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Induction of human chronic myeloid leukemia K562 cell apoptosis by virosecurinine and its molecular mechanism

  • Authors:
    • Gang Zhang
    • Maidong Li
    • Shuwen Han
    • Dongyun Chen
    • Ying Wang
    • Wencai Ye
    • Zhaoning Ji
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Wannan Medical College, Wuhu, Anhui 241001, P.R. China, Department of Medical Oncology, The Cancer Center, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China, Department of Pharmacy, Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou, Guangdong 510632, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 2365-2371
    |
    Published online on: September 3, 2014
       https://doi.org/10.3892/mmr.2014.2531
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Abstract

Virosecurinine is a major alkaloid of the plant Securinega suffruticosa and has been found to be a potent agent in inducing the differentiation of cancer cells. The present study aimed to investigate the antitumor effects of virosecurinine by inducing the apoptosis of leukemic K562 cells and to examine the underlying mechanisms. K562 cells were treated with different concentrations of virosecurinine (6.25, 12.5, 25, 50, 100 and 200 µmol/l) for 24, 48 and 72 h. The cell counting kit (CCK)‑8 method was used to detect the antitumor effect of K562 cells in vitro. Flow cytometry was used to observe the apoptotic ratio and analyze the cell cycle following treatment with virosecurinine in K562 cells. Light and electron microscopy was used to identify morphological alterations in the virosecurinine‑treated K562 cells. The mRNA levels of mammalian target of rapamycin (mTOR), SH2 domain‑containing inositol‑5'‑phosphatase 2 (SHIP2), phosphatase and tensin homologue (PTEN) and breakpoint cluster region (BCR)/Abelson (ABL) were detected pre and post‑virosecurinine treatment using reverse transcription quantitative polymerase chain reaction (RT‑qPCR). The generation depression effects of K562 cells cultured in vitro were detected using CCK‑8 technology, which revealed a dose and time‑dependent association. The IC50 was 32.984 µmol/l at 48 h. Flow cytometric analysis indicated that treatment with virosecurinine at concentrations of 6.25, 25 and 50 µmol/l increased the apoptotic rate of the K562 cells and caused G1/S phase arrest. RT‑qPCR indicated that virosecurinine upregulated the gene expression of PTEN and downregulated the expression of mTOR, SHIP‑2 and BCR/ABL in K562 cells. Virosecurinine inhibited the growth and proliferation of the K562 cell lines and induced apoptosis in K562 cells by affecting the expression of mTOR, SHIP2, BCR/ABL and PTEN.
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1 

Deininger MW, Goldman JM and Melo JV: The molecular biology of chronic myeloid leukemia. Blood. 96:3343–3356. 2000.PubMed/NCBI

2 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Cancer statistics, 2009. CA Cancer J Clin. 59:225–249. 2009. View Article : Google Scholar

3 

Lin H and Chen ZL: Progress of researching in anti-tumor drugs. Chin J Hosp Pharm. 8:226–228. 1998.(In Chinese).

4 

Saito S, Kotera K, Shigematsu N, Ide A, Sugimoto N, Horii Z, et al: Structure of securinine. Tetrahedron. 19:2085–2099. 1963. View Article : Google Scholar : PubMed/NCBI

5 

Beutler JA, Karbon EW, Brubaker AN, Malik R, Curtis DR and Enna SJ: Securinine alkaloids: a new class of GABA receptor antagonist. Brain Res. 330:135–140. 1985. View Article : Google Scholar : PubMed/NCBI

6 

Weenen H, Nkunya MH, Bray DH, Mwasumbi LB, Kinabo LS, Kilimali VA, et al: Antimalarial compounds containing an alpha, beta-unsaturated carbonyl moiety from Tanzanian medicinal plants. Planta Med. 56:371–373. 1990. View Article : Google Scholar : PubMed/NCBI

7 

Mensah JL, Lagarde I, Ceschin C, Michel G, Gleye J and Fouraste I: Antibacterial activity of the leaves of Phyllanthus discoideus. J Ethnopharmacol. 28:129–133. 1990. View Article : Google Scholar : PubMed/NCBI

8 

Dong NZ and Gu ZL: Study on the antitumor effect of securinine and its mechanism. Chin Tradit Pat Med. 21:193–195. 1999.(In Chinese).

