Skip to main content
SpringerLink
Log in

Inhibition of matrine against gastric cancer cell line MNK45 growth and its anti-tumor mechanism

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Anti-tumor activity and mechanism of matrine is evaluated and investigated. MTT assay showed that the matrine was able to inhibit gastric cancer cell line MNK45 in a dose-dependent manner. The concentration required for 50% inhibition (IC50) was found to be 540 μg/ml. This anti-tumor function was achieved through modulation of the NF-κB, XIAP, CIAP, and p-ERK proteins expression in cell line MNK45. By western blot analysis, we found that expression of NF-κB, XIAP, CIAP, and p-ERK proteins in cell line MNK45 would vary with varying concentration of matrine. These protein interactions possibly play a pivotal role in the regulation of apoptosis, for which further detailed analyzes are need. These results overall indicate that matrine can be used as an effective anti-tumor agent in therapy of gastric cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A (2005) Cancer statistics. CA Cancer J Clin 55(1):10–30

    Google Scholar 

  2. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics. CA Cancer J Clin 55(2):74–108

    Google Scholar 

  3. Strumylaite L, Zickute J, Dudzevicius J, Dregval L (2006) Salt-preserved foods and risk of gastric cancer. Medicina 42(2):164–170

    PubMed  Google Scholar 

  4. Hu ZL, Zhang JP, Qian DH, Lin W, Xie WF, Zhang XR 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 17:259–261

    PubMed  CAS  Google Scholar 

  5. Chang MS, Xiao JG, Chiou GC (1991) Prevention of ocular inflammation by matrine, prednisolone, and cyclooxygenase and lipoxygenase inhibitors. Zhongguo Yao Li Xue Bao 12:121–125

    PubMed  CAS  Google Scholar 

  6. Tan HR, Zhang BH (1985) Experimental study of the anti-inflammatory effect of matrine. Zhong Xi Yi Jie He Za Zhi 5:108–109

    PubMed  CAS  Google Scholar 

  7. Luo YX, Zhang XM, Gao W, Wu QF (2001) Studies on site of analgesic action of matrine and its mechanism. Zhong Cao Yao 32:41–43

    CAS  Google Scholar 

  8. Xu CQ, Dong DL, Du ZM, Chen QW, Gong DM, Yang BF (2004) Comparison of the anti-arrhythmic effects of matrine and berbamine with amiodarone and RP58866. Yao Xue Xue Bao 39:691–694

    PubMed  CAS  Google Scholar 

  9. Zhang BH, Wang NS, Li XJ, Kong XJ, Cai YL (1990) Anti-arrhythmic effects of matrine. Zhongguo Yao Li Xue Bao 11:253–257

    PubMed  CAS  Google Scholar 

  10. Deng H, Luo H, Huang F, Li X, Gao Q (2004) Inhibition of proliferation and influence of proto-oncogenes expression by matrine in C6 cell. Zhong Yao Cai 27:416–419

    PubMed  Google Scholar 

  11. Zhang YQ, Huang GS, Wang Z, Guo Y, Zhang HY (2001) Effects of matrine on the relative molecules expression of proliferation and apoptosis in K562 cells. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 23:333–336

    PubMed  CAS  Google Scholar 

  12. Zhang JP, Zhang M, Jin C, Zhou B, Xie WF, Guo C et al (2001) Matrine inhibits production and actions of fibrogenic cytokines released by mouse peritoneal macrophages. Acta Pharmacol Sin 22:765–768

    PubMed  CAS  Google Scholar 

  13. Xin SM, Ma ZQ (1998) Anti-diarrhea effect of matrine. Zhong Cheng Yao 20(1998):30–32

    Google Scholar 

  14. Pei RJ, Xiao L, Fan XP, Liu XJ (1998) The effects of matrine on mouse immune functions. Hai Xia Yao Xue 10:7–8

    Google Scholar 

  15. Ghosh S, May MJ, Kopp EB (1998) NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol 16:225–260

    Article  PubMed  CAS  Google Scholar 

  16. Hacker H, Karin M (2006) Regulation and function of IKK and IKK-related kinases. Sci STKE: re13

  17. Meffert MK, Baltimore D (2005) Physiological functions for brain NF-kappaB. Trends Neurosci 28:37–43

    Article  PubMed  CAS  Google Scholar 

  18. Ballard DW, Dixon EP, Peffer NJ, Bogerd H, Doerre S, Stein B, Greene WC (1992) The 65-kDa subunit of human NF-κB functions as a potent transcriptional activator and a target for v-Rel-mediated repression. Proc Natl Acad Sci USA 89:1875–1879

    Article  PubMed  CAS  Google Scholar 

  19. Ruben SM, Narayanan ML, Klement JF, Chen C-H, Rosen CA (1992) Functional characterization of the NF-κB p65 transcriptional activator and an alternatively spliced derivative. Mol Cell Biol 12:444–454

    PubMed  CAS  Google Scholar 

  20. Jobin C, Haskill S, Mayer L, Panja A, Sartor RB (1997) Evidence for an altered regulation of IκBα degradation in human colonic epithelial cells. J Immunol 158:226–234

    PubMed  CAS  Google Scholar 

  21. Jobin C, Holt L, Bradham CA, Streetz K, Brenner DA, Sartor RB (1999) TRAF-2 is involved in both IL-1β and TNFα-signaling cascade leading to NF-κB activation and IL-8 expression in human intestinal epithelial cells. J Immunol 162:4447–4454

    PubMed  CAS  Google Scholar 

  22. Baeuerle PA, Henkle T (1994) Function and activation of NF-κB in the immune system. Annu Rev Immunol 12:141–179

    Article  PubMed  CAS  Google Scholar 

  23. Barnes PJ, Karin M (1997) Nuclear factor-κB, a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336:1066–1071

    Article  PubMed  CAS  Google Scholar 

  24. Anest V, Hanson J, Cogswell P, Steinbrecher K, Strahl B, Baldwin A (2003) A nucleosomal function for IκB kinase-α in NF-κB-dependent gene expression. Nature 423:659–663

    Article  PubMed  CAS  Google Scholar 

  25. Yamamoto Y, Verma U, Prajapati S, Kwak Y-T, Gaynor R (2003) Histone H3 phosphorylation by IKK-α is critical for cytokine-induced gene expression. Nature 423:655–659

    Article  PubMed  CAS  Google Scholar 

  26. Gilmore TD (2006) Introduction to NF-κB: players, pathways, perspectives. Oncogene 25(51):6680–6684

    Article  PubMed  CAS  Google Scholar 

  27. Brasier AR (2006) The NF-κB regulatory network. Cardiovasc Toxicol 6(2):111–130

    Article  PubMed  CAS  Google Scholar 

  28. Perkins ND (2007) Integrating cell-signalling pathways with NF-κB and IKK function. Natl Rev Mol Cell Biol 8(1):49–62

    Article  CAS  Google Scholar 

  29. Gilmore TD (1999) The Rel/NF-κB signal transduction pathway: introduction. Oncogene 18(49):6842–6844

    Article  PubMed  CAS  Google Scholar 

  30. Tian B, Brasier AR (2003) Identification of a nuclear factor κB-dependent gene network. Recent Prog Horm Res 58:95–130

    Article  PubMed  CAS  Google Scholar 

  31. Albensi BC, Mattson MP (2000) Evidence for the involvement of TNF and NF-κB in hippocampal synaptic plasticity. Synapse 35(2):151–159

    Article  PubMed  CAS  Google Scholar 

  32. Meffert MK, Chang JM, Wiltgen BJ, Fanselow MS, Baltimore D (2003) NF-kappa B functions in synaptic signaling and behavior. Nat Neurosci 6(10):1072–1078

    Article  PubMed  CAS  Google Scholar 

  33. Levenson JM, Choi S, Lee SY, Cao YA, Ahn HJ, Worley KC, Pizzi M, Liou HC, Sweatt JD (2004) A bioinformatics analysis of memory consolidation reveals involvement of the transcription factor c-rel. J Neurosci 24(16):3933–3943

    Article  PubMed  CAS  Google Scholar 

  34. Freudenthal R, Locatelli F, Hermitte G, Maldonado H, Lafourcade C, Delorenzi A, Romano A (1998) Kappa-B like DNA-binding activity is enhanced after spaced training that induces long-term memory in the crab Chasmagnathus. Neurosci Lett 242(3):143–146

    Article  PubMed  CAS  Google Scholar 

  35. Merlo E, Freudenthal R, Romano A (2002) The IkappaB kinase inhibitor sulfasalazine impairs long-term memory in the crab Chasmagnathus. Neuroscience 112(1):161–172

    Article  PubMed  CAS  Google Scholar 

  36. Byun D-S, Cho K, Ryu B-K, Lee M-G, Kang M-J, Kim H-R, Chi S-G (2003) Hypermethylation of XIAP-associated factor 1, a putative tumor suppressor gene from the 17p13.2 locus, in human gastric adenocarcinomas. Cancer Res 63:7068

    PubMed  CAS  Google Scholar 

  37. Fandy TE, Shankar S, Ross DD, Sausville E, Srivastava RK (2005) Interactive effects of HDAC inhibitors and trail on apoptosis are associated with changes in mitochondrial functions and expressions of cell cycle regulatory genes in multiple myeloma. Neoplasia 7(7):646–657

    Article  PubMed  CAS  Google Scholar 

  38. Endo K, Kohnoe S, Tsujita E, Watanabe A, Nakashima H, Baba H, Maehara Y (2005) Modulation of anti-apoptosis by endogenous IAP expression in MKN45 human gastric cancer cells. Anticancer Res 25:2713–2718

    PubMed  CAS  Google Scholar 

  39. Deveraux QL, Roy N, Stennicke HR, Van Arsdale T, Zhou Q, Srinivasula SM, Alnemri ES, Salvesen GS, Reed JC (1998) IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J 17:2215–2223

    Article  PubMed  CAS  Google Scholar 

  40. Deveraux QL, Takahashi R, Salvesen GS, Reed JC (1997) X-linked IAP is a direct inhibitor of cell-death proteases. Nature 388:300–304

    Article  PubMed  CAS  Google Scholar 

  41. Roy N, Deveraux QL, Takahashi R, Salvesen GS, Reed JC (1997) The cIAP1 and cIAP2 proteins are distinct inhibitors of specific caspases. EMBO J 16:6914–6925

    Article  PubMed  CAS  Google Scholar 

  42. Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin ASJR (1998) NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 281:1680–1683

    Google Scholar 

  43. Tamm I, Wang Y, Sausville E, Scudiero DA, Vigna N, Oltersdorf T, Reed JC (1998) IAP–family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res 58:5315–5320

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Authors thank all medical workers of chemotherapy center in the 14th Inpatient area of Zhejiang Cancer Hospital for their encouragement and help. This work is supported by the fund from department of health of Zhejiang province (2011KYB023). We are grateful for financial supports by the joint project of Zhejiang Province and Ministry of Health (Grant No WKJ20092024 to HJ), Zhejiang Provincial Natural Science Foundation of China (Grant No. Z2100366 to HJ and J20091440 to XG Wu), 151 Talent Project of Zhejiang Province (HJ), and Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents (HJ).

Author information

Authors and Affiliations

  1. Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 310022, China

    Cong Luo, Hai Jun Zhong, Li Ming Zhu, Jie Er Ying, Xiao Hong Wang, Wang Xia LÜ & Qi Xu

  2. Department of Clinical Laboratory, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, China

    Xian Guo Wu

  3. Department of Gastroenterology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Yong Liang Zhu

  4. Cancer Institute, Department of Oncology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China

    Jian Huang

Authors
  1. Cong Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hai Jun Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Li Ming Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xian Guo Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jie Er Ying
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiao Hong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wang Xia LÜ
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Qi Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yong Liang Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jian Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jian Huang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Luo, C., Zhong, H.J., Zhu, L.M. et al. Inhibition of matrine against gastric cancer cell line MNK45 growth and its anti-tumor mechanism. Mol Biol Rep 39, 5459–5464 (2012). https://doi.org/10.1007/s11033-011-1346-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-011-1346-5

Keywords

Search

Navigation