Skip to main content
Top
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 6/2012

01-06-2012 | Pathology

Effects of matrine on proliferation and apoptosis of cultured retinoblastoma cells

Authors: Bowen Zhao, Bin Li, Shuwei Bai, Ling Shen, Ruojin Ren, Jost B. Jonas, Xiaolin Xu, Qingjun Lu, Qian Liu

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 6/2012

Login to get access

Abstract

Background

Extracted from the traditional Chinese medicine of Kushen, matrine is an alkaloid with potential anti-neoplastic and anti-inflammatory effects. Here, we examined the effect of matrine on proliferation and apoptosis of cultured retinoblastoma cells.

Methods

The retinoblastoma cell lines Y79, WERI-RB1 and SO-RB50 were treated with matrine in increasing concentrations from 0.2-1.1 mg/ml for 24 hours, and the cell proliferation rate was measured. The cells were exposed to matrine at 50% inhibition concentration (IC50) for 12, 24 and 48 hours. Cell cycle was analyzed by flow cytometry, concentration of proteins regulating cell cycle and apoptosis was determined by Western blot, apoptosis rate was measured by TUNEL staining, and cell morphology was assessed by electron transmission microscopy.

Results

The retinoblastoma cell lines Y79, WERI-RB1 and SO-RB50 showed an increased inhibition of cell proliferation with increasing matrine concentrations. Applying the IC50 concentration of matrine, the alteration of the cell cycle, including a reduced percentage of the S phase, was significantly (P < 0.01) associated with a longer treatment time by matrine. Correspondingly, the cell-cycle-associated proteins P21 and P27 were up-regulated and the protein cyclinD1 was down-regulated. The apoptosis-associated protein Bcl-2 was down-regulated, and Bax was up-regulated. In a similar manner, the apoptosis rate was significantly increased with longer treatment time.

