Objective To investigate the proliferation inhibitory effect and to explore the molecular mechanism of curcumin on pulmonary fibroblasts. Methods Fibroblasts derived from lung tissue of patients with idiopathic pulmonary fibrosis ( IPF) was cultured in vitro and incubated with curcumin at different concentrations for different time. Fibroblasts were randomized into 5 groups, ie. a control group and 4 curcumin groups ( intervened by 5, 10, 20, 40 μmol / L curcumin, respectively) . MTT assay was used to determine the inhibitory rate of curcumin on the proliferation of pulmonary fibroblasts. Apoptosis and the Caspase-3 expression of pulmonary fibroblasts were identified by flow cytometry ( FCM) . Variables were compared with One-Way ANOVA. The correlations between variables were analyzed using Pearson’scorrelation coefficient. Results Curcumin inhibited pulmonary fibroblasts proliferation in a dose-dependent and time-dependent manner( r =0. 886, r = 0. 832, respectively, all P lt; 0. 01) . Apoptosis rate of pulmonary fibroblasts in 4 curcumin groups was ( 29. 58 ±2. 13) % , ( 64. 36 ±3. 92) %, ( 72. 98 ±4. 42) % , ( 83. 14 ±2. 51) % , respectively, which was significantly higher than that in the control group[ ( 3. 84 ±1. 88) % , P lt;0. 01] . The positive expression rate of apoptosis-regulating protein caspase-3 was ( 26. 24 ±3. 64) % ,( 44. 87 ±5. 31) % , ( 57. 44 ±4. 23) % , ( 73. 65 ±5. 01) % , respectively, which was significantly higher than that of the control group[ ( 4. 02 ±0. 62) % , P lt; 0. 01] . Conclusions In vitro, curcumin can significantly inhibit proliferation and induce apoptosis of pulmonary fibroblasts of patients with IPF. The mechanism maybe associated with up-regulating expression of Caspase-3.
Citation：
GAO Wei,ZHANG Deping,CHEN Bi.. Mechanism of Pulmonary Fibroblasts Apoptosis Induced by Curcumin. Chinese Journal of Respiratory and Critical Care Medicine, 2009, 09(2): 186-189. doi:
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Tourkina E, Gooz P, Oates JC, et al. Curcumin-induced apoptosis in scleroderma lung fibroblasts: role of protein kinase cepsilon. Am J Respir Cell Mol Biol, 2004, 31: 28-35.
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Phan SH. The myofibroblast in pulmonary fibrosis. Chest, 2002 , 122( Suppl 6) : S286-S289.
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Liu HL, Chen Y, Cui GH, et al. Curcumin, a potent anti-tumor reagent, is a novel histone deacetylase inhibitor regulating B-NHL cell line Raj i proliferation. Acta Pharmacol Sin, 2005, 26 : 603-609.
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张德平, 邱慧, 庄谊. 姜黄素干预对博莱霉素诱导的大鼠肺纤维化的影响. 中华结核和呼吸杂志, 2007, 10: 197-201.
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陈碧, 张德平. 姜黄素干预对实验性肺间质纤维化的影响. 中国呼吸与危重监护杂志, 2007, 6: 208-212.
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Fan G, Ma X, Wong PY, et al. p53 dephosphorylation and p21 ( Cip1 /Waf1 ) translocation correlate with caspase-3 activation in TGF-beta1-induced apoptosis of HuH-7 cells. Apoptosis, 2004, 9:211-221.
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- 1. Punithavathi D, Venkatesan N, Babu M. Protective effects of curcumin against amiodarone-induced pulmonary fibrosis in rats. Br J Pharmacol, 2003, 139: 1342-1350.
- 2. 中华医学会呼吸病学分会. 特发性肺间质纤维化诊断和治疗指南( 草案) . 现代实用医学杂志, 2003, 15: 129-131.
- 3. Willis BC, Liebler JM, Luby-Phelps K, et al. Induction of epithelialmesenchymal transition in alveolar epithelia1 cells by transforming growth factor-beta1: potential role in idiopathic pulmonary fibrosis.Am J Pathol, 2005, 166: 1321-1332.
- 4. Wang R, Ramos C, Joshi I, et al. Human lung myofibroblast-derived inducers of alveolar epithelial apoptosis identified as angiotensin peptides. Am J Physiol, 1999, 277: L1158-L1164.
- 5. Tourkina E, Gooz P, Oates JC, et al. Curcumin-induced apoptosis in scleroderma lung fibroblasts: role of protein kinase cepsilon. Am J Respir Cell Mol Biol, 2004, 31: 28-35.
- 6. Phan SH. The myofibroblast in pulmonary fibrosis. Chest, 2002 , 122( Suppl 6) : S286-S289.
- 7. Liu HL, Chen Y, Cui GH, et al. Curcumin, a potent anti-tumor reagent, is a novel histone deacetylase inhibitor regulating B-NHL cell line Raj i proliferation. Acta Pharmacol Sin, 2005, 26 : 603-609.
- 8. 张德平, 邱慧, 庄谊. 姜黄素干预对博莱霉素诱导的大鼠肺纤维化的影响. 中华结核和呼吸杂志, 2007, 10: 197-201.
- 9. 陈碧, 张德平. 姜黄素干预对实验性肺间质纤维化的影响. 中国呼吸与危重监护杂志, 2007, 6: 208-212.
- 10. Fan G, Ma X, Wong PY, et al. p53 dephosphorylation and p21 ( Cip1 /Waf1 ) translocation correlate with caspase-3 activation in TGF-beta1-induced apoptosis of HuH-7 cells. Apoptosis, 2004, 9:211-221.
