Resveratrol inhibits glioma cell growth via targeting oncogenic microRNAs and multiple signaling pathways

  • Authors:
    • Guangxiu Wang
    • Fang Dai
    • Kai Yu
    • Zhifan Jia
    • Anling Zhang
    • Qiang Huang
    • Chunsheng Kang
    • Hao Jiang
    • Peiyu Pu
  • View Affiliations

  • Published online on: February 2, 2015     https://doi.org/10.3892/ijo.2015.2863
  • Pages: 1739-1747
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Abstract

Resveratrol (Res), a natural polyphenolic compound, has anticancer activity in a variety of cancers. In the present study, the antitumor effect and underlying molecular mechanism of Res on rat C6 glioma growth was studied. The results demonstrated that Res inhibited glioma cell proliferation, arrested cell cycle in S phase and induced apoptosis in vitro. Res also suppressed intracranial C6 tumor growth in vivo and prolonged survival in a fraction of the rats bearing intracranial gliomas. Res significantltly downregulated the specific miRs, including miR‑21, miR‑30a-5p and miR‑19, which have been identified as oncomiRs in our previous studies, and altered the expression of their targeting and crucial genes for glioma formation and progression such as p53, PTEN, EGFR, STAT3, COX-2, NF-κB and PI3K/AKT/mTOR pathway. Therefore, the anti-glioma effect of Res, at least in part, is through the regulation of oncogenic miRNAs. The effect of Res on non-coding RNAs should be studied further. Res is a potential multi-targeting drug for the treatment of gliomas.

References

1 

Kevin P, Becker, Yu J, et al: Status quo - standard-of-care medical and radiation therapy for glioblastoma. Cancer J. 18:12–19. 2012. View Article : Google Scholar

2 

Yang P, Wang Y, Peng X, et al: Management and survival rates in patients with glioma in China (2004–2010): a retrospective study from a single-institution. J Neurooncol. 2:259–266. 2013. View Article : Google Scholar

3 

Aggarwal BB, Bhardwaj A, Aggarwal RS, et al: Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res. 24:2783–2840. 2004.PubMed/NCBI

4 

Cao Y, Wang F, Liu HY, et al: Resveratrol induces apoptosis and differentiation in acute promyelocytic leukemia (NB4) cells. J Asian Nat Prod Res. 7:633–641. 2005. View Article : Google Scholar : PubMed/NCBI

5 

De la Lastra CA and Villegas I: Resveratrol as an anti-inflammatory and anti-aging agent: mechanisms and clinical implications. Mol Nutr Food Res. 49:405–430. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Castello L and Tessitore L: Resveratrol inhibits cell cycle progression in U937 cells. Oncol Rep. 13:133–137. 2005.

7 

Gao X, Xu YX, Divine G, et al: Disparate in vitro and in vivo antileukemic effects of resveratrol, a natural polyphenolic compound found in grapes. J Nutr. 132:2076–2081. 2002.PubMed/NCBI

8 

Jang M, Cai L, Udeani GO, et al: Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 275:218–220. 1997. View Article : Google Scholar : PubMed/NCBI

9 

Gagliano N, Moscheni C, Torri C, et al: Effect of resveratrol on matrix metalloproteinase-2 (MMP-2) and Secreted Protein Acidic and Rich in Cysteine (SPARC) on human cultured glioblastoma cells. Biomed Pharmacother. 59:359–364. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Jiang H, Zhang L, Kuo J, et al: Resveratrol-induced apoptotic death in human U251 glioma cells. Mol Cancer Ther. 4:554–561. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Tseng SH, Lin SM, Chen JC, et al: Resveratrol suppresses the angiogenesis and tumor growth of gliomas in rats. Clin Cancer Res. 10:2190–2202. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Yang YP, Chang YL, Huang PI, et al: Resveratrol suppresses tumorigenicity and enhances radiosensitivity in primary glioblastoma tumor initiating cells by inhibiting the STAT3 axis. J Cell Physiol. 227:976–993. 2012. View Article : Google Scholar

13 

Zhang W, Wang YE, Zhang Y, et al: Global epigenetic regulation of microRNAs in multiple myeloma. PLoS One. 9:e1109732014. View Article : Google Scholar : PubMed/NCBI

14 

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

15 

Tuomarila M, Luostari K, Soini Y, et al: Overexpression of microRNA-200c predicts poor outcome in patients with PR-negative breast cancer. PLoS One. 9:e1095082014. View Article : Google Scholar : PubMed/NCBI

16 

Wang KY, Ma J, Zhang FX, et al: MicroRNA-378 inhibits cell growth and enhances l-OHP-induced apoptosis in human colorectal cancer. IUBMB Life. 66:645–654. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Chen Q, Yang L, Xiao Y, et al: Circulating microRNA-182 in plasma and its potential diagnostic and prognostic value for pancreatic cancer. Med Oncol. 31:2252014. View Article : Google Scholar : PubMed/NCBI

