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Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

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Article

Atg5 siRNA inhibits autophagy and enhances norcantharidin-induced apoptosis in hepatocellular carcinoma

  • Authors:
    • Xuanxuan Xiong
    • Mingbo Wu
    • Haiyan Zhang
    • Jin Li
    • Bo Lu
    • Yonggao Guo
    • Tian Zhou
    • Hao Guo
    • Rui Peng
    • Xiangcheng Li
    • Qingzhong Tian
    • Yun Wang
  • View Affiliations / Copyright

    Affiliations: Department Of Gastroenterology 2, Xuzhou City Central Hospital, The Affiliated Hospital of the Southeast University Medical School (Xuzhou), Xuzhou, Jiangsu 221009, P.R. China, Department of Oncological Surgery 2, Xuzhou City Central Hospital, The Affiliated Hospital of the Southeast University Medical School (Xuzhou), The Tumor Research Institute of the Southeast University (Xuzhou), Xuzhou, Jiangsu 221009, P.R. China, Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Department of Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
  • Pages: 1321-1328
    |
    Published online on: July 24, 2015
       https://doi.org/10.3892/ijo.2015.3103
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Abstract

Cantharidin is a terpenoid isolated from Chinese blister beetles, and norcantharidin (NCTD) is a demethylated analog of cantharidin. It has been reported that cantharidin and norcantharidin have anticancer activities. Growing evidence suggests that inhibiting autophagy can induce apoptosis in the human hepatoma cell line HepG2. The objective of the present study was to determine whether inhibition of autophagy enhances NCTD-induced apoptosis in HepG2 cells. HepG2 cells were cultured in DMEM containing NCTD. Autophagy was upregulated in the presence of HBSS media supplemented with Ca2+ and Mg2+ and 10 mM HEPES and downregulated in the presence of 3-methyladenine (3-MA) and Atg5 siRNA. Autophagy, cell viability, and the expression of apoptotic proteins were assessed in HepG2 cells. Our data showed that cell apoptosis generally increased after norcantharidin treatment in HepG2 cells. Expression of LC3-II, an autophagosome marker, increased when cells were treated with HBSS media. It also increased cell viability. However, in the presence of 3-MA and Atg5 siRNA, autophagy was inhibited, LC3-II expression decreased and cell apoptosis increased. There was increased expression of Bax, cytochrome c, cleaved caspase-3, caspase-9 and PARP and the mitochondrial membrane potential was disrupted. Additionally, increased apoptosis was accompanied by increased reactive oxygen species (ROS) production. NCTD has anticancer activity, and Atg5 siRNA-mediated downregulation of autophagy enhanced its anticancer actions due to ROS generation and activation of the mitochondrial apoptosis pathway.
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1 

Dubois-Pot-Schneider H, Fekir K, Coulouarn C, Glaise D, Aninat C, Jarnouen K, Le Guével R, Kubo T, Ishida S, Morel F, et al: Inflammatory cytokines promote the retrodifferentiation of tumor-derived hepatocyte-like cells to progenitor cells. Hepatology. 60:2077–2090. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Su YH, Lin SY, Song W and Jain S: DNA markers in molecular diagnostics for hepatocellular carcinoma. Expert Rev Mol Diagn. 14:803–817. 2014. View Article : Google Scholar : PubMed/NCBI

3 

White JA, Redden DT, Bryant MK, Dorn D, Saddekni S, Aal AKA, Zarzour J, Bolus D, Smith JK, Gray S, et al: Predictors of repeat transarterial chemoembolization in the treatment of hepatocellular carcinoma. HPB (Oxford). 16:1095–1101. 2014. View Article : Google Scholar

4 

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar

5 

Bruix J and Sherman M: American Association for the Study of Liver Diseases: Management of hepatocellular carcinoma: An update. Hepatology. 53:1020–1022. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Yeh CH, Yang YY, Huang YF, Chow KC and Chen MF: Induction of apoptosis in human Hep3B hepatoma cells by norcantharidin through a p53 independent pathway via TRAIL/DR5 signal transduction. Chin J Integr Med. 18:676–682. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Han W, Wang S, Liang R, Wang L, Chen M, Li H and Wang Y: Non-ionic surfactant vesicles simultaneously enhance antitumor activity and reduce the toxicity of cantharidin. Int J Nanomed. 8:2187–2196. 2013.

