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The dried roots of Saussurea lappa are used in traditional medicine for the treatment of dysentery, nausea, and vomiting, as well as for their antiulcer, anti-inflammatory, and antitumor properties. In this study, the cytotoxic activities of the ethanol extract of Saussurea lappa root extract (SLRE) on neuroblastoma cells were investigated, wherein the effect of the plant extracts on cancer cells has not been fully clarified. Here, cytotoxicity was examined by cell viability assay, fragmented DNA by DAPI, caspase-3 activity by immunofluorescence staining, and activation of proteins was detected by western blotting. SLRE was demonstrated to reduce human SH-SY5Y and rat B103 neuroblastoma cell viability more effectively than mouse and rat fibroblast cells. However, the SLRE-treated cells exhibited morphological changes including cell rounding, cell shrinkage, neurite retraction, and membrane blebbing, which indicated the initiation of apoptosis in the SHSY5Y cells. Importantly, SLRE-induced cells displayed upregulation of the pro-apoptotic protein Bax and downregulation of the anti-apoptotic proteins Bcl-2, Bcl-xl, and Mcl-1, which suggest the mitochondia-mediated apoptotic pathway. In addition, SLRE activated cleaved caspases-9 and -3, also indicating the intrinsic caspase-mediated apoptosis pathway.

Consequently, phosphatidylinositide-3-kinase/protein kinase B (AKT) and glycogen synthase kinase-3β (GSK-3) protein expression and activity were downregulated by SLRE treatment, suggesting that the growth inhibitory activity of this plant extracts is associated with these pathways. Therefore, the findings from this study demonstrated that the growth inhibitory and cytotoxic effects of SLRE on SH-SY5Y cells are accomplished through the mitochondria-mediated pathway, and that this natural extract might be useful as an anticancer agent for neuroblastoma treatment.

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참고문헌 (39건) : 자료제공( 네이버학술정보 )

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번호 참고문헌 국회도서관 소장유무
1 Bcl-2-regulated apoptosis: mechanism and therapeutic potential 네이버 미소장
2 MYCN-non-amplified metastatic neuroblastoma with good prognosis and spontaneous regression: A molecular portrait of stage 4S 네이버 미소장
3 Bouchier-Hayes L, Lartigue L, Newmeyer DD. 2005. Mitochondria: pharmacological manipulation of cell death. J Clin Invest. 115:2640–2647. 미소장
4 The activation of glycogen synthase by insulin switches from kinase inhibition to phosphatase activation during adipogenesis in 3T3-L1 cells. 네이버 미소장
5 Regulation of mitochondrial membrane permeabilization by BCL-2 family proteins and caspases 네이버 미소장
6 Mechanisms of neuroblastoma regression 네이버 미소장
7 The Apaf-1 apoptosome: a large caspase-activating complex 네이버 미소장
8 Molecular biology of neuroblastoma 네이버 미소장
9 Cecconi F, Gruss P. 2001. Apaf1 in developmental apoptosis and cancer: how many ways to die? Cell Mol Life Sci. 58: 1688–1697. 미소장
10 Active compounds from Saussurea lappa Clarks that suppress hepatitis B virus surface antigen gene expression in human hepatoma cells 네이버 미소장
11 Redox Regulation of Apoptosis before and after Cytochrome C Release 소장
12 Silibinin inhibits cell invasion through inactivation of both PI3K-Akt and MAPK signaling pathways 네이버 미소장
13 In vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa 네이버 미소장
14 The Bcl2 family: regulators of the cellular life-or-death switch 네이버 미소장
15 Ekert PG, Silke J, Vaux DL. 1999. Caspase inhibitors. Cell Death Differ. 6:1081–1086. 미소장
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17 Hong WK, Sporn MB. 1997. Recent advances in chemoprevention of cancer. Science. 278:1073–1077. 미소장
18 Chemoinhibitory effect of mulberry anthocyanins on melanoma metastasis involved in the Ras/PI3K pathway. 네이버 미소장
19 Progress in cancer chemoprevention: development of diet-derived chemopreventive agents. 네이버 미소장
20 Saussurea lappa induces G2-growth arrest and apoptosis in AGS gastric cancer cells 네이버 미소장
21 Caspase-9 네이버 미소장
22 Still embedded together binding to membranes regulates Bcl-2 protein interactions. 네이버 미소장
23 Maris JM, Hogarty MD, Bagatell R, Cohn SL. 2007. Neuroblastoma. Lancet. 369:2106–2120. 미소장
24 Mitochondria in Apoptosis: Bcl-2 Family Members and Mitochondrial Dynamics 네이버 미소장
25 Glycogen Synthase Kinase-3 Regulates Mitochondrial Outer Membrane Permeabilization and Apoptosis by Destabilization of MCL-1 네이버 미소장
26 Differential Growth Suppression of Human Melanoma Cells by Tea (Camellia sinensis) Epicatechins (ECG, EGC and EGCG) 네이버 미소장
27 EGCG inhibits growth, invasion, angiogenesis and metastasis of pancreatic cancer. 네이버 미소장
28 Chemoprevention of cancer 네이버 미소장
29 The role of BH3-only proteins in the immune system 네이버 미소장
30 Deciphering the rules of programmed cell death to improve therapy of cancer and other diseases. 네이버 미소장
31 Sun CM, Syu WJ, Don MJ, Lu JJ, Lee GH. 2003. Cytotoxic sesquiterpene lactones from the root of Saussurea lappa. J Nat Prod. 66:1175–1180. 미소장
32 Inhibitors of the Wnt/ beta -Catenin Signaling Pathway as Novel Anticancer Drugs 네이버 미소장
33 Thornberry NA, Lazebnik Y. 1998. Caspases: enemies within. Science. 281:1312–1316. 미소장
34 Essential role for protein kinase B (PKB) in insulin-induced glycogen synthase kinase 3 inactivation. Characterization of dominant-negative mutant of PKB. 네이버 미소장
35 Indigofera suffruticosa: An Alternative Anticancer Therapy 네이버 미소장
36 Wang X. 2001. The expanding role of mitochondria in apoptosis. Genes Dev. 15:2922–2933. 미소장
37 Saussureamines A, B, C, D, and E, new anti-ulcer principles from Chinese Saussureae Radix. 네이버 미소장
38 The BCL-2 protein family: opposing activities that mediate cell death 네이버 미소장
39 A review of therapeutic potential of Saussurea lappa-An endangered plant from Himalaya 네이버 미소장