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All‑trans retinoic acid enhances temozolomide‑induced autophagy in human glioma cells U251 via targeting Keap1/Nrf2/ARE signaling pathway

  • Authors:
    • Lin Shi
    • Hongyuan Li
    • Yang Zhan
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, Dezhou People's Hospital, Dezhou, Shandong 253014, P.R. China, Department of Pathology, Dezhou People's Hospital, Dezhou, Shandong 253014, P.R. China
    Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2709-2714
    |
    Published online on: June 27, 2017
       https://doi.org/10.3892/ol.2017.6482
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Abstract

The present study evaluated the retinoic acid (RA) enhancement of temozolomide (TMZ) effects on the human glioma cells U251 and explored its underlying molecular mechanism. The cell growth was detected using the MTT assay and the cell cycle was assessed by flow cytometry. Cell apoptosis was analyzed by Annexin V/propidium iodide staining, and the cell morphology was evaluated using transmission electron microscopy (TEM). Additionally, reverse transcription‑PCR and western blot analysis were applied to detect the mRNA and protein levels. The RA treatment in combination with TMZ in the human U251 cells further inhibited cells growth, arresting cell cycle progression at the G0/G1 phase, and significantly induced apoptosis of U251 cells. After the RA+TMZ treatment of U251 cells, autophagy associated proteins Beclin 1 and LC3B were significantly increased, and the TEM analysis were consistent with autophagy protein levels. Moreover, Keap1/Nrf2/ARE expression was downregulated significantly, indicating the involvement in the mechanisms that RA treatment could enhance the TMZ effects on U251 cells. RA treatment in combination with TMZ may provide some experimental evidence for the possible effect of RA+TMZ against the growth and the proliferation of glioma cells. Therefore, the RA+TMZ administration may have potential utility for glioblastoma treatment.
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1 

Hathout L, Ellingson BM, Cloughesy T and Pope WB: A novel bicompartmental mathematical model of glioblastoma multiforme. Int J Oncol. 46:825–832. 2015.PubMed/NCBI

2 

Huse JT and Holland EC: Targeting brain cancer: Advances in the molecular pathology of malignant glioma and medulloblastoma. Nat Rev Cancer. 10:319–331. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Bryukhovetskiy IS, Dyuizen IV, Shevchenko VE, Bryukhovetski AS, Mischenko PV, Milkina EV and Khotimchenko YS: Hematopoietic stem cells as a tool for the treatment of glioblastoma multiforme. Mol Med Rep. 14:4511–4520. 2016.PubMed/NCBI

4 

Knisely JP and Baehring JM: A silver lining on the horizon for glioblastoma. Lancet Oncol. 10:434–435. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Nanegrungsunk D, Onchan W, Chattipakorn N and Chattipakorn SC: Current evidence of temozolomide and bevacizumab in treatment of gliomas. Neurol Res. 37:167–183. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Messaoudi K, Clavreul A and Lagarce F: Toward an effective strategy in glioblastoma treatment. Part II: RNA interference as a promising way to sensitize glioblastomas to temozolomide. Drug Discov Today. 20:772–779. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Wait SD, Prabhu RS, Burri SH, Atkins TG and Asher AL: Polymeric drug delivery for the treatment of glioblastoma. Neuro-oncol. 17 Suppl 2:ii9–ii23. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Fu YS, Wang Q, Ma JX, Yang XH, Wu ML, Zhang KL, Kong QY, Chen XY, Sun Y, Chen NN, et al: CRABP-II methylation: A critical determinant of retinoic acid resistance of medulloblastoma cells. Mol Oncol. 6:48–61. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Sakoe Y, Sakoe K, Kirito K, Ozawa K and Komatsu N: FOXO3A as a key molecule for all-trans retinoic acid-induced granulocytic differentiation and apoptosis in acute promyelocytic leukemia. Blood. 115:3787–3795. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Manor D, Shmidt EN, Budhu A, Flesken-Nikitin A, Zgola M, Page R, Nikitin AY and Noy N: Mammary carcinoma suppression by cellular retinoic acid binding protein-II. Cancer Res. 63:4426–4433. 2003.PubMed/NCBI