9 

Jiang XY: The effect of securinine and aminophylline on hemopoietic stem cells and granulopoietic progenitors in mice. Tianjin Med J. 10:99–100. 1982.(In Chinese).

10 

Liu WJ, Gu ZL and Zhou WX: Securinine induced apoptosis in K562 cells. Chin Pharmacol Bull. 115:135–158. 1999.

11 

Pérez JM, Quiroga AG, Montero EI, Alonso C and Navarro-Ranninger C: A cycloplatinated compound of p-isopropylbenzaldehyde thiosemicarbazone and its chloro-bridged derivative induce apoptosis in cis-DDP resistant cells which overexpress the H-ras oncogene. J Inorg Biochem. 73:235–243. 1999.

12 

Kerr JF, Wyllie AH and Currie AR: Apoptosis: a basic biological phenomenon with wide ranging implications in tissue kinetics. Br J Cancer. 26:239–257. 1972. View Article : Google Scholar : PubMed/NCBI

13 

Steller H: Mechanisms and genes of cellular suicide. Science. 267:1445–1449. 1995. View Article : Google Scholar : PubMed/NCBI

14 

Hector S, Rehm M, Schmid J, Kehoe J, McCawley N, Dicker P, et al: Clinical application of a systems model of apoptosis execution for the prediction of colorectal cancer therapy responses and personalisation of therapy. Gut. 11:725–733. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Huber HJ, Dussmann H, Kilbride SM, Rehm M and Prehn JH: Glucose metabolism determines resistance of cancer cells to bioenergetic crisis after cytochrome-c release. Mol Syst Biol. 7:4702011. View Article : Google Scholar

16 

Lee MJ, Ye AS, Gardino AK, Heijink AM, Sorger PK, MacBeath G and Yaffe MB: Sequential application of anticancer drugs enhances cell death by rewiring apoptotic signaling networks. Cell. 149:780–794. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Hay N and Sonenberg N: Upstream and downstream of mTOR. Genes Dev. 18:1926–1945. 2001. View Article : Google Scholar

18 

Montiel-Duarte C, Cordeu L, Agirre X, Román-Gómez J, Jiménez-Velasco A, José-Eneriz ES, et al: Resistance to Imatinib Mesylate-induced apoptosis in acute lymphoblastic leukemia is associated with PTEN down-regulation due to promoter hypermethylation. Leuk Res. 32:709–716. 2008. View Article : Google Scholar

19 

Wiencke JK, Zheng S, Jelluma N, Tihan T, Vandenberg S, Tamgüney T, et al: Methylation of the PTEN promoter defines low-grade gliomas and secondary glioblastoma. Neuro Oncol. 9:271–279. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Mirmohammadsadegh A, Marini A, Nambiar S, Hassan M, Tannapfel A, Ruzicka T, et al: Epigenetic silencing of the PTEN gene in melanoma. Cancer Res. 66:6546–6552. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Noro R, Gemma A, Miyanaga A, Kosaihira S, Minegishi Y, Nara M, et al: PTEN inactivation in lung cancer cells and the effect of its recovery on treatment with epidermal growth factor receptor tyrosine kinase inhibitors. Int J Oncol. 31:1157–1163. 2007.PubMed/NCBI

