Analysis of tanshinone IIA induced cellular apoptosis in leukemia cells by genome-wide expression profiling

详细信息    查看全文

• 作者：Chang Liu (1)
  Jianqin Li (1)
  Liangjie Wang (4)
  Fuqun Wu (2)
  Linfang Huang (1)
  Yue Xu (2) (3)
  Jieyu Ye (2)
  Bin Xiao (2) (3)
  Fanyi Meng (2)
  Shilin Chen (1)
  Mo Yang (2) (4)
  
• 关键词：Gene expression profiling ; apoptosis ; CCL2 ; U ; 937 cell lines ; tanshinone IIA (Tan IIA)
• 刊名：BMC Complementary and Alternative Medicine
• 出版年：2012
• 出版时间：December 2012
• 年：2012
• 卷：12
• 期：1
• 全文大小：853KB
• 参考文献：1. Stass SAS, Harold R, Rock , William R: / Handbook of hematologic pathology. New York: Marcel Dekker; 2000.
  2. Wargovich MJ, Woods C, Hollis DM, Zander ME: Herbals, cancer prevention and health. / J Nutr 2001,131(11 Suppl):3034S-3036S.
  3. Boon H, Wong J: Botanical medicine and cancer: a review of the safety and efficacy. / Expert Opin Pharmacother 2004,5(12):2485-501. CrossRef
  4. Sung HJ, Choi SM, Yoon Y, An KS: Tanshinone IIA, an ingredient of Salvia miltiorrhiza BUNGE, induces apoptosis in human leukemia cell lines through the activation of caspase-3. / Exp Mol Med 1999,31(4):174-78.
  5. Liu JJ, Zhang Y, Lin DJ, Xiao RZ: Tanshinone IIA inhibits leukemia THP-1 cell growth by induction of apoptosis. / Oncol Rep 2009,21(4):1075-081.
  6. Zhang K, Li J, Meng W, Xing H, Yang Y: C/EBPbeta and CHOP participate in Tanshinone IIA-induced differentiation and apoptosis of acute promyelocytic leukemia cells in vitro. / Int J Hematol 2010,92(4):571-78. CrossRef
  7. Yuan SL, Wei YQ, Wang XJ, Xiao F, Li SF, Zhang J: Growth inhibition and apoptosis induction of tanshinone II-A on human hepatocellular carcinoma cells. / World J Gastroenterol 2004,10(14):2024-028.
  8. Su CC, Lin YH: Tanshinone IIA inhibits human breast cancer cells through increased Bax to Bcl-xL ratios. / Int J Mol Med 2008,22(3):357-61.
  9. Lu Q, Zhang P, Zhang X, Chen J: Experimental study of the anti-cancer mechanism of tanshinone IIA against human breast cancer. / Int J Mol Med 2009,24(6):773-80. CrossRef
  10. Zhou L, Chan WK, Xu N, Xiao K, Luo H, Luo KQ, Chang DC: Tanshinone IIA, an isolated compound from Salvia miltiorrhiza Bunge, induces apoptosis in HeLa cells through mitotic arrest. / Life Sci 2008,83(11-2):394-03. CrossRef
  11. Pan TL, Hung YC, Wang PW, Chen ST, Hsu TK, Sintupisut N, Cheng CS, Lyu PC: Functional proteomic and structural insights into molecular targets related to the growth inhibitory effect of tanshinone IIA on HeLa cells. / Proteomics 2010,10(5):914-29.
  12. Chiu TL, Su CC: Tanshinone IIA induces apoptosis in human lung cancer A549 cells through the induction of reactive oxygen species and decreasing the mitochondrial membrane potential. / Int J Mol Med 2010,25(2):231-36.
  13. van de Loosdrecht AA, Beelen RH, Ossenkoppele GJ, Broekhoven MG, Langenhuijsen MM: A tetrazolium-based colorimetric MTT assay to quantitate human monocyte mediated cytotoxicity against leukemic cells from cell lines and patients with acute myeloid leukemia. / J Immunol Methods 1994,174(1-):311-20. CrossRef
  14. Liu C, Li J, Meng FY, Liang SX, Deng R, Li CK, Pong NH, Lau CP, Cheng SW, Ye JY, / et al.: Polysaccharides from the root of Angelica sinensis promotes hematopoiesis and thrombopoiesis through the PI3K/AKT pathway. / BMC Complement Altern Med 2010, 10:79. CrossRef
  15. Li C, Wong WH: / DNA-chip analyzer (dChip). New York: Springer; 2003.
  16. Li C, Hung Wong W: Model-based analysis of oligonucleotide arrays: model validation, design issues and standard error application. / Genome Biol 2001,2(8):RESEARCH0032.
  17. Li C, Wong WH: Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. / Proc Natl Acad Sci USA 2001,98(1):31-6. CrossRef
  18. Doniger SW, Salomonis N, Dahlquist KD, Vranizan K, Lawlor SC, Conklin BR: MAPPFinder: using Gene Ontology and GenMAPP to create a global gene-expression profile from microarray data. / Genome Biol 2003,4(1):R7. CrossRef
  19. Zhou C, Poulton EJ, Grun F, Bammler TK, Blumberg B, Thummel KE, Eaton DL: The dietary isothiocyanate sulforaphane is an antagonist of the human steroid and xenobiotic nuclear receptor. / Mol Pharmacol 2007,71(1):220-29. CrossRef
  20. Yu C, Ye S, Sun H, Liu Y, Gao L, Shen C, Chen S, Zeng S: PXR-mediated transcriptional activation of CYP3A4 by cryptotanshinone and tanshinone IIA. / Chem Biol Interact 2009,177(1):58-4. CrossRef
  21. Broxmeyer HE: Regulation of hematopoiesis by chemokine family members. / Int J Hematol 2001,74(1):9-7. CrossRef
  22. Murdoch C, Finn A: Chemokine receptors and their role in inflammation and infectious diseases. / Blood 2000,95(10):3032-043.
  23. Deshmane SL, Kremlev S, Amini S, Sawaya BE: Monocyte chemoattractant protein-1 (MCP-1): an overview. / J Interferon Cytokine Res 2009,29(6):313-26. CrossRef
  24. Lee JS, Yang EJ, Kim IS: The roles of MCP-1 and protein kinase C delta activation in human eosinophilic leukemia EoL-1 cells. / Cytokine 2009,48(3):186-95. CrossRef
  25. Soria G, Yaal-Hahoshen N, Azenshtein E, Shina S, Leider-Trejo L, Ryvo L, Cohen-Hillel E, Shtabsky A, Ehrlich M, Meshel T, / et al.: Concomitant expression of the chemokines RANTES and MCP-1 in human breast cancer: a basis for tumor-promoting interactions. / Cytokine 2008,44(1):191-00. CrossRef
  26. Soria G, Ben-Baruch A: The inflammatory chemokines CCL2 and CCL5 in breast cancer. / Cancer Lett 2008,267(2):271-85. CrossRef
  27. Roca H, Varsos ZS, Pienta KJ: CCL2 is a negative regulator of AMP-activated protein kinase to sustain mTOR complex-1 activation, survivin expression, and cell survival in human prostate cancer PC3 cells. / Neoplasia 2009,11(12):1309-317.
  28. Khorooshi R, Babcock AA, Owens T: NF-kappaB-driven STAT2 and CCL2 expression in astrocytes in response to brain injury. / J Immunol 2008,181(10):7284-291.
  29. Ueda A, Okuda K, Ohno S, Shirai A, Igarashi T, Matsunaga K, Fukushima J, Kawamoto S, Ishigatsubo Y, Okubo T: NF-kappa B and Sp1 regulate transcription of the human monocyte chemoattractant protein-1 gene. / J Immunol 1994,153(5):2052-063.
  30. Zhou C, Tabb MM, Nelson EL, Grun F, Verma S, Sadatrafiei A, Lin M, Mallick S, Forman BM, Thummel KE, / et al.: Mutual repression between steroid and xenobiotic receptor and NF-kappaB signaling pathways links xenobiotic metabolism and inflammation. / J Clin Invest 2006,116(8):2280-289. CrossRef
  31. Gu X, Ke S, Liu D, Sheng T, Thomas PE, Rabson AB, Gallo MA, Xie W, Tian Y: Role of NF-kappaB in regulation of PXR-mediated gene expression: a mechanism for the suppression of cytochrome P-450 3A4 by proinflammatory agents. / J Biol Chem 2006,281(26):17882-7889. CrossRef
  32. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6882/12/5/prepub
  
