Gambogic Acid Induced Apoptosis through Activation of Caspase-dependent Pathway in Aortic Smooth Muscle Cells

KIM, DAE-KWANG (김대광); Tae-Jin Lee (이태진); 김은애; 강주환; 김경곤; Kim， Joo Young (김주영)

doi:10.11637/aba.2013.26.3.105

Gambogic Acid Induced Apoptosis through Activation of Caspase-dependent Pathway in Aortic Smooth Muscle Cells

Anatomy & Biological Anthropology
Abbr : Anat Biol Anthropol
2013, 26(3), pp.105~114
DOI : 10.11637/aba.2013.26.3.105
Publisher : 대한체질인류학회
Research Area : Medicine and Pharmacy > Anatomy

KIM, DAE-KWANG ¹, Tae-Jin Lee ², 김은애 ², 강주환 ², 김경곤 ², Kim， Joo Young ²

¹계명대학교
²영남대학교 의과대학 해부학교실

Accredited

ABSTRACT

Gambogic acid (GA) has powerful apoptotic actions. The authors investigated whether GA has apoptotic effects on aortic smooth muscle cells, and compared its potency with that of simvastatin. Smooth muscle cells were isolated from the aortas of Sprague-Dawley rats (4-6 week). Cell purities were confirmed by IF staining using α-smooth muscle actin antibody. The IC50 values for cell death by GA and simvastatin were determined using a MTT assay, and the apoptotic effects of 1 μM GA or 30 μM simvastatin (concentrations correspond to IC50 values) were determined after 24 h of treatment using live cell images and by FITC annexin-V and propidium iodide double-staining. In addition, western blotting was used to evaluate apoptosis by quantifying reductions in the expression levels of the PARP and procaspase-3 as well as cleavages of PARP and procaspase-3after treatment with 1 μM GA or 30 μM simvastatin. The IC50 of GA (1 μM) was lower than that of simvastatin (30 μM). Cell numbers were markedly reduced by both drugs in live cell images. GA (1 μM) produced a higher level of apoptosis than 30 μM simvastatin (26.4±2.37% vs. 8.3±1.54%, respectively; P⁄0.05, n=3) by FITC annexin-V & PI double-staining. In addition, 1 μM GA reduced the expressions of PARP, procaspase-3, and Mcl-1 in cells, whereas 30 μM simvastatin did not. Pretreatment with z-VAD-fmk attenuated GA-induced apoptosis and the cleavages of PARP and procaspase-3. The decreased level of Mcl-1 protein induced by GA treatment was recovered by z-VAD-fmk. These results indicate that GA-induced apoptosis was mediated by a caspase-dependent pathway.

KEYWORDS

Gambogic acid, Apoptosis, Smooth muscle cells, Simvastatin

Citation status

* References for papers published after 2023 are currently being built.

[journal] Raines EW / 1993 / Smooth muscle cells and the pathogenesis of the lesions of atherosclerosis / Br Heart J 69 : 30~37

[journal] Ross R / 1999 / Atherosclerosis-an inflammatory disease / N Engl J Med 340 : 115~126

[journal] Libby P / 2002 / Inflammation in atherosclerosis / Nature 420 : 868~874

[journal] Hur KY / 2008 / Therapeutic effect of magnesium lithospermate B on neointimal formation after balloon-induced vascular injury / Eur J Pharmacol 586 : 226~233

[journal] Owens GK / 2004 / Molecular regulation of vascular smooth muscle cell differentiation in development and disease / Physiol Rev 84 : 767~801

[journal] Newby AC / 1996 / Proliferation, migration, matrix turnover and death of smooth muscle cells in native coronary and vein graft atherosclerosis / Curr Opin Cardiol 11 : 574~582

[journal] Thyberg J / 1997 / Phenotypic modulation of smooth muscle cells after arterial injury is associated with changes in the distribution of laminin and fibronectin / J Histochem Cytochem 45 : 837~846

[journal] Schwartz SM / 1995 / The intima. Soil for atherosclerosis and restenosis / Circ Res 77 : 445~465

[journal] Stiles CD / 1979 / Dual control of cell growth by somatomedins and platelet-derived growth factor / Proc Natl Acad Sci USA 76 : 1279~1283