Conclusions

Matrine added to cultures of immortalized retinoblastoma cells led to a reduced tumor cell proliferation, decreased rate of mitosis and an increased tumor cell apoptosis, paralleled by corresponding changes in the proteins regulating the cell cycle or apoptosis.
Literature
1.
go back to reference Kyogoku K, Hatayama K, Komatsu M (1973) Constituents of Chinese crude drug "Kushen" (the root of Sophora flavescens Ait.). Isolation of five new flavonoids and formononetin. Chem Pharm Bull 21:2733–2738PubMedCrossRef Kyogoku K, Hatayama K, Komatsu M (1973) Constituents of Chinese crude drug "Kushen" (the root of Sophora flavescens Ait.). Isolation of five new flavonoids and formononetin. Chem Pharm Bull 21:2733–2738PubMedCrossRef
2.
go back to reference Han J, Sun MY, Cui YM (2007) Kushen flavonoids induce apoptosis in tumor cells by inhibition of NF-kappaB activation and multiple receptor tyrosine kinase activities. Phytother Res 21:262–268PubMedCrossRef Han J, Sun MY, Cui YM (2007) Kushen flavonoids induce apoptosis in tumor cells by inhibition of NF-kappaB activation and multiple receptor tyrosine kinase activities. Phytother Res 21:262–268PubMedCrossRef
3.
go back to reference Sun MY, Zuo J, Duan JF, Han J, Fan SM, Zhang W, Zhu LF, Yao MH (2008) Antitumor activities of kushen flavonoids in vivo and in vitro. Zhong Xi Yi Jie He Xue Bao 6:51–59PubMedCrossRef Sun MY, Zuo J, Duan JF, Han J, Fan SM, Zhang W, Zhu LF, Yao MH (2008) Antitumor activities of kushen flavonoids in vivo and in vitro. Zhong Xi Yi Jie He Xue Bao 6:51–59PubMedCrossRef
4.
go back to reference Zhang Y, Zhang P, Cheng Y (2008) Structural characterization of isoprenylated flavonoids from Kushen by electrospray ionization multistage tandem mass spectrometry. J Mass Spectrom 43:1421–1431PubMedCrossRef Zhang Y, Zhang P, Cheng Y (2008) Structural characterization of isoprenylated flavonoids from Kushen by electrospray ionization multistage tandem mass spectrometry. J Mass Spectrom 43:1421–1431PubMedCrossRef
5.
go back to reference Zhang LP, Jiang JK, Tam JW, Zhang Y, Liu XS, Xu XR, Liu BZ, He YJ (2001) Effect of matrine on proliferation and differentiation in K-562 cells. Leuk Res 25:793–800PubMedCrossRef Zhang LP, Jiang JK, Tam JW, Zhang Y, Liu XS, Xu XR, Liu BZ, He YJ (2001) Effect of matrine on proliferation and differentiation in K-562 cells. Leuk Res 25:793–800PubMedCrossRef
6.
go back to reference Wan XY, Luo M, Li XD, He P (2009) Hepatoprotective and anti-hepatocarcinogenic effects of glycyrrhizin and matrine. Chem Biol Interact 181:15–19PubMedCrossRef Wan XY, Luo M, Li XD, He P (2009) Hepatoprotective and anti-hepatocarcinogenic effects of glycyrrhizin and matrine. Chem Biol Interact 181:15–19PubMedCrossRef
7.
go back to reference Liu XS, Jiang J (2006) Molecular mechanism of matrine-induced apoptosis in leukemia K562 cells. Am J Chin Med 34:1095–1103PubMedCrossRef Liu XS, Jiang J (2006) Molecular mechanism of matrine-induced apoptosis in leukemia K562 cells. Am J Chin Med 34:1095–1103PubMedCrossRef
8.
go back to reference Wu CX, Chen YH, Zheng ZX (2006) Observation on efficacy of matrine with dansheng on liver fibrosis. J Pract Med (Shi Yong Yi Xue Za Zhi) 22:1567–1568 Wu CX, Chen YH, Zheng ZX (2006) Observation on efficacy of matrine with dansheng on liver fibrosis. J Pract Med (Shi Yong Yi Xue Za Zhi) 22:1567–1568
9.
go back to reference Yu W, Li B, Ren RJ, Gao F, Li LQ, Liu XC, Wang Y (2006) The effects of matrine on cell proliferation and telomerase activity in retinoblastoma cells in vitro. Zhonghua Yan Ke Za Zhi [Chinese Journal of Ophthalmology] 42:594–599 Yu W, Li B, Ren RJ, Gao F, Li LQ, Liu XC, Wang Y (2006) The effects of matrine on cell proliferation and telomerase activity in retinoblastoma cells in vitro. Zhonghua Yan Ke Za Zhi [Chinese Journal of Ophthalmology] 42:594–599
10.
go back to reference 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 229:245–252PubMedCrossRef 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 229:245–252PubMedCrossRef
11.
go back to reference Liu JY, Hu JH, Zhu QG, Li FQ, Wang J, Sun HJ (2007) Effect of matrine on the expression of substance P receptor and inflammatory cytokines production in human skin keratinocytes and fibroblasts. Int Immunopharmacol 7:816–823PubMedCrossRef Liu JY, Hu JH, Zhu QG, Li FQ, Wang J, Sun HJ (2007) Effect of matrine on the expression of substance P receptor and inflammatory cytokines production in human skin keratinocytes and fibroblasts. Int Immunopharmacol 7:816–823PubMedCrossRef
12.