18 

Li Yiwei, Kong Dejuan, Wang Zhiwei, et al: Regulation of microRNAs by natural agents: an emerging field in chemoprevention and chemotherapy research. Pharm Res. 27:1027–1041. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Melkamu T, Zhang X, Tan J, et al: Alteration of microRNA expression in vinyl-carbamateinduced mouse lung tumors and modulation by the chemopreventive agent indole-3-carbinol. Carcinogenesis. 31:252–258. 2010. View Article : Google Scholar

20 

Li Y, VandenBoom TG, Kong D, et al: Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelial-to-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells. Cancer Res. 69:6704–6712. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Sun M, Estrov Z, Ji Y, et al: Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells. Mol Cancer Ther. 7:464–473. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Jia Z, Wang K, Wang G, et al: MiR-30a-5p antisense oligonucleotide suppresses glioma cell growth by targeting SEPT7. PLoS One. 8:e550082013. View Article : Google Scholar : PubMed/NCBI

23 

Jia Z, Wang K, Zhang A, et al: MiR-19a and miR-19b overexpression in gliomas. Pathol Oncol Res. 19:847–853. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Zhou X, Ren Y, Moore L, et al: Downregulation of miR-21 inhibits EGFR pathway and suppresses the growth of human glioblastoma cells independent of PTEN status. Lab Invest. 90:144–155. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Pu P, Liu X, Liu A, et al: Inhibitory effect of antisense epidermal growth factor receptor RNA on the proliferation of rat C6 glioma cells in vitro and in vivo. J Neurosurg. 92:132–139. 2000. View Article : Google Scholar : PubMed/NCBI

26 

Pu P, Kang C, Li J, et al: The effects of antisense AKT2 RNA on the inhibition of malignant glioma cell growth in vitro and in vivo. J Neurooncol. 76:1–11. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Bove K, Lincoln DW and Tsan MF: Effect of resveratrol on growth of 4T1 breast cancer cells in vitro and in vivo. Biochem Biophys Res Commun. 291:1001–1005. 2002. View Article : Google Scholar : PubMed/NCBI

28 

Kuwajerwala N, Cifuentes E, Gautam S, et al: Resveratrol induces prostate cancer cell entry into S phase and inhibits DNA synthesis. Cancer Res. 62:2488–2492. 2002.PubMed/NCBI

29 

Kim YA, Lim SY, Rhee SH, et al: Resveratrol inhibits inducible nitric oxide synthase and cyclooxygenase-2 expression in beta-amyloid-treated C6 glioma cells. Int J Mol Med. 17:1069–1075. 2006.PubMed/NCBI

30 

Tili E, Michaille JJ, Alder H, et al: Resveratrol modulates the levels of microRNAs targeting genes encoding tumor-suppressors and effectors of TGFβ signaling pathway in SW480 cells. Biochem Pharmacol. 80:2057–2065. 2010. View Article : Google Scholar : PubMed/NCBI

31 

Sheth S, Jajoo S, Kaur T, et al: Resveratrol reduces prostate cancer growth and metastasis by inhibiting the Akt/MicroRNA-21 pathway. PLoS One. 7:e516552012. View Article : Google Scholar : PubMed/NCBI

32 

Krichevsky AM and Gabriely G: miR-21: a small multi-faceted RNA. J Cell Mol Med. 13:39–53. 2009. View Article : Google Scholar : PubMed/NCBI

33 

Papagiannakopoulos T, Shapiro A and Kosik KS: MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res. 68:8164–8172. 2008. View Article : Google Scholar : PubMed/NCBI

34 

Zhu S, Wu H, Wu F, et al: MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res. 18:350–359. 2008. View Article : Google Scholar : PubMed/NCBI

35 

Wang F, Li T, Zhang B, et al: MicroRNA-19a/b regulates multidrug resistance in human gastric cancer cells by targeting PTEN. Biochem Biophys Res Commun. 434:688–694. 2013. View Article : Google Scholar : PubMed/NCBI

36 

Zawrocki A and Biernat W: Epidermal growth factor receptor in glioblastoma. Folia Neuropathol. 43:123–132. 2005.PubMed/NCBI

37 

Pu P, Kang C, Zhang Z, et al: Downregulation of PIK3CB by siRNA suppresses malignant glioma cell growth in vitro and in vivo. Technol Cancer Res Treat. 5:271–280. 2006. View Article : Google Scholar : PubMed/NCBI

38 

Gürsel DB, Connell-Albert YS, Tuskan RG, et al: Control of proliferation in astrocytoma cells by the receptor tyrosine kinase/PI3K/AKT signaling axis and the use of PI-103 and TCN as potential anti-astrocytoma therapies. Neuro Oncol. 13:610–621. 2011. View Article : Google Scholar : PubMed/NCBI

39 

Ruano Y, Mollejo M, Camacho FI, et al: Identification of survival-related genes of the phosphatidylinositol 3′-kinase signaling pathway in glioblastoma multiforme. Cancer. 112:1575–1584. 2008. View Article : Google Scholar : PubMed/NCBI

40 

Kang CS, Pu PY, Li YH, et al: An in vitro study on the suppressive effect of glioma cell growth induced by plasmid-based small interference RNA (siRNA) targeting human epidermal growth factor receptor. J Neurooncol. 74:267–273. 2005. View Article : Google Scholar : PubMed/NCBI