• 作者单位：Chang Liu (1)
  Jianqin Li (1)
  Liangjie Wang (4)
  Fuqun Wu (2)
  Linfang Huang (1)
  Yue Xu (2) (3)
  Jieyu Ye (2)
  Bin Xiao (2) (3)
  Fanyi Meng (2)
  Shilin Chen (1)
  Mo Yang (2) (4)
  
  1. Institute of Medicinal Plant Development, Chinese Academy of Medical Science, 151 MaLianWa North Road, Beijing, 100193, P.R.China
  4. LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, P.R. China
  2. Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, P.R. China
  3. Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, P.R.China
  

文摘

Background Tanshinone IIA (Tan IIA) is a diterpene quinone extracted from the root of Salvia miltiorrhiza, a Chinese traditional herb. Although previous studies have reported the anti-tumor effects of Tan IIA on various human cancer cells, the underlying mechanisms are not clear. The current study was undertaken to investigate the molecular mechanisms of Tan IIA's apoptotic effects on leukemia cells in vitro. Methods The cytotoxicity of Tan IIA on different types of leukemia cell lines was evaluated by the 3-[4,5-dimethylthiazol-2,5]-diphenyl tetrazolium bromide (MTT) assay on cells treated without or with Tan IIA at different concentrations for different time periods. Cellular apoptosis progression with and without Tan IIA treatment was analyzed by Annexin V and Caspase 3 assays. Gene expression profiling was used to identify the genes regulated after Tan IIA treatment and those differentially expressed among the five cell lines. Confirmation of these expression regulations was carried out using real-time quantitative PCR and ELISA. The antagonizing effect of a PXR inhibitor L-SFN on Tan IIA treatment was tested using Colony Forming Unit Assay. Results Our results revealed that Tan IIA had different cytotoxic activities on five types of leukemia cells, with the highest toxicity on U-937 cells. Tan IIA inhibited the growth of U-937 cells in a time- and dose-dependent manner. Annexin V and Caspase-3 assays showed that Tan IIA induced apoptosis in U-937 cells. Using gene expression profiling, 366 genes were found to be significantly regulated after Tan IIA treatment and differentially expressed among the five cell lines. Among these genes, CCL2 was highly expressed in untreated U-937 cells and down-regulated significantly after Tan IIA treatment in a dose-dependent manner. RT-qPCR analyses validated the expression regulation of 80% of genes. Addition of L- sulforaphane (L-SFN), an inhibitor of Pregnane × receptor (PXR) significantly attenuated Tan IIA's effects using colony forming assays. Conclusions Tan IIA has significant growth inhibition effects on U-937 cells through the induction of apoptosis. And Tan IIA-induced apoptosis might result from the activation of PXR, which suppresses the activity of NF-κB and lead to the down-regulation of CCL2 expression.