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Article

Cytisine induces apoptosis of HepG2 cells

  • Authors:
    • Lei Yu
    • Xin Wang
    • Zhi‑Feng Chen
    • Bo Jiang
    • Dong‑Yu Shang
    • Yong‑Xue Sun
    • Jing‑Hui Yang
    • Lian‑Fang Zhang
    • Yu‑Bin Ji
  • View Affiliations / Copyright

    Affiliations: Center of Research and Development on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin, Heilongjiang 150076, P.R. China
  • Pages: 3363-3370
    |
    Published online on: July 14, 2017
       https://doi.org/10.3892/mmr.2017.6991
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Abstract

Cytisine is a quinolizidine alkaloid, which has been reported to be among the major bioactive components of Sophora alopecuraides L. Quinolizidine alkaloids have previously been demonstrated to inhibit the proliferation of several types of tumor cells. However, few studies have investigated the effects of cytisine on cancer cells. The present study was performed to further investigate the molecular mechanisms underlying cytisine‑induced apoptosis of HepG2 human hepatocellular carcinoma cells. The results of an MTT assay demonstrated that cytisine inhibited the growth of HepG2 cells in a dose‑dependent manner. In addition, the induction of apoptosis was detected, as determined by morphological observation and flow cytometry. As determined by fluorescence microscopy, apoptotic morphological alterations were detected following cytisine administration. Flow cytometric analyses demonstrated that cytisine induced cytotoxicity through apoptosis‑like mechanisms in HepG2 cells. Furthermore, western blot analysis was performed to investigate the release of cytochrome c (Cyt‑c) and activation of the caspase cascade, and the results indicated that treatment of HepG2 cells with cytisine induced caspase‑dependent apoptosis via the release of Cyt‑c from the mitochondria, upregulation of caspase‑3 and downregulation of pro‑caspase‑3. These results indicated that cytisine may induce apoptosis of HepG2 cells through the mitochondrial pathway.
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1 

Rebecca L, Kimberly D and Ahmedin J: Cancer statistics, 2016. A Can J Clin. 66:7–30. 2016. View Article : Google Scholar

2 

Begnini KR, de Moura Leon PM, Thurow H, Schultze E, Campos VF, Martins Rodrigues F, Borsuk S, Dellagostin OA, Savegnago L, Roesch-Ely M, et al: Brazilian red propolis induces apoptosis-like cell death and decreases migration potential in bladder cancer cells. Evid Based Complement Alternat Med. 2014:6398562014. View Article : Google Scholar : PubMed/NCBI

3 

Lin Z, Huang CF, Liu XS and Jiang J: In vitro anti-tumour activities of quinolizidine alkaloids derived from Sophora flavescens Ait. Basic Clin Pharmacol Toxicol. 108:304–309. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Zhou CC, Gao HB, Sun XB, Shi HB, Liu W, Yuan HN and Wang ZX: Anti-inflammatory and anti-allergic action of aloperine. Zhongguo Yao Li Xue Bao. 10:360–365. 1989.PubMed/NCBI

5 

Zhang L, Zheng Y, Deng H, Liang L and Peng J: Aloperine induces G2/M phase cell cycle arrest and apoptosis in HCT116 human colon cancer cells. Int J Mol Med. 33:1613–1620. 2014.PubMed/NCBI

6 

Du M, Zhang J, Xu D, Li W, Liu J and Liu F: Inhibition of pro-collagen I expression by oxymatrine in hepatic stellate cells is mediated via nuclear translocation of Y-box binding protein 1. Mol Med Rep. 12:8101–8106. 2015.PubMed/NCBI

7 

Liang L, Wang XY, Zhang XH, Ji B, Yan HC, Deng HZ and Wu XR: Sophoridine exerts an anti-colorectal carcinoma effect through apoptosis induction in vitro and in vivo. Life Sci. 91:1295–1303. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Wang WX, Sun ZH, Chen HM, Xu BN and Wang FY: Role and mechanism of Sophoridine on proliferation inhibition in human glioma U87MG cell line. Int J Clin Exp Med. 8:464–471. 2015.PubMed/NCBI

9 

Zhu YY, Huang HY and Wu YL: Anticancer and apoptotic activities of oleanolic acid are mediated through cell cycle arrest and disruption of mitochondrial membrane potential in HepG2 human hepatocellular carcinoma cells. Mol Med Rep. 12:5012–5018. 2015.PubMed/NCBI

10 

Luo X, Budihardjo I, Zou H, Slaughter C and Wang X: Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell. 94:481–490. 1998. View Article : Google Scholar : PubMed/NCBI

