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Article

Fatsioside A inhibits the growth of glioma cells via the induction of endoplasmic reticulum stress-mediated apoptosis

  • Authors:
    • Ji‑Ming Pan
    • Lu Zhou
    • Guang‑Bin Wang
    • Guang‑Wen Xia
    • Kun  Xue
    • Xin‑Guo Cui
    • Hong‑Zhi Shi
    • Jian‑Hui Liu
    • Jia Hu
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China, Clinical Laboratory, Yantai Hospital of Traditional Chinese Medicine, Yantai, Shandong 264000, P.R. China
  • Pages: 3493-3498
    |
    Published online on: January 16, 2015
       https://doi.org/10.3892/mmr.2015.3213
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Abstract

Malignant gliomas are a common type of primary tumor of the central nervous system. In spite of current intensive therapy, the prognosis of patients with malignant glioma remains poor, hence the development of novel therapeutic modalities is necessary. Cell apoptosis is a frequent target in the development of anti‑cancer drugs. Fatsioside A, a novel baccharane‑type triterpenoid glycoside, is extracted from the fruits of Fatsia japonica. Previous studies have shown that Fatsioside A induces growth inhibition, cell cycle arrest and apoptosis in C6 rat glioma cells and U251 human glioma cells. However, to the best of our knowledge, no detailed studies have reported its effect on U87MG glioma cells and its exact mechanisms remain unknown. In the current study, the growth inhibitory effect of Fatsioside A on U87MG cells was evaluated and the underlying molecular mechanisms were explored. Through the use of flow cytometry and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, it was determined that Fatsioside A markedly inhibits the growth of U87MG cells. Mechanistic studies demonstrated that Fatsioside A induces growth inhibition of U87MG cells via the induction of endoplasmic reticulum (ER) stress, which was supported by the upregulation of ER stress markers, including elevated levels of phosphorylation of PERK and eIF2α, the increased expression levels of CHOP and the accelerated cleavage of caspase‑4. The downregulation of CHOP via CHOP‑specific siRNA reduced the growth‑inhibitive effect of Fatsioside A on U87MG cells, further confirming the role of the ER stress response in mediating Fatsioside A‑induced growth inhibition. In conclusion, Fatsioside A inhibits glioma cell growth via the induction of ER stress‑mediated apoptosis. This may provide a molecular basis for the development of Fatsioside A into a drug candidate for the treatment of malignant glioma.
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View References

1 

Behin A, Hoang-Xuan K, Carpentier AF and Delattre JY: Primary brain tumours in adults. Lancet. 361:323–331. 2003. View Article : Google Scholar : PubMed/NCBI

2 

Bruna A, Darken RS, Rojo F, et al: High TGFbeta-Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene. Cancer Cell. 11:147–160. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Furnari FB, Fenton T, Bachoo RM, et al: Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev. 21:2683–2710. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Hannun YA: Apoptosis and the dilemma of cancer chemotherapy. Blood. 89:1845–1853. 1997.PubMed/NCBI

5 

El-Aneed A: Current strategies in cancer gene therapy. Eur J Pharmacol. 498:1–8. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Evan GI and Vousden KH: Proliferation, cell cycle and apoptosis in cancer. Nature. 411:342–348. 2001. View Article : Google Scholar : PubMed/NCBI

7 

Ellgaard L and Helenius A: Quality control in the endoplasmic reticulum. Nat Rev Mol Cell Biol. 4:181–191. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Sitia R and Braakman I: Quality control in the endoplasmic reticulum protein factory. Nature. 426:891–894. 2003. View Article : Google Scholar : PubMed/NCBI

9 

Rao RV, Ellerby HM and Bredesen DE: Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ. 11:372–380. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Zhang K and Kaufman RJ: From endoplasmic-reticulum stress to the inflammatory response. Nature. 454:455–462. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Malhotra JD and Kaufman RJ: The endoplasmic reticulum and the unfolded protein response. Semin Cell Dev Biol. 18:716–731. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Oyadomari S and Mori M: Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ. 11:381–389. 2004. View Article : Google Scholar