[journal] Raines EW / 2004 / PDGF and cardiovascular disease / Cytokine Growth Factor Rev : 237~254

[journal] Osada-Oka M / 2008 / VEGFenhanced proliferation under hypoxia by an autocrine mechanism in human vascular smooth muscle cells / J Atheroscler Thromb 15 : 26~33

[journal] Holm PW / 2009 / Atherosclerotic plaque development and instability: a dual role for VEGF / Ann Med 41 : 257~264

[journal] Ross R / 1995 / Cell biology of atherosclerosis / Annu Rev Physiol 57 : 791~804

[journal] Ross R / 1990 / Mechanisms of atherosclerosis-a review / Adv Nephrol Necker Hosp 19 : 79~86

[journal] Blum A / 1996 / The role of inflammation in atherosclerosis / Isr J Med Sci 32 : 1059~1065

[journal] Bochaton-Piallat / 1995 / Apoptosis participates in cellularity regulation during rat aortic intimal thickening / Am J Pathol 146 : 1059~1064

[journal] Guo QL / 2006 / Inhibition of human telomerase reverse transcriptase gene expression by gambogic acid in human hepatoma SMMC- 7721 cells / Life Sci 78 : 1238~1245

[journal] Kasibhatla S / 2005 / A role for transferrin receptor in triggehring apoptosis when targeted with gambogic acid / Proc Natl Acad Sci USA 102 : 12095~12100

[journal] Pandey MK / 2007 / Gambogic acid, a novel ligand for transferrin receptor, potentiates TNF-induced apoptosis through modulation of the nuclear factor-kB signaling pathway / Blood 110 : 517~525

[journal] Li Z / 2006 / Effects of tongxinluo and simvastatin on the stabilization of vulnerable atherosclerotic plaques of aorta in aortic atherosclerosis and molecular mechanism there of: a comparative study with rabbits / Zhonghua Yi Xue Za Zhi 86 : 3146~3150

[journal] Hernández-Perera O / 1998 / Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin- 1 and endothelial nitric oxide synthase in vascular endothelial cells / J Clin Invest 15 : 2711~2719

[journal] 김경곤 / 2009 / An Effective Isolation of the Vascular Endothelial and Smooth Muscle Cells from the Mouse Aorta / Anatomy and Cell Biology / 대한해부학회 42(2) : 93~104

[journal] O’Sullivan M / 2003 / Differential cyclin E expression in human in stent stenosis vascular smooth muscle cells identifies targets for selective anti-restenotic therapy / Cardiovasc Res 60 : 673~683

[journal] Chen L / 2010 / 4-(methylnitro-samino)-1-(3-pyridyl)-1- butanone induces CRM1-dependent p53 nuclear accumulation in human bronchial epithelial cells / Toxicol Sci 116 : 206~215

[journal] Rahman MA / 2013 / Cytotoxic effect of gambogic acid on SH-SY5Y neuroblastoma cells is mediated by intrinsic caspase-dependent signaling pathway / Mol Cell Biochem 377(1) : 187~196

[journal] Weng C / 2005 / Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis- inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells / J Biol Chem 280 : 10491~10500

[journal] Qin W / 2012 / Simvastatin suppresses apoptosis in vulnerable atherosclerotic plaques through regulating the expression of p53, Bcl-2 and Bcl-xL / Cardiovasc Drugs Ther 26 : 23~30

KJCKorea
Journal Central

Anatomy & Biological Anthropology 2023 KCI Impact Factor : 0.33

Gambogic Acid Induced Apoptosis through Activation of Caspase-dependent Pathway in Aortic Smooth Muscle Cells

ABSTRACT

KEYWORDS

Citation status

* References for papers published after 2023 are currently being built.

Anatomy & Biological Anthropology 2023 KCI Impact Factor : 0.33

Gambogic Acid Induced Apoptosis through Activation of Caspase-dependent Pathway in Aortic Smooth Muscle Cells

ABSTRACT

KEYWORDS

Statistics

Tools

Issue List

Citation status

KCI Citation Counts (0)

REFERENCES (27) * References for papers published after 2023 are currently being built.

Search PDF

Citation

* References for papers published after 2023 are currently being built.