22 

Athanassiadou P, Athanassiades P, Grapsa D, Gonidi M, Athanassiadou AM, Stamati PN and Patsouris E: The prognostic value of PTEN, p53, and beta-catenin in endometrial carcinoma: a prospective immunocytochemical study. Int J Gynecol Cancer. 17:697–704. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Goldman JM and Melo JV: BCR-ABL in chronic myelogenous leukemia-how does it work? Acta Haematol. 13:212–217. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C, et al: Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 346:645–652. 2002. View Article : Google Scholar : PubMed/NCBI

25 

Ooms LM, Horan KA, Rahman P, Seaton G, Gurung R, Kethesparan DS and Mitchell CA: The role of the inositol polyphosphate 5-phosphatases in cellular function and human disease. Biochem J. 419:29–49. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Suwa A, Kurama T and Shimokawa T: HIP2 and its involvement in various diseases. Expert Opin Ther Targets. 14:727–737. 2010. View Article : Google Scholar

27 

Suwa A, Yamamoto T, Sawada A, Minoura K, Hosogai N, Tahara A, et al: Discovery and functional characterization of a novel small molecule inhibitor of the intracellular phosphatase, SHIP2. J Pharmacol. 158:879–887. 2009.PubMed/NCBI

28 

Fuhler GM, Brooks R, Toms B, Iyer S, Gengo EA, Park MY, et al: Therapeutic potential of SH2 domain-containing inositol-5′-phosphatase 1 (SHIP1) and SHIP2 inhibition in cancer. Mol Med. 18:65–75. 2012.

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Copy and paste a formatted citation
Spandidos Publications style
Zhang G, Li M, Han S, Chen D, Wang Y, Ye W and Ji Z: Induction of human chronic myeloid leukemia K562 cell apoptosis by virosecurinine and its molecular mechanism. Mol Med Rep 10: 2365-2371, 2014.
APA
Zhang, G., Li, M., Han, S., Chen, D., Wang, Y., Ye, W., & Ji, Z. (2014). Induction of human chronic myeloid leukemia K562 cell apoptosis by virosecurinine and its molecular mechanism. Molecular Medicine Reports, 10, 2365-2371. https://doi.org/10.3892/mmr.2014.2531
MLA
Zhang, G., Li, M., Han, S., Chen, D., Wang, Y., Ye, W., Ji, Z."Induction of human chronic myeloid leukemia K562 cell apoptosis by virosecurinine and its molecular mechanism". Molecular Medicine Reports 10.5 (2014): 2365-2371.
Chicago
Zhang, G., Li, M., Han, S., Chen, D., Wang, Y., Ye, W., Ji, Z."Induction of human chronic myeloid leukemia K562 cell apoptosis by virosecurinine and its molecular mechanism". Molecular Medicine Reports 10, no. 5 (2014): 2365-2371. https://doi.org/10.3892/mmr.2014.2531
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang G, Li M, Han S, Chen D, Wang Y, Ye W and Ji Z: Induction of human chronic myeloid leukemia K562 cell apoptosis by virosecurinine and its molecular mechanism. Mol Med Rep 10: 2365-2371, 2014.
APA
Zhang, G., Li, M., Han, S., Chen, D., Wang, Y., Ye, W., & Ji, Z. (2014). Induction of human chronic myeloid leukemia K562 cell apoptosis by virosecurinine and its molecular mechanism. Molecular Medicine Reports, 10, 2365-2371. https://doi.org/10.3892/mmr.2014.2531
MLA
Zhang, G., Li, M., Han, S., Chen, D., Wang, Y., Ye, W., Ji, Z."Induction of human chronic myeloid leukemia K562 cell apoptosis by virosecurinine and its molecular mechanism". Molecular Medicine Reports 10.5 (2014): 2365-2371.
Chicago
Zhang, G., Li, M., Han, S., Chen, D., Wang, Y., Ye, W., Ji, Z."Induction of human chronic myeloid leukemia K562 cell apoptosis by virosecurinine and its molecular mechanism". Molecular Medicine Reports 10, no. 5 (2014): 2365-2371. https://doi.org/10.3892/mmr.2014.2531
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