13 

Marciniak SJ, Yun CY, Oyadomari S, et al: CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev. 18:3066–3077. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Salazar M, Carracedo A, Salanueva IJ, et al: Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J Clin Invest. 119:1359–1372. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Carracedo A, Gironella M, Lorente M, et al: Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes. Cancer Res. 66:6748–6755. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Pyrko P, Kardosh A, Wang W, Xiong W, Schönthal AH and Chen TC: HIV-1 protease inhibitors nelfinavir and atazanavir induce malignant glioma death by triggering endoplasmic reticulum stress. Cancer Res. 67:10920–10928. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Tiwari M, Kumar A, Sinha RA, et al: Mechanism of 4-HPR-induced apoptosis in glioma cells: evidences suggesting role of mitochondrial-mediated pathway and endoplasmic reticulum stress. Carcinogenesis. 27:2047–2058. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Yu S, Ye X, Xin W, Xu K, Lian XY and Zhang Z: Fatsioside A, a rare baccharane-type glycoside inhibiting the growth of glioma cells from the fruits of Fatsia japonica. Planta Med. 80:315–320. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Kemertelidze É, Kemoklidze Z, Dekanosidze G and Bereznyakova A: Isolation and pharmacological characterization of triterpenoid glycosides from Fatsia japonica cultivated in Georgia. Pharm Chem J. 35:429–432. 2001. View Article : Google Scholar

20 

Lin SS, Huang HP, Yang JS, et al: DNA damage and endoplasmic reticulum stress mediated curcumin-induced cell cycle arrest and apoptosis in human lung carcinoma A-549 cells through the activation caspases cascade- and mitochondrial-dependent pathway. Cancer Lett. 272:77–90. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Lu JJ, Chen SM, Zhang XW, Ding J and Meng LH: The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells. Invest New Drugs. 29:1276–1283. 2011. View Article : Google Scholar

22 

Tabas I and Ron D: Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol. 13:184–190. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Puthalakath H, O’Reilly LA, Gunn P, et al: ER stress triggers apoptosis by activating BH3-only protein Bim. Cell. 129:1337–1349. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Oyadomari S, Araki E and Mori M: Endoplasmic reticulum stress-mediated apoptosis in pancreatic beta-cells. Apoptosis. 7:335–345. 2002. View Article : Google Scholar : PubMed/NCBI

25 

Pulkkanen KJ and Yla-Herttuala S: Gene therapy for malignant glioma: current clinical status. Mol Ther. 12:585–598. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Okada H, Lieberman FS, Edington HD, et al: Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of recurrent glioblastoma: preliminary observations in a patient with a favorable response to therapy. J Neurooncol. 64:13–20. 2003. View Article : Google Scholar : PubMed/NCBI

27 

Lefranc F, Brotchi J and Kiss R: Possible future issues in the treatment of glioblastomas: special emphasis on cell migration and the resistance of migrating glioblastoma cells to apoptosis. J Clin Oncol. 23:2411–2422. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Lefranc F, Facchini V and Kiss R: Proautophagic drugs: a novel means to combat apoptosis-resistant cancers, with a special emphasis on glioblastomas. Oncologist. 12:1395–1403. 2007. View Article : Google Scholar

29 

Chan JA, Krichevsky AM and Kosik KS: MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 65:6029–6033. 2005. View Article : Google Scholar : PubMed/NCBI

30 

Nagane M, Levitzki A, Gazit A, Cavenee WK and Huang HJ: Drug resistance of human glioblastoma cells conferred by a tumor-specific mutant epidermal growth factor receptor through modulation of Bcl-XL and caspase-3-like proteases. Proc Natl Acad Sci USA. 95:5724–5729. 1998. View Article : Google Scholar : PubMed/NCBI

31 

Savill J, Dransfield I, Gregory C and Haslett C: A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol. 2:965–975. 2002. View Article : Google Scholar : PubMed/NCBI

32 

Hartwell LH and Kastan MB: Cell cycle control and cancer. Science. 266:1821–1828. 1994. View Article : Google Scholar : PubMed/NCBI

33 

Bedi A, Pasricha PJ, Akhtar AJ, et al: Inhibition of apoptosis during development of colorectal cancer. Cancer Res. 55:1811–1816. 1995.PubMed/NCBI

34 

Hanahan D and Weinberg RA: The hallmarks of cancer. Cell. 100:57–70. 2000. View Article : Google Scholar : PubMed/NCBI

