DOI QR코드

DOI QR Code

Matrine Reduces Proliferation of Human Lung Cancer Cells by Inducing Apoptosis and Changing miRNA Expression Profiles

  • Liu, Yong-Qi (Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University) ;
  • Li, Yi (Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University) ;
  • Qin, Jie (Institute of Systems Biology and TCM Transformation, Gansu Traditional Chinese Medical University) ;
  • Wang, Qian (Institute of Systems Biology and TCM Transformation, Gansu Traditional Chinese Medical University) ;
  • She, Ya-Li (Institute of Systems Biology and TCM Transformation, Gansu Traditional Chinese Medical University) ;
  • Luo, Ya-Li (Institute of Systems Biology and TCM Transformation, Gansu Traditional Chinese Medical University) ;
  • He, Jian-Xin (Institute of Systems Biology and TCM Transformation, Gansu Traditional Chinese Medical University) ;
  • Li, Jing-Ya (Institute of Systems Biology and TCM Transformation, Gansu Traditional Chinese Medical University) ;
  • Xie, Xiao-Dong (Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University)
  • Published : 2014.03.01

Abstract

Matrine, a main active component extracted from dry roots of Sophora flavecens, has been reported to exert antitumor effects on A549 human non-small lung cancer cells, but its mechanisms of action remain unclear. To determine effects of matrine on proliferation of A549 cells and assess possible mechanisms, MTT assays were employed to detect cytotoxicity, along with o flow cytometric analysis of DNA content of nuclei of cells following staining with propidium iodide to analyze cell cycle distribution. Western blotting was performed to determined expression levels of Bax, Bcl-2, VEGF and HDAC1, while a microarray was used to assessed changes of miRNA profiles. In the MTT assay, matrine suppressed growth of human lung cancer cell A549 in a dose- and timedependent manner at doses of 0.25-2.5 mg/ml for 24h, 48h or 72h. Matrine induced cell cycle arrest in G0/G1 phase and decreased the G2/M phase, while down-regulating the expression of Bcl2 protein, leading to a reduction in the Bcl-2/Bax ratio. In addition, matrine down regulated the expression level of VEGF and HDAC1 of A549 cells. Microarray analysis demonstrated that matrine altered the expression level of miRNAs compared with untreated control A549 cells. In conclusion, matrine could inhibit proliferation of A549 cells, providing useful information for understanding anticancer mechanisms.