8 

Rautou PE, Mansouri A, Lebrec D, Durand F, Valla D and Moreau R: Autophagy in liver diseases. J Hepatol. 53:1123–1134. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Longo L, Platini F, Scardino A, Alabiso O, Vasapollo G and Tessitore L: Autophagy inhibition enhances anthocyanin-induced apoptosis in hepatocellular carcinoma. Mol Cancer Ther. 7:2476–2485. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Chang C, Zhu YQ, Mei JJ, Liu SQ and Luo J: Involvement of mitochondrial pathway in NCTD-induced cytotoxicity in human hepG2 cells. J Exp Clin Cancer Res. 29:1452010. View Article : Google Scholar : PubMed/NCBI

11 

Settembre C, Di Malta C, Polito VA, Garcia Arencibia M, Vetrini F, Erdin S, Erdin SU, Huynh T, Medina D, Colella P, et al: TFEB links autophagy to lysosomal biogenesis. Science. 332:1429–1433. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Carchman EH, Rao J, Loughran PA, Rosengart MR and Zuckerbraun BS: Heme oxygenase-1-mediated autophagy protects against hepatocyte cell death and hepatic injury from infection/sepsis in mice. Hepatology. 53:2053–2062. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Lewis JS, Meeke K, Osipo C, Ross EA, Kidawi N, Li T, Bell E, Chandel NS and Jordan VC: Intrinsic mechanism of estradiol-induced apoptosis in breast cancer cells resistant to estrogen deprivation. J Natl Cancer Inst. 97:1746–1759. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Jhunjhunwala S, Jiang Z, Stawiski EW, Gnad F, Liu J, Mayba O, Du P, Diao J, Johnson S, Wong KF, et al: Diverse modes of genomic alteration in hepatocellular carcinoma. Genome Biol. 15:4362014.PubMed/NCBI

15 

Yeh CB, Su CJ, Hwang JM and Chou MC: Therapeutic effects of cantharidin analogues without bridging ether oxygen on human hepatocellular carcinoma cells. Eur J Med Chem. 45:3981–3985. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Williams LA, Möller W, Merisor E, Kraus W and Rösner H: In vitro anti-proliferation/cytotoxic activity of cantharidin (Spanish Fly) and related derivatives. West Indian Med J. 52:10–13. 2003.PubMed/NCBI

17 

Xu Y, An Y, Wang Y, Zhang C, Zhang H, Huang C, Jiang H, Wang X and Li X: miR-101 inhibits autophagy and enhances cisplatin-induced apoptosis in hepatocellular carcinoma cells. Oncol Rep. 29:2019–2024. 2013.PubMed/NCBI

18 

Mizushima N, Levine B, Cuervo AM and Klionsky DJ: Autophagy fights disease through cellular self-digestion. Nature. 451:1069–1075. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Xie JM, Li B, Yu HP, Gao QG, Li W, Wu HR and Qin ZH: TIGAR has a dual role in cancer cell survival through regulating apoptosis and autophagy. Cancer Res. 74:5127–5138. 2014. View Article : Google Scholar : PubMed/NCBI

20 

Xie SQ, Zhang YH, Li Q, Xu FH, Miao JW, Zhao J and Wang CJ: 3-Nitro-naphthalimide and nitrogen mustard conjugate NNM-25 induces hepatocellular carcinoma apoptosis via PARP-1/p53 pathway. Apoptosis. 17:725–734. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Qi F, Inagaki Y, Gao B, Cui X, Xu H, Kokudo N, Li A and Tang W: Bufalin and cinobufagin induce apoptosis of human hepatocellular carcinoma cells via Fas- and mitochondria-mediated pathways. Cancer Sci. 102:951–958. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Shen B, He PJ and Shao CL: Norcantharidin induced DU145 cell apoptosis through ROS-mediated mitochondrial dysfunction and energy depletion. PLoS One. 8:e846102013. View Article : Google Scholar : PubMed/NCBI