11 

Niederreither K, Abu-Abed S, Schuhbaur B, Petkovich M, Chambon P and Dollé P: Genetic evidence that oxidative deriva tives of retinoic acid are not involved in retinoid signaling during mouse development. Nat Genet. 31:84–88. 2002.PubMed/NCBI

12 

Jacobs S, Lie DC, DeCicco KL, Shi Y, DeLuca LM, Gage FH and Evans RM: Retinoic acid is required early during adult neurogenesis in the dentate gyrus. Proc Natl Acad Sci USA. 103:pp. 3902–3907. 2006; View Article : Google Scholar : PubMed/NCBI

13 

Sui X, Chen R, Wang Z, Huang Z, Kong N, Zhang M, Han W, Lou F, Yang J, Zhang Q, et al: Autophagy and chemotherapy resistance: A promising therapeutic target for cancer treatment. Cell Death Dis. 4:e8382013. View Article : Google Scholar : PubMed/NCBI

14 

Paglin S, Hollister T, Delohery T, Hackett N, McMahill M, Sphicas E, Domingo D and Yahalom J: A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. Cancer Res. 61:439–444. 2001.PubMed/NCBI

15 

Fulda S and Kögel D: Cell death by autophagy: Emerging molecular mechanisms and implications for cancer therapy. Oncogene. 34:5105–5113. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Galluzzi L, Morselli E, Vicencio JM, Kepp O, Joza N, Tajeddine N and Kroemer G: Life, death and burial: Multifaceted impact of autophagy. Biochem Soc Trans. 36:786–790. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Codogno P and Meijer AJ: Autophagy and signaling: Their role in cell survival and cell death. Cell Death Differ. 12 Suppl 2:1509–1518. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Zhang C, Jia X, Wang K, Bao J, Li P, Chen M, Wan JB, Su H, Mei Z and He C: Polyphyllin VII induces an autophagic cell death by activation of the JNK pathway and inhibition of PI3K/AKT/mTOR pathway in HepG2 cells. PLoS One. 11:e01474052016. View Article : Google Scholar : PubMed/NCBI

19 

Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y and Yoshimori T: LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 19:5720–5728. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Cao Y and Klionsky DJ: Physiological functions of Atg6/Beclin 1: A unique autophagy-related protein. Cell Res. 17:839–849. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Yan Y, Xu Z, Dai S, Qian L, Sun L and Gong Z: Targeting autophagy to sensitive glioma to temozolomide treatment. J Exp Clin Cancer Res. 35:232016. View Article : Google Scholar : PubMed/NCBI

22 

Zhang C, Zhu Q, He H, Jiang L, Qiang Q, Hu L, Hu G, Jiang Y, Ding X and Lu Y: RIZ1: A potential tumor suppressor in glioma. BMC Cancer. 15:9902015. View Article : Google Scholar : PubMed/NCBI

23 

Zhang C, Cai Z, Liang Q, Wang Q, Lu Y, Hu L and Hu G: RLIP76 depletion enhances autophagic flux in U251 cells. Cell Mol Neurobiol. 37:555–562. 2016. View Article : Google Scholar : PubMed/NCBI

24 

Kanzawa T, Germano IM, Komata T, Ito H, Kondo Y and Kondo S: Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. Cell Death Differ. 11:448–457. 2004. View Article : Google Scholar : PubMed/NCBI

25 

Shinojima N, Yokoyama T, Kondo Y and Kondo S: Roles of the Akt/mTOR/p70S6K and ERK1/2 signaling pathways in curcumin-induced autophagy. Autophagy. 3:635–637. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Natsumeda M, Maitani K, Liu Y, Miyahara H, Kaur H, Chu Q, Zhang H, Kahlert UD and Eberhart CG: Targeting notch signaling and autophagy increases cytotoxicity in glioblastoma neurospheres. Brain Pathol. 26:713–723. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Chen Y, Meng D, Wang H, Sun R, Wang D, Wang S, Fan J, Zhao Y, Wang J, Yang S, et al: VAMP8 facilitates cellular proliferation and temozolomide resistance in human glioma cells. Neuro Oncol. 17:407–418. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Pratt J and Annabi B: Induction of autophagy biomarker BNIP3 requires a JAK2/STAT3 and MT1-MMP signaling interplay in Concanavalin-A-activated U87 glioblastoma cells. Cell Signal. 26:917–924. 2014. View Article : