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Article

The triterpenoid pristimerin induces U87 glioma cell apoptosis through reactive oxygen species-mediated mitochondrial dysfunction

  • Authors:
    • Yan-Yan Yan
    • Jian-Ping Bai
    • Yong Xie
    • Jie-Zhong Yu
    • Cun-Gen Ma
  • View Affiliations / Copyright

    Affiliations: Institute of Brain Science, Shanxi Datong University, Datong, Shanxi 037009, P.R. China
  • Pages: 242-248
    |
    Published online on: October 22, 2012
       https://doi.org/10.3892/ol.2012.982
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Abstract

It has become evident that some of the natural or synthetic triterpenoids are natural proteasome inhibitors that have great potential for use in cancer prevention and treatment. However, the mechanisms for the antitumor activity of triterpenoids remain to be elucidated. In the present study, we investigated the anticancer activities of a natural triterpenoid, pristimerin, and the signaling pathways affected. Pristimerin was found to possess potent cytotoxic effects, inducing apoptosis and inhibiting proliferation in U87 human glioma cells. Hoechst 33258 staining and Annexin V/PI double staining exhibited the typical nuclear features of apoptosis and increased the proportion of apoptotic Annexin V-positive cells in a dose-dependent manner, respectively. Moreover, western blotting assay revealed that this apoptotic induction was associated with activated caspase-9, caspase-3, PARP cleavage and downregulation of Bcl-xl/Bax in a concentration-dependent manner. Pristimerin also increased the generation of reactive oxygen species and induced the subsequent release of cytochrome c from the mitochondria into the cytosol. Additionally, pristimerin downregulated EGFR protein expression and inhibited downstream signaling pathways in U87 cells. Our results suggest that pristimerin may have potential as a new targeting therapeutic strategy in the treatment of EGFR-overexpressing gliomas.
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1 

Debatin KM: Activation of apoptosis pathways by anticancer drugs. Adv Exp Med Biol. 457:237–244. 1999. View Article : Google Scholar : PubMed/NCBI

2 

Hengartner MO: The biochemistry of apoptosis. Nature. 407:770–776. 2000. View Article : Google Scholar : PubMed/NCBI

3 

Kroemer G and Reed JC: Mitochondrial control of cell death. Nat Med. 6:513–519. 2000. View Article : Google Scholar

4 

Gulbins E, Dreschers S and Bock J: Role of mitochondria in apoptosis. Exp Physiol. 88:85–90. 2003. View Article : Google Scholar

5 

Friesen C, Fulda S and Debatin KM: Cytotoxic drugs and the CD95 pathway. Leukemia. 13:1854–1858. 1999. View Article : Google Scholar : PubMed/NCBI

6 

Sharma K, Wang RX, Zhang LY, et al: Death the Fas way: regulation and pathophysiology of CD95 and its ligand. Pharmacol Ther. 88:333–347. 2000. View Article : Google Scholar : PubMed/NCBI

7 

Gao JM, Wu WJ, Zhang JW and Konishi Y: The dihydro-beta-agarofuran sesquiterpenoids. Nat Prod Rep. 24:1153–1189. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Brinker AM, Ma J, Lipsky PE and Raskin I: Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae). Phytochemistry. 68:732–766. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Salminen A, Lehtonen M, Suuronen T, Kaarniranta K and Huuskonen J: Terpenoids: natural inhibitors of NF-kappaB signaling with anti-inflammatory and anticancer potential. Cell Mol Life Sci. 65:2979–2999. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Wu CC, Chan ML, Chen WY, Tsai CY, Chang FR and Wu YC: Pristimerin induces caspase-dependent apoptosis in MDA-MB-231 cells via direct effects on mitochondria. Mol Cancer Ther. 4:1277–1285. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Nagase M, Oto J, Sugiyama S, Yube K, Takaishi Y and Sakato N: Apoptosis induction in HL-60 cells and inhibition of topoisomerase II by triterpene celastrol. Biosci Biotechnol Biochem. 67:1883–1887. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Yang H, Landis-Piwowar KR, Lu D, et al: Pristimerin induces apoptosis by targeting the proteasome in prostate cancer cells. J Cell Biochem. 103:234–244. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Lu Z, Jin Y, Chen C, Li J, Cao Q and Pan J: Pristimerin induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation by blocking NF-kappaB signaling and depleting Bcr-Abl. Mol Cancer. 9:1122010. View Article : Google Scholar

