells from G0/G1 to S phase of the cell cycle by translational up-regulation of a family of mRNA transcripts family of mRNA transcripts which contain polypyrimidine tract at their 5 transcriptional start site. Here, we report that p70S6k was constitutively phosphorylated and activated to various degrees in serum-deprived AGS, A2058, HT-1376, MG63, MCF7, MDA-MB-435S, MDA-MB-231 and MB-157. Rapamycin treatment induced a significant dephosphorylation and inactivation of p70S6k in all cancer cell lines, while wortmannin, a specific inhibitor of PI3-K, caused a mild dephosphorylation of p70S6k in AGS, MDA-MB-435S and MB-157. In addition, SQ20006, methylxanthine phosphodiesterase inhibitor, reduced the phosphorylation of p70S6k in all cancer cells tested. Consistent with inhibitory effect of rapamycin on p70S6k activity, rapamycin inhibited [3H]-thymidine incorporation and increased the number of cells at G0/G1 phase. Furthermore, these inhibitory effects were accompanied by the decrease in growth of cancer cells. Taken together, the results indicate that the antiproliferative activity of rapamycin might be attributed to cell cycle arrest at G0/G1 phase in human cancer cells through the inhibition of constitutively activated p70S6k of cancer cells and suggest p70S6k as a potential target for therapeutic strategies aimed at preventing or inhibiting tumor growth.

SHINBARO is a purified extract from a mixture of 6 oriental herbs (Ledebouriellae Radix, Achyranthis Radix, Acanthopanacis Cortex, Cibotii Rhizoma, Glycine Semen, and Eucommiae Cortex) that have been used as a traditional medicine for treatment of several inflammatory diseases and bone disorders. We determined antiinflammatory and antinociceptive activities of SHINBARO in adjuvant-induced (osteo)arthritis in rats. This potential anti-(osteo)arthritic property of SHINBARO can be due to the downregulation of inflammatory mediators such as iNOS, COX-2, and TNF-α, the increase of pain threshold in the peripheral system, the activation of alkaline phosphatase in osteoblasts, the suppression of proteoglycan degradation, and the inhibition of MMP-2 and MMP-9 activities as demonstrated by in vitro and in vivo experimental studies. We confirmed that SHINBARO is as effective as celecoxib, a selective COX-2 inhibitor, but it has the better safety profile in clinical trials. Finally, SHINBARO was approved as a New Herbal Medicine for treatment of osteoarthritis by Korean FDA on January 25(th), 2011.

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