35 

Ye J and Koumenis C: ATF4, an ER stress and hypoxia-inducible transcription factor and its potential role in hypoxia tolerance and tumorigenesis. Curr Mol Med. 9:411–416. 2009. View Article : Google Scholar : PubMed/NCBI

36 

Koumenis C: ER stress, hypoxia tolerance and tumor progression. Curr Mol Med. 6:55–69. 2006. View Article : Google Scholar : PubMed/NCBI

37 

Hitomi J, Katayama T, Eguchi Y, et al: Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and Abeta-induced cell death. J Cell Biol. 165:347–356. 2004. View Article : Google Scholar : PubMed/NCBI

38 

Shen S, Zhang Y, Wang Z, Liu R and Gong X: Bufalin induces the interplay between apoptosis and autophagy in glioma cells through endoplasmic reticulum stress. Int J Biol Sci. 10:212–224. 2014. View Article : Google Scholar : PubMed/NCBI

39 

Ogata M, Hino S, Saito A, et al: Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol. 26:9220–9231. 2006. View Article : Google Scholar : PubMed/NCBI

40 

Høyer-Hansen M and Jäättelä M: Connecting endoplasmic reticulum stress to autophagy by unfolded protein response and calcium. Cell Death Differ. 14:1576–1582. 2007. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Pan JM, Zhou L, Wang GB, Xia GW, Xue K, Cui XG, Shi HZ, Liu JH and Hu J: Fatsioside A inhibits the growth of glioma cells via the induction of endoplasmic reticulum stress-mediated apoptosis. Mol Med Rep 11: 3493-3498, 2015.
APA
Pan, J., Zhou, L., Wang, G., Xia, G., Xue, K., Cui, X. ... Hu, J. (2015). Fatsioside A inhibits the growth of glioma cells via the induction of endoplasmic reticulum stress-mediated apoptosis. Molecular Medicine Reports, 11, 3493-3498. https://doi.org/10.3892/mmr.2015.3213
MLA
Pan, J., Zhou, L., Wang, G., Xia, G., Xue, K., Cui, X., Shi, H., Liu, J., Hu, J."Fatsioside A inhibits the growth of glioma cells via the induction of endoplasmic reticulum stress-mediated apoptosis". Molecular Medicine Reports 11.5 (2015): 3493-3498.
Chicago
Pan, J., Zhou, L., Wang, G., Xia, G., Xue, K., Cui, X., Shi, H., Liu, J., Hu, J."Fatsioside A inhibits the growth of glioma cells via the induction of endoplasmic reticulum stress-mediated apoptosis". Molecular Medicine Reports 11, no. 5 (2015): 3493-3498. https://doi.org/10.3892/mmr.2015.3213
Copy and paste a formatted citation
x
Spandidos Publications style
Pan JM, Zhou L, Wang GB, Xia GW, Xue K, Cui XG, Shi HZ, Liu JH and Hu J: Fatsioside A inhibits the growth of glioma cells via the induction of endoplasmic reticulum stress-mediated apoptosis. Mol Med Rep 11: 3493-3498, 2015.
APA
Pan, J., Zhou, L., Wang, G., Xia, G., Xue, K., Cui, X. ... Hu, J. (2015). Fatsioside A inhibits the growth of glioma cells via the induction of endoplasmic reticulum stress-mediated apoptosis. Molecular Medicine Reports, 11, 3493-3498. https://doi.org/10.3892/mmr.2015.3213
MLA
Pan, J., Zhou, L., Wang, G., Xia, G., Xue, K., Cui, X., Shi, H., Liu, J., Hu, J."Fatsioside A inhibits the growth of glioma cells via the induction of endoplasmic reticulum stress-mediated apoptosis". Molecular Medicine Reports 11.5 (2015): 3493-3498.
Chicago
Pan, J., Zhou, L., Wang, G., Xia, G., Xue, K., Cui, X., Shi, H., Liu, J., Hu, J."Fatsioside A inhibits the growth of glioma cells via the induction of endoplasmic reticulum stress-mediated apoptosis". Molecular Medicine Reports 11, no. 5 (2015): 3493-3498. https://doi.org/10.3892/mmr.2015.3213
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