References

  1. Ai J, Gao HH, He SZ, et al (2001). Effects of matrine, artemisinin, tetrandrine on cytosolic [Ca2+]i in guinea pig ventricular myocytes. Acta Pharmacol Sin, 22, 512-5.
  2. Antignani A, Youle RJ (2006). How do Bax and Bak lead to permeabilization of the outer mitochondrial membrane? Curr Opin Cell Biol, 18, 685-9. https://doi.org/10.1016/j.ceb.2006.10.004
  3. Blower PE, Chung JH, Verducci JS, et al (2008). MicroRNAs modulate the chemosensitivity of tumor cells. Mol Cancer Ther, 7, 1-9.
  4. Bremnes RM, Camps C, Sirera R (2006). Angiogenesis in non-small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood. Lung Cancer, 51, 143-58. https://doi.org/10.1016/j.lungcan.2005.09.005
  5. Cai X, Gao S, Cai J, Wu Y, Deng H (2009). Artesunate induced morphological and mechanical changes of Jurkat cell studied by AFM. Scanning, 31, 83-9. https://doi.org/10.1002/sca.20144
  6. Chang C, Rao DL, Qiu XM, Wang H, Xiong L (2014). [The inhibitory effect of matrine on the growth of human colorectal cancer HT29 cells: an experimental observation]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 34, 62-5.
  7. Cheng H, Xia B, Zhang L, et al (2006). Matrine improves 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis in mice. Pharmacol Res, 53, 202-8. https://doi.org/10.1016/j.phrs.2005.11.001
  8. Cordes N, Beinke C, Plasswilm L, van Beuningen D (2004). Irradiation and various cytotoxic drugs enhance tyrosine phosphorylation and beta (1)-integrin clustering in human A549 lung cancer cells in a substratum-dependent manner in vitro. Strahlenther Onkol, 180, 157-64. https://doi.org/10.1007/s00066-004-1144-2
  9. Cress WD, Seto E (2000). Histone deacetylases, transcriptional control, and cancer. J cell Physiol, 184, 1-16. https://doi.org/10.1002/(SICI)1097-4652(200007)184:1<1::AID-JCP1>3.0.CO;2-7
  10. Croce CM, Calin GA (2005). miRNAs, cancer, and stem cell division. Cell, 122, 6-7. https://doi.org/10.1016/j.cell.2005.06.036
  11. Eder M, Scherr M (2005). MicroRNA and lung cancer. N Engl J Med, 352, 2446-8. https://doi.org/10.1056/NEJMcibr051201
  12. Erridge SC, Moller H, Price A, Brewster D (2007). International comparisons of survival from lung cancer: pitfalls and warnings. Nat Clin Pract Oncol, 4, 570-7. https://doi.org/10.1038/ncponc0932
  13. Esquela-Kerscher A, Slack FJ (2006). Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer, 6, 259-69. https://doi.org/10.1038/nrc1840
  14. Fritzsche FR, Weichert W, Roske A, et al (2008). Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer. BMC Cancer, 8, 381. https://doi.org/10.1186/1471-2407-8-381
  15. Green DR, Kroemer G (2004). The pathophysiology of mitochondrial cell death. Science, 305, 626-9. https://doi.org/10.1126/science.1099320
  16. Gregory RI, Shiekhattar R (2005). MicroRNA biogenesis and cancer. Cancer Res, 65, 3509-12. https://doi.org/10.1158/0008-5472.CAN-05-0298
  17. Hengartner MO (2000). The biochemistry of apoptosis. Nature, 407, 770-6. https://doi.org/10.1038/35037710
  18. Hernandez-Hernandez OT, Camacho-Arroyo I (2013). Regulation of gene expression by progesterone in cancer cells: effects on cyclin D1, EGFR and VEGF. Mini Rev Med Chem, 13, 635-42. https://doi.org/10.2174/1389557511313050002
  19. Hu MJ, Zeng H, Wu YL, et al (2005). Synergistic effects of matrine and 5-fluorouracil on tumor growth of the implanted gastric cancer in nude mice.Chin J Dig Dis, 6, 68-71. https://doi.org/10.1111/j.1443-9573.2005.00201.x
  20. Hu ZL, Zhang JP, Qian DH, et al (1996). Effects of matrine on mouse splenocyte proliferation and release of interleukin-1 and -6 from peritoneal macrophages in vitro. Zhongguo Yao Li Xue Bao, 17, 259-61.
  21. Jiang C, Yang YF, Cheng SH (2004). Fas ligand gene therapy for vascular intimal hyperplasia. Curr Gene Ther, 4, 33-9. https://doi.org/10.2174/1566523044578022
  22. Jiang H, Hou C, Zhang S, et al (2007). Matrine upregulates the cell cycle protein E2F-1 and triggers apoptosis via the mitochondrial pathway in K562 cells. Eur J Pharmacol, 559, 98-108. https://doi.org/10.1016/j.ejphar.2006.12.017
  23. Jiang QQ, Liu B, Yuan T (2013). MicroRNA-16 inhibits bladder cancer proliferation by targeting cyclin D1. Asian Pac J Cancer Prev, 14, 4127-30. https://doi.org/10.7314/APJCP.2013.14.7.4127
  24. Johnson SM, Grosshans H, Shingara J, et al (2005). RAS is regulated by the let-7 microRNA family. Cell, 120, 635-47. https://doi.org/10.1016/j.cell.2005.01.014
  25. Kallsen K, Andresen E, Heine H (2012). Histone deacetylase (HDAC) 1 controls the expression of beta defensin 1 in human lung epithelial cells. PloS One, 7, e50000. https://doi.org/10.1371/journal.pone.0050000
  26. Krusche CA, Wulfing P, Kersting C, et al (2005). Histone deacetylase-1 and -3 protein expression in human breast cancer: a tissue microarray analysis. Breast Cancer Res Treat, 90, 15-23. https://doi.org/10.1007/s10549-004-1668-2
  27. Langer R, Mutze K, Becker K, et al (2010). Expression of class I histone deacetylases (HDAC1 and HDAC2) in oesophageal adenocarcinomas: an immunohistochemical study. J Clin Pathol, 63, 994-8. https://doi.org/10.1136/jcp.2010.080952
  28. Lee EM, Shin S, Cha HJ, et al (2009). Suberoylanilide hydroxamic acid (SAHA) changes microRNA expression profiles in A549 human non-small cell lung cancer cells. Int J Mol Med, 24, 45-50.
  29. Li N, Tie XJ, Liu PJ, et al (2013a). Effects of down-regulation of HDAC6 expression on proliferation, cell cycling and migration of esophageal squamous cell carcinoma cells and related molecular mechanisms. Asian Pac J Cancer Prev, 14, 685-9. https://doi.org/10.7314/APJCP.2013.14.2.685
  30. Li Y, Zhang S, Geng JX, Hu XY (2013b). Curcumin inhibits human non-small cell lung cancer A549 cell proliferation through regulation of Bcl-2/Bax and cytochrome C. Asian Pac J Cancer Prev, 14, 4599-2. https://doi.org/10.7314/APJCP.2013.14.8.4599
  31. Liang J, Qian Y, Xu D, Yin Q, Pan HJ (2013). Serum tumor markers, hypoxia-inducible factor-1alpha HIF-1alpha and vascular endothelial growth factor, in patients with nonsmall cell lung cancer before and after intervention. Asian Pac J Cancer Prev, 14, 3851-4. https://doi.org/10.7314/APJCP.2013.14.6.3851
  32. Liu J, Zhu M, Shi R, Yang M (2003). Radix Sophorae flavescentis for chronic hepatitis B: a systematic review of randomized trials. Am J Chin Med, 31, 337-54. https://doi.org/10.1142/S0192415X03001107
  33. Liu XS, Jiang J, Jiao XY, Wu YE, Lin JH (2006). Matrineinduced apoptosis in leukemia U937 cells: involvement of caspases activation and MAPK-independent pathways. Planta Med, 72, 501-6. https://doi.org/10.1055/s-2006-931534
  34. Liu XY, Fang H, Yang ZG, et al (2008). Matrine inhibits invasiveness and metastasis of human malignant melanoma cell line A375 in vitro. Int J Dermatol, 47, 448-56. https://doi.org/10.1111/j.1365-4632.2008.03627.x
  35. Liu ZY, Zhang GL, Wang MM, Xiong YN, Cui HQ (2011). MicroRNA-663 targets TGFB1 and regulates lung cancer proliferation. Asian Pac J Cancer Prev, 12, 2819-23.
  36. Long Y, Lin XT, Zeng KL, Zhang L (2004). Efficacy of intramuscular matrine in the treatment of chronic hepatitis B. Hepatobiliary Pancreat Dis Int, 3, 69-72.
  37. Luo C, Zhu Y, Jiang T, et al (2007). Matrine induced gastric cancer MKN45 cells apoptosis via increasing pro-apoptotic molecules of Bcl-2 family. Toxicology, 229, 245-52. https://doi.org/10.1016/j.tox.2006.10.020
  38. Minamiya Y, Ono T, Saito H, et al (2011). Expression of histone deacetylase 1 correlates with a poor prognosis in patients with adenocarcinoma of the lung. Lung Cancer, 74, 300-4. https://doi.org/10.1016/j.lungcan.2011.02.019
  39. Nakagawa M, Oda Y, Eguchi T, et al (2007). Expression profile of class I histone deacetylases in human cancer tissues. Oncol Rep, 18, 769-74.
  40. Nana-Sinkam SP, Geraci MW (2006). MicroRNA in lung cancer. J Thorac Oncol, 1, 929-31. https://doi.org/10.1097/01243894-200611000-00002
  41. Sasaki H, Moriyama S, Nakashima Y, et al (2004). Histone deacetylase 1 mRNA expression in lung cancer. Lung Cancer, 46, 171-8. https://doi.org/10.1016/j.lungcan.2004.03.021
  42. Shivapurkar N, Reddy J, Chaudhary PM, Gazdar AF (2003). Apoptosis and lung cancer: a review. J Cell Biochem, 88, 885-98. https://doi.org/10.1002/jcb.10440
  43. Takamizawa J, Konishi H, Yanagisawa K, et al (2004). Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res, 64, 3753-6. https://doi.org/10.1158/0008-5472.CAN-04-0637
  44. Tan C, Qian X, Jia R, Wu M, Liang Z (2013). Matrine induction of reactive oxygen species activates p38 leading to caspasedependent cell apoptosis in non-small cell lung cancer cells. Oncol Rep, 30, 2529-35.
  45. Thiagalingam S, Cheng KH, Lee HJ, et al (2003). Histone deacetylases: unique players in shaping the epigenetic histone code. Ann N Y Acad Sci, 983, 84-100. https://doi.org/10.1111/j.1749-6632.2003.tb05964.x
  46. Thorburn A (2004). Death receptor-induced cell killing. Cell Signal, 16, 139-44. https://doi.org/10.1016/j.cellsig.2003.08.007
  47. Tsang WP, Kwok TT (2009). The miR-18a* microRNA functions as a potential tumor suppressor by targeting on K-Ras. Carcinogenesis, 30, 953-9. https://doi.org/10.1093/carcin/bgp094
  48. Ulasli SS, Celik S, Gunay E, et al (2013). Anticancer effects of thymoquinone, caffeic acid phenethyl ester and resveratrol on A549 non-small cell lung cancer cells exposed to benzo (a)pyrene. Asian Pac J Cancer Prev, 14, 6159-64. https://doi.org/10.7314/APJCP.2013.14.10.6159
  49. Wang JS, Ji AF, Wan HJ, et al (2012). Gene silencing of betacatenin by RNAi inhibits proliferation of human esophageal cancer cells by inducing G0/G1 cell cycle arrest. Asian Pac J Cancer Prev, 13, 2527-32. https://doi.org/10.7314/APJCP.2012.13.6.2527
  50. Weichert W, Roske A, Gekeler V, et al (2008a). Association of patterns of class I histone deacetylase expression with patient prognosis in gastric cancer: a retrospective analysis. Lancet Oncol, 9, 139-48. https://doi.org/10.1016/S1470-2045(08)70004-4
  51. Weichert W, Roske A, Niesporek S, et al (2008b). Class I histone deacetylase expression has independent prognostic impact in human colorectal cancer: specific role of class I histone deacetylases in vitro and in vivo. Clin Cancer Res, 14, 1669-77. https://doi.org/10.1158/1078-0432.CCR-07-0990
  52. Xu CQ, Dong DL, Du ZM, et al (2004). Comparison of the anti-arrhythmic effects of matrine and berbamine with amiodarone and RP58866. Yao Xue Xue Bao, 39, 691-4 (in Chinese).
  53. Yang Y, Liu L, Zhang Y, et al (2014). MiR-503 targets PI3K p85 and IKK-beta and suppresses progression of non-small cell lung cancer. Int J Cancer, Epub ahead of print.
  54. Yao Q, Sun JG, Ma H, et al (2014). Monitoring microRNAs Using a Molecular Beacon in CD133+/ CD338+ Human Lung Adenocarcinoma-initiating A549 Cells. Asian Pac J Cancer Prev, 15, 161-6. https://doi.org/10.7314/APJCP.2014.15.1.161
  55. Zhang BH, Wang NS, Li XJ, Kong XJ, Cai YL (1990). Antiarrhythmic effects of matrine. Zhongguo Yao Li Xue Bao, 11, 253-7 (in Chinese).
  56. Zhang JP, Zhang M, Jin C, et al (2001a). Matrine inhibits production and actions of fibrogenic cytokines released by mouse peritoneal macrophages. Acta Pharmacol Sin, 22, 765-8.
  57. Zhang JP, Zhang M, Zhou JP, et al (2001b). Antifibrotic effects of matrine on in vitro and in vivo models of liver fibrosis in rats. Acta Pharmacol Sin, 22, 183-6.
  58. Zhang L, Wang T, Wen X, et al (2007). Effect of matrine on HeLa cell adhesion and migration. Eur J Pharmacol, 563, 69-76. https://doi.org/10.1016/j.ejphar.2007.01.073
  59. Zhang LP, Jiang JK, Tam JW, et al (2001c). Effects of matrine on proliferation and differentiation in K-562 cells. Leukemia Res, 25, 793-800. https://doi.org/10.1016/S0145-2126(00)00145-4
  60. Zhang P, Wang Z, Chong T, Ji Z (2012a). Matrine inhibits proliferation and induces apoptosis of the androgenindependent prostate cancer cell line PC-3. Mol Med Re, 5, 783-7.
  61. Zhang QC, Jiang SJ, Zhang S, Ma XB (2012b). Histone deacetylase inhibitor trichostatin A enhances anti-tumor effects of docetaxel or erlotinib in A549 cell line. Asian Pac J Cancer Prev, 13, 3471-6. https://doi.org/10.7314/APJCP.2012.13.7.3471
  62. Zhang S, Cheng B, Li H, et al (2014). Matrine inhibits proliferation and induces apoptosis of human colon cancer LoVo cells by inactivating Akt pathway. Mol Biol Rep, Epub ahead of print.
  63. Zhang S, Qi J, Sun L, et al (2009). Matrine induces programmed cell death and regulates expression of relevant genes based on PCR array analysis in C6 glioma cells. Molec Biol Reports, 36, 791-9. https://doi.org/10.1007/s11033-008-9247-y
  64. Zhu W, He J, Chen D, et al (2014). Expression of miR-29c, miR-93, and miR-429 as Potential Biomarkers for Detection of Early Stage Non-Small Lung Cancer. PloS One, 9, e87780. https://doi.org/10.1371/journal.pone.0087780