41 

Brantley EC and Benveniste EN: Signal transducer and activator of transcription-3: a molecular hub for signaling pathways in gliomas. Mol Cancer Res. 6:675–684. 2008. View Article : Google Scholar : PubMed/NCBI

42 

Germain D and Frank DA: Targeting the cytoplasmic and nuclear functions of signal transducers and activators of transcription 3 for cancer therapy. Clin Cancer Res. 13:5665–5669. 2007. View Article : Google Scholar : PubMed/NCBI

43 

Quoc Trung L, Espinoza JL, Takami A, et al: Resveratrol induces cell cycle arrest and apoptosis in malignant NK cells via JAK2/STAT3 pathway inhibition. PLoS One. 8:e551832013. View Article : Google Scholar : PubMed/NCBI

44 

Han L, Yue X, Zhou X, et al: MicroRNA-21 expression is regulated by β-catenin/STAT3 pathway and promotes glioma cell invasion by direct targeting RECK. CNS Neurosci Ther. 18:573–583. 2012. View Article : Google Scholar : PubMed/NCBI

45 

Sminia P, Stoter TR, van der Valk P, et al: Expression of cyclooxygenase-2 and epidermal growth factor receptor in primary and recurrent glioblastoma multiforme. J Cancer Res Clin Oncol. 131:653–661. 2005. View Article : Google Scholar : PubMed/NCBI

46 

Banerjee S, Bueso-Ramos C and Aggarwal BB: Suppression of 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in rats by resveratrol: role of nuclear factor-kappaB, cyclooxygenase-2, and matrix metalloprotease 9. Cancer Res. 62:4945–4954. 2002.PubMed/NCBI

47 

Ji Q, Liu X, Fu X, et al: Resveratrol inhibits invasion and metastasis of colorectal cancer cells via MALAT1 mediated Wnt/β-catenin signal pathway. PLoS One. 8:e787002013. View Article : Google Scholar

48 

Pu P, Zhang Z, Kang C, et al: Downregulation of Wnt2 and beta-catenin by siRNA suppresses malignant glioma cell growth. Cancer Gene Ther. 16:351–361. 2009. View Article : Google Scholar

49 

Filippi-Chiela EC, Thomé MP, Bueno e Silva MM, et al: Resveratrol abrogates the temozolomide-induced G2 arrest leading to mitotic catastrophe and reinforces the temozolomide-induced senescence in glioma cells. BMC Cancer. 22:1472013. View Article : Google Scholar

50 

Nakada M, Furuta T, Hayashi Y, et al: The strategy for enhancing temozolomide against malignant glioma. Front Oncol. 2:982012. View Article : Google Scholar : PubMed/NCBI

51 

Huang H, Lin H, Zhang X, et al: Resveratrol reverses temozolomide resistance by downregulation of MGMT in T98G glioblastoma cells by the NF-κB-dependent pathway. Oncol Rep. 27:2050–2056. 2012.PubMed/NCBI

52 

Yuan Y, Xue X, Guo RB, et al: Resveratrol enhances the antitumor effects of temozolomide in glioblastoma via ROS-dependent AMPK-TSC-mTOR signaling pathway. CNS Neurosci Ther. 18:536–546. 2012. View Article : Google Scholar : PubMed/NCBI

53 

Gagliano N, Aldini G, Colombo G, et al: The potential of resveratrol against human gliomas. Anticancer Drugs. 21:140–150. 2010. View Article : Google Scholar

54 

Iguchi K, Toyama T, Ito T, et al: Antiandrogenic activity of resveratrol analogs in prostate cancer LNCaP cells. J Androl. 33:1208–1215. 2012. View Article : Google Scholar : PubMed/NCBI

55 

Szekeres T, Saiko P and Fritzer-Szekeres M: Chemopreventive effects of resveratrol and resveratrol derivatives. Ann NY Acad Sci. 1215:89–95. 2011. View Article : Google Scholar : PubMed/NCBI

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April 2015
Volume 46 Issue 4

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Copy and paste a formatted citation
APA
Wang, G., Dai, F., Yu, K., Jia, Z., Zhang, A., Huang, Q. ... Pu, P. (2015). Resveratrol inhibits glioma cell growth via targeting oncogenic microRNAs and multiple signaling pathways. International Journal of Oncology, 46, 1739-1747. https://doi.org/10.3892/ijo.2015.2863
MLA
Wang, G., Dai, F., Yu, K., Jia, Z., Zhang, A., Huang, Q., Kang, C., Jiang, H., Pu, P."Resveratrol inhibits glioma cell growth via targeting oncogenic microRNAs and multiple signaling pathways". International Journal of Oncology 46.4 (2015): 1739-1747.
Chicago
Wang, G., Dai, F., Yu, K., Jia, Z., Zhang, A., Huang, Q., Kang, C., Jiang, H., Pu, P."Resveratrol inhibits glioma cell growth via targeting oncogenic microRNAs and multiple signaling pathways". International Journal of Oncology 46, no. 4 (2015): 1739-1747. https://doi.org/10.3892/ijo.2015.2863