23 

Kim I and Lemasters JJ: Mitophagy selectively degrades individual damaged mitochondria after photoirradiation. Antioxid Redox Signal. 14:1919–1928. 2011. View Article : Google Scholar :

24 

Zhang R, Humphreys I, Sahu RP, Shi Y and Srivastava SK: In vitro and in vivo induction of apoptosis by capsaicin in pancreatic cancer cells is mediated through ROS generation and mitochondrial death pathway. Apoptosis. 13:1465–1478. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Kang JY, Eggert M, Mouli S, Aljuffali I, Fu X, Nie B, Sheil A, Waddey K, Oldham CD, May SW, et al: Pharmacokinetics, antitumor and cardioprotective effects of liposome-encapsulated phenylaminoethyl selenide in human prostate cancer rodent models. Pharm Res. 32:852–862. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Ott M, Gogvadze V, Orrenius S and Zhivotovsky B: Mitochondria, oxidative stress and cell death. Apoptosis. 12:913–922. 2007. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Xiong X, Wu M, Zhang H, Li J, Lu B, Guo Y, Zhou T, Guo H, Peng R, Li X, Li X, et al: Atg5 siRNA inhibits autophagy and enhances norcantharidin-induced apoptosis in hepatocellular carcinoma . Int J Oncol 47: 1321-1328, 2015.
APA
Xiong, X., Wu, M., Zhang, H., Li, J., Lu, B., Guo, Y. ... Wang, Y. (2015). Atg5 siRNA inhibits autophagy and enhances norcantharidin-induced apoptosis in hepatocellular carcinoma . International Journal of Oncology, 47, 1321-1328. https://doi.org/10.3892/ijo.2015.3103
MLA
Xiong, X., Wu, M., Zhang, H., Li, J., Lu, B., Guo, Y., Zhou, T., Guo, H., Peng, R., Li, X., Tian, Q., Wang, Y."Atg5 siRNA inhibits autophagy and enhances norcantharidin-induced apoptosis in hepatocellular carcinoma ". International Journal of Oncology 47.4 (2015): 1321-1328.
Chicago
Xiong, X., Wu, M., Zhang, H., Li, J., Lu, B., Guo, Y., Zhou, T., Guo, H., Peng, R., Li, X., Tian, Q., Wang, Y."Atg5 siRNA inhibits autophagy and enhances norcantharidin-induced apoptosis in hepatocellular carcinoma ". International Journal of Oncology 47, no. 4 (2015): 1321-1328. https://doi.org/10.3892/ijo.2015.3103
Copy and paste a formatted citation
x
Spandidos Publications style
Xiong X, Wu M, Zhang H, Li J, Lu B, Guo Y, Zhou T, Guo H, Peng R, Li X, Li X, et al: Atg5 siRNA inhibits autophagy and enhances norcantharidin-induced apoptosis in hepatocellular carcinoma . Int J Oncol 47: 1321-1328, 2015.
APA
Xiong, X., Wu, M., Zhang, H., Li, J., Lu, B., Guo, Y. ... Wang, Y. (2015). Atg5 siRNA inhibits autophagy and enhances norcantharidin-induced apoptosis in hepatocellular carcinoma . International Journal of Oncology, 47, 1321-1328. https://doi.org/10.3892/ijo.2015.3103
MLA
Xiong, X., Wu, M., Zhang, H., Li, J., Lu, B., Guo, Y., Zhou, T., Guo, H., Peng, R., Li, X., Tian, Q., Wang, Y."Atg5 siRNA inhibits autophagy and enhances norcantharidin-induced apoptosis in hepatocellular carcinoma ". International Journal of Oncology 47.4 (2015): 1321-1328.
Chicago
Xiong, X., Wu, M., Zhang, H., Li, J., Lu, B., Guo, Y., Zhou, T., Guo, H., Peng, R., Li, X., Tian, Q., Wang, Y."Atg5 siRNA inhibits autophagy and enhances norcantharidin-induced apoptosis in hepatocellular carcinoma ". International Journal of Oncology 47, no. 4 (2015): 1321-1328. https://doi.org/10.3892/ijo.2015.3103
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