Cited by

  1. Effects of Hypobaric Conditions on Apoptosis Signalling Pathways in HeLa Cells vol.15, pp.12, 2014, https://doi.org/10.7314/APJCP.2014.15.12.5043
  2. Synergistic Effect of Ethaselen and Selenite Treatment against A549 Human Non-small Cell Lung Cancer Cells vol.15, pp.17, 2014, https://doi.org/10.7314/APJCP.2014.15.17.7129
  3. Exosome-derived microRNA-29c Induces Apoptosis of BIU-87 Cells by Down Regulating BCL-2 and MCL-1 vol.15, pp.8, 2014, https://doi.org/10.7314/APJCP.2014.15.8.3471
  4. Matrine alters microRNA expression profiles in SGC-7901 human gastric cancer cells vol.32, pp.5, 2014, https://doi.org/10.3892/or_xxxxxxxx
  5. Anti-proliferative and Apoptotic Effects of Dendrosomal Farnesiferol C on Gastric Cancer Cells vol.16, pp.13, 2015, https://doi.org/10.7314/APJCP.2015.16.13.5325
  6. Dispersive Liquid–Liquid Microextraction Combined with High-Performance Liquid Chromatography for the Simultaneous Analysis of Matrine Alkaloids in Traditional Chinese Medicine vol.54, pp.9, 2016, https://doi.org/10.1093/chromsci/bmw114
  7. Matrine reduces the proliferation of A549 cells via the p53/p21/PCNA/eIF4E signaling pathway vol.15, pp.5, 2017, https://doi.org/10.3892/mmr.2017.6331
  8. Mir-30d suppresses cell proliferation of colon cancer cells by inhibiting cell autophagy and promoting cell apoptosis vol.39, pp.6, 2017, https://doi.org/10.1177/1010428317703984
  9. Effect of matrine combined with cisplatin on the expression of XIAP in human rhabdomyosarcoma RD cells vol.12, pp.5, 2016, https://doi.org/10.3892/ol.2016.5150
  10. Oxymatrine inhibits proliferation of human bladder cancer T24 cells by inducing apoptosis and cell cycle arrest vol.13, pp.6, 2017, https://doi.org/10.3892/ol.2017.6013
  11. Matrine inhibits the progression of prostate cancer by promoting expression of GADD45B vol.78, pp.5, 2018, https://doi.org/10.1002/pros.23469