11 

Marcaurelle LA, Johannes C, Yohannes D, Tillotson BP and Mann D: Diversity-oriented synthesis of a cytisine-inspired pyridone library leading to the discovery of novel inhibitors of Bcl-2. Bioorg Med Chem Lett. 19:2500–2503. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Chellappan SK, Xiao Y, Tueckmantel W, Kellar KJ and Kozikowski AP: Synthesis and pharmacological evaluation of novel 9- and 10-substituted cytisine derivatives. Nicotinic ligands of enhanced subtype selectivity. J Med Chem. 49:2673–2676. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Muslim NS, Ng KW, Itam A, Nassa ZD, Ismail Z and Majid AMS Abdul: Evaluation of cytotoxic, anti-angiogenic and antioxidant properties of standardized extracts of strobilanthes crispus leaves. Int J Pharmacol. 6:591–599. 2010. View Article : Google Scholar

14 

Harpsøe K, Hald H, Timmermann DB, Jensen ML, Dyhring T, Nielsen EØ, Peters D, Balle T, Gajhede M, Kastrup JS and Ahring PK: Molecular determinants of subtype-selective efficacies of cytisine and the novel compound NS3861 at heteromeric nicotinic acetylcholine receptors. J Biol Chem. 288:2559–2570. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Wang H, Yang S, Zhou H, Sun M, Du L, Wei M, Luo M, Huang J, Deng H, Feng Y, et al: Aloperine executes antitumor effects against multiple myeloma through dual apoptotic mechanisms. J Hematol Oncol. 8:262015. View Article : Google Scholar : PubMed/NCBI

16 

Sciamanna MA, Griesmann GE, Williams CL and Lennon VA: Nicotinic acetylcholine receptors of muscle and neuronal (alpha7) types coexpressed in a small cell lung carcinoma. J Neurochem. 69:2302–2311. 1997. View Article : Google Scholar : PubMed/NCBI

17 

Wang J, Fu XQ, Lei WL, Wang T, Sheng AL and Luo ZG: Nuclear factor kappa в controls acetylcholine receptor clustering at the neuromuscular junction. J Neurosci. 30:11104–11113. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Chacko S and Samanta S: Hepatocellular carcinoma: A life-threatening disease. Biomed Pharmacother. 84:1679–1688. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Dickinson BC and Chang CJ: Chemistry and biology of reactive oxygen species in signaling or stress responses. Nat Chem Biol. 7:504–511. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Muchmore SW, Sattler M, Liang H, Meadows RP, Harlan JE, Yoon HS, Nettesheim D, Chang BS, Thompson CB, Wong SL, et al: X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature. 381:335–341. 1996. View Article : Google Scholar : PubMed/NCBI

21 

Carmichael J, DeGraff WG, Gazdar AF, Minna JD and Mitchell JB: Evaluation of a tetrazolium-based semiautomated colorimetric assay: Assessment of chemosensitivity testing. Cancer Res. 47:936–942. 1987.PubMed/NCBI

22 

Araki T, Yamamoto A and Yamada M: Accurate determination of DNA content in single cell nuclei stained with Hoechst 33258 fluorochrome at high salt concentration. Histochemistry. 87:331–338. 1987. View Article : Google Scholar : PubMed/NCBI

23 

Holmquist G: Hoechst 33258 fluorescent staining of Drosophila chromosomes. Chromosoma. 49:333–356. 1975. View Article : Google Scholar : PubMed/NCBI

24 

Wyllie AH, Morris RG, Smith AL and Dunlop D: Chromatin cleavage in apoptosis: Association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol. 142:67–77. 1984. View Article : Google Scholar : PubMed/NCBI

25 

Gong J, Traganos F and Darzynkiewicz Z: A selective procedure for DNA extraction from apoptotic cells applicable for gel electrophoresis and flow cytometry. Anal Biochem. 218:314–319. 1994. View Article : Google Scholar : PubMed/NCBI

26 

Nicoletti I, Migliorati G, Pagliacci MC, Grignani F and Riccardi C: A rapid simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods. 139:271–279. 1991. View Article : Google Scholar : PubMed/NCBI

27 

Basiji DA, Ortyn WE, Liang L, Venkatachalam V and Morrissey P: Cellular image analysis and imaging by flow cytometry. Clin Lab Med. 27:653–670, viii. 2007. View Article : Google Scholar : PubMed/NCBI

28 

Scaduto RC Jr and Grotyohann LW: Measurement of mitochondrial membrane potential using fluorescent rhodamine derivatives. Biophys J. 76:469–477. 1999. View Article : Google Scholar : PubMed/NCBI

29 

Ashley RL, Militoni J, Lee F, Nahmias A and Corey L: Comparison of Western blot (immunoblot) and glycoprotein G-specific immunodot enzyme assay for detecting antibodies to herpes simplex virus types 1 and 2 in human sera. J Clin Microbiol. 26:662–667. 1988.PubMed/NCBI

30 

Zhang H, Xiong Z, Wang J, Zhang SS, Lei L, Yang L and Zhang Z: Glucagon-like peptide-1 protects cardiomyocytes from advanced oxidation protein product-induced apoptosis via the PI3K/Akt/Bad signaling pathway. Mol Med Rep. 13:1593–1601. 2016.PubMed/NCBI

31 

Kim KN, Ham YM, Moon JY, Kim MJ, Kim DS, Lee WJ, Lee NH and Hyun CG: In vitro cytotoxic activity of sargassum thunbergii and dictyopteris divaricata (Jeju Seaweeds) on the HL-60 tumour cell line. Int J Pharmacol. 5:298–306. 2009. View Article : Google Scholar

32 

Oh HL, Lee DK, Lim H and Lee CH: HY253, a novel decahydrofluorene analog, from Aralia continentalis, induces cell cycle arrest at the G1 phase and Cyt-C-mediated apoptosis in human lung cancer A549 cells. J Ethnopharmacol. 129:135–139. 2010. View Article : Google Scholar : PubMed/NCBI

33 

Darzynkiewicz Z, Juan G, Li X, Gorczyca W, Murakami T and Traganos F: Cytometry in cell necrobiology: Analysis of apoptosis and accidental cell death (necrosis). Cytom. 27:1–20. 1997. View Article : Google Scholar

34 

Hwang MW and Kim BJ: Apoptotic effects and involvement of TRPM7 channels of the traditional herbal medicine, dangkwisoo-san in gastric cancer cells. Int J Pharmacol. 10:398–405. 2014. View Article : Google Scholar

35 

Gazaliev AM, Zhurinov MZ and Tuleuov BI: Isolation, analysis, biosynthesis, and modification of the alkaloid cytisine. Chem Nat Com. 27:259–269. 1991. View Article : Google Scholar

36 

Scorrano L: Opening the doors to cytochrome c: Changes in mitochondrial shape and apoptosis. Int J Biochem Cell Biol. 41:1875–1883. 2009. View Article : Google Scholar : PubMed/NCBI

37 

Rouhollahi E, Moghadamtousi S Zorofchian, Paydar M, Fadaeinasab M, Zahedifard M, Hajrezaie M, Hamdi OA Ahmed, Looi CY, Abdulla MA, Awang K and Mohamed Z: Inhibitory effect of Curcuma purpurascens BI. rhizome on HT-29 colon cancer cells through mitochondrial-dependent apoptosis pathway. BMC Complement Altern Med. 15:152015. View Article : Google Scholar : PubMed/NCBI

38 

Philchenkov AA: Caspases as regulators of apoptosis and other cell functions. Biochem (Mosc). 68:365–376. 2003. View Article : Google Scholar

39 

Riedl SJ and Shi Y: Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Bio. 5:897–907. 2004. View Article : Google Scholar

40 

Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW and Yuan J: Human ICE/CED-3 protease nomenclature. Cell. 87:1711996. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yu L, Wang X, Chen ZF, Jiang B, Shang DY, Sun YX, Yang JH, Zhang LF and Ji YB: Cytisine induces apoptosis of HepG2 cells. Mol Med Rep 16: 3363-3370, 2017.
APA
Yu, L., Wang, X., Chen, Z., Jiang, B., Shang, D., Sun, Y. ... Ji, Y. (2017). Cytisine induces apoptosis of HepG2 cells. Molecular Medicine Reports, 16, 3363-3370. https://doi.org/10.3892/mmr.2017.6991
MLA
Yu, L., Wang, X., Chen, Z., Jiang, B., Shang, D., Sun, Y., Yang, J., Zhang, L., Ji, Y."Cytisine induces apoptosis of HepG2 cells". Molecular Medicine Reports 16.3 (2017): 3363-3370.
Chicago
Yu, L., Wang, X., Chen, Z., Jiang, B., Shang, D., Sun, Y., Yang, J., Zhang, L., Ji, Y."Cytisine induces apoptosis of HepG2 cells". Molecular Medicine Reports 16, no. 3 (2017): 3363-3370. https://doi.org/10.3892/mmr.2017.6991
Copy and paste a formatted citation
x
Spandidos Publications style
Yu L, Wang X, Chen ZF, Jiang B, Shang DY, Sun YX, Yang JH, Zhang LF and Ji YB: Cytisine induces apoptosis of HepG2 cells. Mol Med Rep 16: 3363-3370, 2017.
APA
Yu, L., Wang, X., Chen, Z., Jiang, B., Shang, D., Sun, Y. ... Ji, Y. (2017). Cytisine induces apoptosis of HepG2 cells. Molecular Medicine Reports, 16, 3363-3370. https://doi.org/10.3892/mmr.2017.6991
MLA
Yu, L., Wang, X., Chen, Z., Jiang, B., Shang, D., Sun, Y., Yang, J., Zhang, L., Ji, Y."Cytisine induces apoptosis of HepG2 cells". Molecular Medicine Reports 16.3 (2017): 3363-3370.
Chicago
Yu, L., Wang, X., Chen, Z., Jiang, B., Shang, D., Sun, Y., Yang, J., Zhang, L., Ji, Y."Cytisine induces apoptosis of HepG2 cells". Molecular Medicine Reports 16, no. 3 (2017): 3363-3370. https://doi.org/10.3892/mmr.2017.6991
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