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        Isocryptotanshinone Induced Apoptosis and Activated MAPK Signaling in Human Breast Cancer MCF-7 Cells

        Xuenong Zhang,Weiwei Luo,Wenwen Zhao,Jinjian Lu,Xiuping Chen 한국유방암학회 2015 Journal of breast cancer Vol.18 No.2

        Purpose: Isocryptotanshinone (ICTS) is a natural bioactive product that is isolated from the roots of the widely used medical herb Salvia miltiorrhiza. However, few reports exist on the mechanisms underlying the therapeutic effects of ICTS. Here, we report that ICTS has anticancer activity and describe the mechanism underlying this effect. Methods: The antiproliferative effect of ICTS was determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5- diphenyl-2-H-tetrazolium bromide (MTT) and clonogenic assays. The effect of ICTS on the cell cycle was measured using flow cytometry. Apoptosis was determined by Hoechst 33342 staining, DNA fragmentation assays, and Western blotting for apoptotic proteins. Finally, the effect of ICTS on mitogen-activated protein kinases (MAPKs) was determined by Western blotting. Results: ICTS significantly inhibited proliferation of MCF-7 and MDA-MB-231 human breast cancer cells, HepG2 human liver cancer cells, and A549 human lung cancer cells in vitro. Among the tested cell lines, MCF-7 cells showed the highest sensitivity to ICTS. ICTS significantly inhibited colony formation by MCF-7 cells. Furthermore, exposure of MCF-7 cells to ICTS induced cell cycle arrest at the G1 phase and decreased mitochondrial membrane potential. Hoechst 33342 staining and Western blot analysis for apoptotic proteins suggested that ICTS induced apoptosis in MCF-7 cells. In addition, ICTS activated MAPK signaling in MCF-7 cells by inducing time- and concentration-dependent phosphorylation of JNK, ERK, and p38 MAPK. Conclusion: Our results suggest that ICTS inhibited MCF-7 cell proliferation by inducing apoptosis and activating MAPK signaling pathways.

      • PTP1B Inhibitory Effect of Abietane Diterpenes Isolated from <i>Salvia miltiorrhiza</i>

        Han, Yu Mi,Oh, Hyuncheol,Na, MinKyun,Kim, Beom Seok,Oh, Won Keun,Kim, Bo Yeon,Jeong, Dae Gwin,Ryu, Seong Eon,Sok, Dai-Eun,Ahn, Jong Seog Pharmaceutical Society of Japan 2005 BIOLOGICAL & PHARMACEUTICAL BULLETIN Vol.28 No.9

        <P>Protein tyrosine phosphatase 1B (PTP1B) acts as a negative regulator of insulin signaling, and selective inhibition of PTP1B has served as a potential drug target for the treatment of type 2 diabetes. In the course of screening for PTP1B inhibitory natural products, the MeOH extract of the dried root of <I>Salvia miltiorrhiza</I> B<SMALL>UNGE</SMALL> (Labiatae) was found to exhibit significant inhibitory effect. Bioassay-guided fractionation and purification afforded three related abietane-type diterpene metabolites 1—3. Compounds 1—3 were identified as isotanshinone IIA (1), dihydroisotanshinone I (2), and isocryptotanshinone (3) mainly by analysis of NMR and MS data. Compounds 1—3 non-competitively inhibited PTP1B activity with 50% inhibitory concentration values of 11.4±0.6 μ<SMALL>M</SMALL>, 22.4±0.6 μ<SMALL>M</SMALL> and 56.1±6.3 μ<SMALL>M</SMALL>, respectively.</P>

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