go back to reference Zhang Y, Wang S, Li Y, Xiao Z, Hu Z, Zhang J (2008) Sophocarpine and matrine inhibit the production of TNF-alpha and IL-6 in murine macrophages and prevent cachexia-related symptoms induced by colon26 adenocarcinoma in mice. Int Immunopharmacol 8:1767–1772PubMedCrossRef Zhang Y, Wang S, Li Y, Xiao Z, Hu Z, Zhang J (2008) Sophocarpine and matrine inhibit the production of TNF-alpha and IL-6 in murine macrophages and prevent cachexia-related symptoms induced by colon26 adenocarcinoma in mice. Int Immunopharmacol 8:1767–1772PubMedCrossRef
13.
go back to reference 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 47:448–456PubMedCrossRef 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 47:448–456PubMedCrossRef
14.
go back to reference Jung E, Lee J, Huh S, Lee J, Hwang H, Kim Y, Kim YW, Byun SY, Park D (2008) Matrine inhibits PMA-induced MMP-1 expression in human dermal fibroblasts. Biofactors 33:121–128PubMedCrossRef Jung E, Lee J, Huh S, Lee J, Hwang H, Kim Y, Kim YW, Byun SY, Park D (2008) Matrine inhibits PMA-induced MMP-1 expression in human dermal fibroblasts. Biofactors 33:121–128PubMedCrossRef
15.
go back to reference Xu X, Ling Q, Gao F, He ZL, Xie HY, Zheng SS (2009) Hepatoprotective effects of marine and kuhuang in liver transplant recipients. Am J Chin Med 37:27–34PubMedCrossRef Xu X, Ling Q, Gao F, He ZL, Xie HY, Zheng SS (2009) Hepatoprotective effects of marine and kuhuang in liver transplant recipients. Am J Chin Med 37:27–34PubMedCrossRef
16.
go back to reference Zhang S, Qi J, Sun L, Cheng B, Pan S, Zhou M, Sun X (2009) Matrine induces programmed cell death and regulates expression of relevant genes based on PCR array analysis in C6 glioma cells. Mol Biol Rep 36:791–799PubMedCrossRef Zhang S, Qi J, Sun L, Cheng B, Pan S, Zhou M, Sun X (2009) Matrine induces programmed cell death and regulates expression of relevant genes based on PCR array analysis in C6 glioma cells. Mol Biol Rep 36:791–799PubMedCrossRef
17.
go back to reference Zhang Y, Zhang H, Yu P, Liu Q, Liu K, Duan H, Luan G, Yagasaki K, Zhang G (2009) Effects of matrine against the growth of human lung cancer and hepatoma cells as well as lung cancer cell migration. Cytotechnology 59:191–200PubMedCrossRef Zhang Y, Zhang H, Yu P, Liu Q, Liu K, Duan H, Luan G, Yagasaki K, Zhang G (2009) Effects of matrine against the growth of human lung cancer and hepatoma cells as well as lung cancer cell migration. Cytotechnology 59:191–200PubMedCrossRef
18.
go back to reference Qin XG, Hua Z, Shuang W, Wang YH, Cui YD (2010) Effects of matrine on HepG2 cell proliferation and expression of tumor relevant proteins in vitro. Pharm Biol 48:275–281PubMedCrossRef Qin XG, Hua Z, Shuang W, Wang YH, Cui YD (2010) Effects of matrine on HepG2 cell proliferation and expression of tumor relevant proteins in vitro. Pharm Biol 48:275–281PubMedCrossRef
19.
go back to reference Zheng MQ, Pan WN, Zhu YQ (2003) Pharmacodynamic studies on matrine eye drops for experimental ocular inflammation in rabbits. Zhong Yao Xin Yao Yu Lin Chuang Yao Li [Traditional Chinese Drug Research & Clinical Pharmacology] 14:109–111 Zheng MQ, Pan WN, Zhu YQ (2003) Pharmacodynamic studies on matrine eye drops for experimental ocular inflammation in rabbits. Zhong Yao Xin Yao Yu Lin Chuang Yao Li [Traditional Chinese Drug Research & Clinical Pharmacology] 14:109–111
20.
go back to reference Luo K, Wan XG, Deng JY, Liu F (2010) Clinical observation on the therapeutic efficacy of matrine with autologous stem cell transplantation in treatment of pterygium. Shi Yong Lin Chuang Yi Xue [Practical Chinese Medicine] 11:77–78 Luo K, Wan XG, Deng JY, Liu F (2010) Clinical observation on the therapeutic efficacy of matrine with autologous stem cell transplantation in treatment of pterygium. Shi Yong Lin Chuang Yi Xue [Practical Chinese Medicine] 11:77–78
21.
go back to reference Liu DY, Ma JX, An JB, Wang M (2009) Preventive effect of matrine polyactic acid microsphere on proliferative vitreoretinopathy. Chin Ophthal Res (Yan Ke Yan Jiu) 27:950–954 Liu DY, Ma JX, An JB, Wang M (2009) Preventive effect of matrine polyactic acid microsphere on proliferative vitreoretinopathy. Chin Ophthal Res (Yan Ke Yan Jiu) 27:950–954
22.
go back to reference Liu DY, Ma JX, Cao DY, Wang JX, Liu JZ, Lv LC (2010) Sustained release ability and safety of matrine polyactic acid microsphere intravitreal injection. Chin Ophthal Res (Yan Ke Yan Jiu) 28:34–38 Liu DY, Ma JX, Cao DY, Wang JX, Liu JZ, Lv LC (2010) Sustained release ability and safety of matrine polyactic acid microsphere intravitreal injection. Chin Ophthal Res (Yan Ke Yan Jiu) 28:34–38
23.
go back to reference Shields CL, Shields JA (2006) Basic understanding of current classification and management of retinoblastoma. Curr Opin Ophthalmol 17:228–234PubMedCrossRef Shields CL, Shields JA (2006) Basic understanding of current classification and management of retinoblastoma. Curr Opin Ophthalmol 17:228–234PubMedCrossRef
24.
go back to reference Wang Y, Lin CH, Xiao RP (2010) Effect of closed thoracic drainage with central venous catheters and combining cis-platinum(DDP)with matrine to pure into the thoracic cavity with malignant pleural effusion. Hai Nan Yi Xue [Hainan Medical Journal] 21:13–15 Wang Y, Lin CH, Xiao RP (2010) Effect of closed thoracic drainage with central venous catheters and combining cis-platinum(DDP)with matrine to pure into the thoracic cavity with malignant pleural effusion. Hai Nan Yi Xue [Hainan Medical Journal] 21:13–15
25.
go back to reference Cui DG, Li SY, Wang SY (2007) Clinical evaluation if interferon α1b associated with matrine in the treatment of liver fibrosis in hepatitis B. Zhong Guo Xin Yao Za Zhi [Chinese Journal of New Drugs] 16:314–316 Cui DG, Li SY, Wang SY (2007) Clinical evaluation if interferon α1b associated with matrine in the treatment of liver fibrosis in hepatitis B. Zhong Guo Xin Yao Za Zhi [Chinese Journal of New Drugs] 16:314–316
26.
go back to reference Wan NY, Su ZW (2009) United adefovtr dipivoxil and matrine treatment efficacy analysis of hepatitis B. Si Chuan Yi Xue [Si Chuan Medical Journal] 30:930–932 Wan NY, Su ZW (2009) United adefovtr dipivoxil and matrine treatment efficacy analysis of hepatitis B. Si Chuan Yi Xue [Si Chuan Medical Journal] 30:930–932
27.
go back to reference Xie DY, Yuan ZD, Lin GJ, Peng SL (2008) Observation of curative effect of matrine injection on infant cytomegalovirus hepatitis. Shi Yong Er Ke Lin Chuang Za Zhi [Journal of Applied Clinical Pediatrics] 23:524–526 Xie DY, Yuan ZD, Lin GJ, Peng SL (2008) Observation of curative effect of matrine injection on infant cytomegalovirus hepatitis. Shi Yong Er Ke Lin Chuang Za Zhi [Journal of Applied Clinical Pediatrics] 23:524–526
28.
go back to reference Reid TW, Albert DM, Rabson AS, Russell P, Craft J, Chu EW, Tralka TS, Wilcox JL (1974) Characteristics of an established cell line of retinoblastoma. Cancer Inst 53:347–360 Reid TW, Albert DM, Rabson AS, Russell P, Craft J, Chu EW, Tralka TS, Wilcox JL (1974) Characteristics of an established cell line of retinoblastoma. Cancer Inst 53:347–360
29.
go back to reference to hereMcFall RC, Sery TW, Makadon M (1977) Characterization of a new continuous cell line derived from a human retinoblastoma. Cancer Res 37:1003–1010PubMed to hereMcFall RC, Sery TW, Makadon M (1977) Characterization of a new continuous cell line derived from a human retinoblastoma. Cancer Res 37:1003–1010PubMed
30.
go back to reference Jie J, Yuzhen Y, Jianliang Z, Guanguang F, Ruling Z (1991) Establishment and characterization of a human retinoblastoma cell line SO-RB50. Zhong Shan Yi Ke Da Xue Xue Bao [Journal of Sun Yat-sen University] 12:173–177 Jie J, Yuzhen Y, Jianliang Z, Guanguang F, Ruling Z (1991) Establishment and characterization of a human retinoblastoma cell line SO-RB50. Zhong Shan Yi Ke Da Xue Xue Bao [Journal of Sun Yat-sen University] 12:173–177
31.
go back to reference Oltvai ZN, Milliman CM, Korsmeyer SJ (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74:609–619PubMedCrossRef Oltvai ZN, Milliman CM, Korsmeyer SJ (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74:609–619PubMedCrossRef
32.
go back to reference Knudson CM, Tung KS, Tourtellotte WG (1995) Bax-deficient mice with lymphoid hyperplasis and male germ cell death. Science 270:96–99PubMedCrossRef Knudson CM, Tung KS, Tourtellotte WG (1995) Bax-deficient mice with lymphoid hyperplasis and male germ cell death. Science 270:96–99PubMedCrossRef
33.
go back to reference Lovec H, Sewing A, Lucibello FC, Müller R, Möröy T (1994) Oncogenic activity of cyclin D1 revealed through cooperation with Ha-ras: link between cell cycle control and malignant transformation. Oncogene 9:323–326PubMed Lovec H, Sewing A, Lucibello FC, Müller R, Möröy T (1994) Oncogenic activity of cyclin D1 revealed through cooperation with Ha-ras: link between cell cycle control and malignant transformation. Oncogene 9:323–326PubMed
34.
go back to reference Bukholm IK, Nesland JM (2000) Protein expression of p53, p21(WAF1/CIP1), bcl-2, Bax, cyclin D1 and pRb in human colon carcinomas. Virchows Arch 436:224–228PubMedCrossRef Bukholm IK, Nesland JM (2000) Protein expression of p53, p21(WAF1/CIP1), bcl-2, Bax, cyclin D1 and pRb in human colon carcinomas. Virchows Arch 436:224–228PubMedCrossRef
Metadata
Title
Effects of matrine on proliferation and apoptosis of cultured retinoblastoma cells
Authors
Bowen Zhao
Bin Li
Shuwei Bai
Ling Shen
Ruojin Ren
Jost B. Jonas
Xiaolin Xu
Qingjun Lu
Qian Liu
Publication date
01-06-2012
Publisher
Springer-Verlag
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 6/2012
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-011-1751-4

Other articles of this Issue 6/2012

Graefe's Archive for Clinical and Experimental Ophthalmology 6/2012 Go to the issue