Abstract
The purpose of this study is to investigate in vitro and ex vivo effects of matrine on the growth of human lung cancer and hepatoma cells and the cancer cell migration as well as the expressions of related proteins in the cancer cells. Matrine significantly inhibited the in vitro and ex vivo growth of human non-small cell lung cancer A549 and hepatoma SMMC-7721 cells. Matrine induced the apoptosis in A549 and SMMC-7721 cells. Western blot analysis indicated that matrine dose-dependently down-regulated the expression of anti-apoptotic protein Bcl-2 and up-regulated the level of pro-apoptotic protein bax, eventually leading the reduction of ratios of Bcl-2/Bax proteins in A549 and SMMC-7721 cells. Furthermore, matrine significantly suppressed the A549 cell migration without reducing the cell viability. In addition, matrine dramatically reduced the secretion of vascular endothelial growth factor A in A549 cells. More importantly, matrine markedly enhanced the anticancer activity of anticancer agent trichostatin A (the histone deacetylase inhibitor) by strongly reducing the viability and/or the ratio of Bcl-2/Bax protein in A549 cells. Our findings suggest that matrine may have the broad therapeutic and/or adjuvant therapeutic application in the treatment of human non-small cell lung cancer and hepatoma.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- MA:
-
Matrine
- TSA:
-
Trichostatin A
- S:
-
Celecoxib
- NF-κB:
-
Nuclear factor κB
- VEGF-A:
-
Vascular endothelial growth factor A
- NSCLC:
-
Non-small cell lung cancer
References
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 51:143–158
Chen Q, Gong B, Mahmoud-Ahmed AS, Zhou A, Hsi ED, Hussein M, Almasan A (2001) Apo2L/TRAIL and Bcl-2-related proteins regulate type I interferon-induced apoptosis in multiple myeloma. Blood 98:2183–2192
Chen CH, Lai JM, Chou TY, Chen CY, Su LJ, Lee YC, Cheng TS, Hong YR, Chou CK, Whang-Peng J, Wu YC, Huang CY (2009) VEGFA upregulates FLJ10540 and modulates migration and invasion of lung cancer via PI3 K/AKT pathway. PLoS ONE 4:e5052
Gao G, Law FC (2009) Physiologically based pharmacokinetics of matrine in the rat after oral administration of pure chemical and ACAPHA. Drug Metab Dispos 37:884–891
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ (2008) Cancer statistics, 2008. CA Cancer J Clin 58:71–96
Lao Y (2005) Clinical study of matrine injection on preventing liver function damage of anti-tumor drugs during chemotherapy of breast cancer. Zhong Yao Cai 28:735–737
Liu XY, Fang H, Yang ZG, Wang XY, Ruan LM, Fang DR, Ding YG, Wang YN, Zhang Y, Jiang XL, Chen HC (2008) Matrine inhibits invasiveness and metastasis of human malignant melanoma cell line A375 in vitro. Int J Dermatol 47:448–456
Liu B, Peng XC, Zheng XL, Wang J, Qin YW (2009) MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo. Lung Cancer. doi:10.1016/j.lungcan.2009.01.010
Luo C, Zhu Y, Jiang T, Lu X, Zhang W, Jing Q, Li J, Pang L, Chen K, Qiu F, Yu X, Yang J, Huang J (2007) Matrine induced gastric cancer MKN45 cells apoptosis via increasing pro-apoptotic molecules of Bcl-2 family. Toxicology 229:245–252
Ma L, Wen S, Zhan Y, He Y, Liu X, Jiang J (2008) Anticancer effects of the Chinese medicine matrine on murine hepatocellular carcinoma cells. Planta Med 74:245–251
Oltvai ZN, Milliman C, Korsmeyer SJ (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74:609–619
Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108
Wu XL, Hang TJ, Shen JP, Zhang YD (2006) Determination and pharmacokinetic study of oxymatrine and its metabolite matrine in human plasma by liquid chromatography tandem mass spectrometry. J Pharm Biomed Anal 41:918–924
Zhang G, Miura Y, Yagasaki K (1999) Effects of green, oolong and black teas and related components on the proliferation and invasion of hepatoma cells in culture. Cytotechnology 31:37–44
Zhang G, Miura Y, Yagasaki K (2000) Induction of apoptosis and cell cycle arrest in cancer cells by in vivo metabolites of teas. Nutr Cancer 38:265–273
Zhang G, Miura Y, Yagasaki K (2001) Inhibitory effects of theanine and sera from theanine-fed rats on receptor-mediated cancer cell beneath mesothelial-cell monolayers. Cytotechnology 36:195–200
Zhang L, Wang T, Wen X, Wei Y, Peng X, Li H, Wei L (2007) Effect of matrine on HeLa cell adhesion and migration. Eur J Pharmacol 563:69–76
Zhang L, Liu W, Zhang R, Wang Z, Shen Z, Chen X, Bi K (2008) Pharmacokinetic study of matrine, oxymatrine and oxysophocarpine in rat plasma after oral administration of Sophora flavescens Ait. extract by liquid chromatography tandem mass spectrometry. J Pharm Biomed Anal 47:892–898
Acknowledgments
This work is supported in part by grants from the Ministry of Education of the People’s Republic of China to G. Z, from the Ministry of Human Resources and Social Security of the People’s Republic of China to G. Z, Priority Project Fund of Yantai University to G. Z, and Projects from the Department of Science and Technology of Shandong Province to G. Z. (Y2008C71; 2009GG10002087).
Author information
Authors and Affiliations
Corresponding author
Additional information
Ying Zhang (No. of student: 0725100168), Hui Zhang (No. of student: 200823130108), and Pengfei Yu contributed equally to this work.
Rights and permissions
About this article
Cite this article
Zhang, Y., Zhang, H., Yu, P. et al. Effects of matrine against the growth of human lung cancer and hepatoma cells as well as lung cancer cell migration. Cytotechnology 59, 191–200 (2009). https://doi.org/10.1007/s10616-009-9211-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10616-009-9211-2