14 

Tiedemann RE, Schmidt J, Keats JJ, et al: Identification of a potent natural triterpenoid inhibitor of proteosome chymotrypsin-like activity and NF-kappaB with antimyeloma activity in vitro and in vivo. Blood. 113:4027–4037. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Shao CJ, Fu J, Shi HL, Mu YG and Chen ZP: Activities of DNA-PK and Ku86, but not Ku70, may predict sensitivity to cisplatin in human gliomas. J Neurooncol. 89:27–35. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Fu J, Shao CJ, Chen FR, Ng HK and Chen ZP: Autophagy induced by valproic acid is associated with oxidative stress in glioma cell lines. Neuro Oncology. 12:328–340. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Yan YY, Zheng LS, Zhang X, et al: Blockade of Her2/neu binding to Hsp90 by emodin azide methyl anthraquinone derivative induces proteasomal degradation of Her2/neu. Mol Pharm. 8:1687–1697. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Yan Y, Su X, Liang Y, et al: Emodin azide methyl anthraquinone derivative triggers mitochondrial-dependent cell apoptosis involving in caspase-8-mediated Bid cleavage. Mol Cancer Ther. 7:1688–1697. 2008. View Article : Google Scholar

19 

Zhang JY, Wu HY, Xia XK, et al: Anthracenedione derivative 1403P-3 induces apoptosis in KB and KBv200 cells via reactive oxygen species-independent mitochondrial pathway and death receptor pathway. Cancer Biol Ther. 6:1413–1421. 2007. View Article : Google Scholar

20 

Nakagawa T, Zhu H, Morishima N, et al: Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature. 403:98–103. 2000. View Article : Google Scholar : PubMed/NCBI

21 

Barry M, Heibein JA, Pinkoski MJ, et al: Granzyme B short-circuits the need for caspase 8 activity during granule-mediated cytotoxic T-lymphocyte killing by directly cleaving Bid. Mol Cell Biol. 20:3781–3794. 2000. View Article : Google Scholar : PubMed/NCBI

22 

Lavrik IN, Golks A, Baumann S and Krammer PH: Caspase-2 is activated at the CD95 death-inducing signaling complex in the course of CD95-induced apoptosis. Blood. 108:559–565. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Vanhaesebroeck B and Alessi DR: The PI3K-PDK1 connection: more than just a road to PKB. Biochem J 346 Pt. 3:561–576. 2000. View Article : Google Scholar : PubMed/NCBI

24 

Marte BM and Downward J: PKB/Akt: connecting phosphoinositide 3-kinase to cell survival and beyond. Trends Biochem Sci. 22:355–358. 1997. View Article : Google Scholar : PubMed/NCBI

25 

Surawicz TS, Davis F, Freels S, Laws ER Jr and Menck HR: Brain tumor survival: results from the National Cancer Data Base. J Neurooncol. 40:151–160. 1998. View Article : Google Scholar : PubMed/NCBI

26 

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 : PubMed/NCBI

27 

Shirota O, Morita H, Takeya K and Itokawa H: Cytotoxic aromatic triterpenes from Maytenus ilicifolia and Maytenus chuchuhuasca. J Nat Prod. 57:1675–1681. 1994. View Article : Google Scholar : PubMed/NCBI

28 

Chang FR, Hayashi K, Chen IH, et al: Antitumor agents. 228 five new agarofurans, Reissantins A–E, and cytotoxic principles from Reissantia buchananii. J Nat Prod. 66:1416–1420. 2003.PubMed/NCBI

29 

Li SS, Tang QL, Wang SH, Chen YH, Liu JJ and Yang XM: Simultaneously targeting Bcl-2 and Akt pathways reverses resistance of nasopharyngeal carcinoma to TRAIL synergistically. Tumori. 97:762–770. 2011.PubMed/NCBI

