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- 2015.1
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Scoparone, which is a major constituent of Artemisia capillaries, has been identified as an anticoagulant, hypolipidemic, vasorelaxant, anti-oxidant and anti-inflammatory drug, and it is used for the traditional treatment of neonatal jaundice. Therefore, we hypothesized that scoparone could suppress the proliferation of VSMCs by interfering with STAT3 signaling. We found thatthe proliferation of these cells was significantly attenuated by scoparone in a dose-dependent manner. Scoparone markedly reduced the serum-stimulated accumulation of cells in the S phase and concomitantly increased the proportion of cells in theG0/G1 phase, which was consistent with the reduced expression of cyclin D1, phosphorylated Rb and survivin in the VSMCs. Cell adhesion markers, such as MCP-1 and ICAM-1, were significantly reduced by scoparone. Interestingly, this compound attenuated the increase in cyclin D promoter activity by inhibiting the activities of both the WT and active forms of STAT3. Similarly, the expression of a cell proliferation marker induced by PDGF was decreased by scoparone with no change in the phosphorylation of JAK2 or Src. On the basis of the immunofluorescence staining results, STAT3 proteins phosphorylated by PDGF were predominantly localized to the nucleus and were markedly reduced in the scoparone-treated cells. In summary, scoparone blocks the accumulation of STAT3 transported from the cytosol to the nucleus, leading to the suppression of VSMC proliferation through G1 phase arrest and the inhibition of Rb phosphorylation. This activity occurs independent of the form of STAT3 and upstream of kinases, such as Jak and Src, which are correlated with abnormal vascular remodeling due to the presence of an excess of growth factors following vascular injury. These data provide convincing evidence that scoparone may be a new preventative agent for the treatment of cardiovascular diseases.
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참고문헌 (24)
참고문헌 신청
Al Zaid Siddiquee K / 2008 / STAT3 as a target for inducing apoptosis in solid and hematological tumors / Cell Res 18 : 254 ~ 267
Banes AK / 2005 / Activation of the JAK/STAT pathway in vascular smooth muscle by serotonin / Am J Physiol Cell Physiol 288 : C805 ~ C812
Bromberg J / 2000 / The role of STATs in transcriptional control and their impact on cellular function / Oncogene 19 : 2468 ~ 2473
Decker T / 2000 / Serine phosphorylation of STATs / Oncogene 19 : 2628 ~ 2637
Hoult JR / 1996 / Pharmacological and biochemical actions of simple coumarins : natural products with therapeutic potential / Gen Pharmacol 27 : 713 ~ 722
Banes AK / 2005 / Activation of the JAK/STAT pathway in vascular smooth muscle by serotonin / Am J Physiol Cell Physiol 288 : C805 ~ C812
Bromberg J / 2000 / The role of STATs in transcriptional control and their impact on cellular function / Oncogene 19 : 2468 ~ 2473
Decker T / 2000 / Serine phosphorylation of STATs / Oncogene 19 : 2628 ~ 2637
Hoult JR / 1996 / Pharmacological and biochemical actions of simple coumarins : natural products with therapeutic potential / Gen Pharmacol 27 : 713 ~ 722
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