30 

Yoo NJ, Kim MS, Park SW, et al: Expression analysis of caspase-6, caspase-9 and BNIP3 in prostate cancer. Tumori. 96:138–142. 2010.PubMed/NCBI

31 

Fleury C, Mignotte B and Vayssiere JL: Mitochondrial reactive oxygen species in cell death signaling. Biochimie. 84:131–141. 2002. View Article : Google Scholar : PubMed/NCBI

32 

Xia Z, Lundgren B, Bergstrand A, DePierre JW and Nassberger L: Changes in the generation of reactive oxygen species and in mitochondrial membrane potential during apoptosis induced by the antidepressants imipramine, clomipramine, and citalopram and the effects on these changes by Bcl-2 and Bcl-X(L). Biochem Pharmacol. 57:1199–1208. 1999. View Article : Google Scholar

33 

Chan WH, Wu CC and Yu JS: Curcumin inhibits UV irradiation-induced oxidative stress and apoptotic biochemical changes in human epidermoid carcinoma A431 cells. J Cell Biochem. 90:327–338. 2003. View Article : Google Scholar : PubMed/NCBI

34 

Byun JY, Kim MJ, Eum DY, et al: Reactive oxygen species-dependent activation of Bax and poly(ADP-ribose) polymerase-1 is required for mitochondrial cell death induced by triterpenoid pristimerin in human cervical cancer cells. Mol Pharmacol. 76:734–744. 2009. View Article : Google Scholar

35 

Mani A and Gelmann EP: The ubiquitin-proteasome pathway and its role in cancer. J Clin Oncol. 23:4776–4789. 2005. View Article : Google Scholar : PubMed/NCBI

36 

Ciechanover A: The ubiquitin-proteasome pathway: on protein death and cell life. EMBO J. 17:7151–7160. 1998. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yan Y, Bai J, Xie Y, Yu J and Ma C: The triterpenoid pristimerin induces U87 glioma cell apoptosis through reactive oxygen species-mediated mitochondrial dysfunction . Oncol Lett 5: 242-248, 2013.
APA
Yan, Y., Bai, J., Xie, Y., Yu, J., & Ma, C. (2013). The triterpenoid pristimerin induces U87 glioma cell apoptosis through reactive oxygen species-mediated mitochondrial dysfunction . Oncology Letters, 5, 242-248. https://doi.org/10.3892/ol.2012.982
MLA
Yan, Y., Bai, J., Xie, Y., Yu, J., Ma, C."The triterpenoid pristimerin induces U87 glioma cell apoptosis through reactive oxygen species-mediated mitochondrial dysfunction ". Oncology Letters 5.1 (2013): 242-248.
Chicago
Yan, Y., Bai, J., Xie, Y., Yu, J., Ma, C."The triterpenoid pristimerin induces U87 glioma cell apoptosis through reactive oxygen species-mediated mitochondrial dysfunction ". Oncology Letters 5, no. 1 (2013): 242-248. https://doi.org/10.3892/ol.2012.982
Copy and paste a formatted citation
x
Spandidos Publications style
Yan Y, Bai J, Xie Y, Yu J and Ma C: The triterpenoid pristimerin induces U87 glioma cell apoptosis through reactive oxygen species-mediated mitochondrial dysfunction . Oncol Lett 5: 242-248, 2013.
APA
Yan, Y., Bai, J., Xie, Y., Yu, J., & Ma, C. (2013). The triterpenoid pristimerin induces U87 glioma cell apoptosis through reactive oxygen species-mediated mitochondrial dysfunction . Oncology Letters, 5, 242-248. https://doi.org/10.3892/ol.2012.982
MLA
Yan, Y., Bai, J., Xie, Y., Yu, J., Ma, C."The triterpenoid pristimerin induces U87 glioma cell apoptosis through reactive oxygen species-mediated mitochondrial dysfunction ". Oncology Letters 5.1 (2013): 242-248.
Chicago
Yan, Y., Bai, J., Xie, Y., Yu, J., Ma, C."The triterpenoid pristimerin induces U87 glioma cell apoptosis through reactive oxygen species-mediated mitochondrial dysfunction ". Oncology Letters 5, no. 1 (2013): 242-248. https://doi.org/10.3892/ol.2012.982
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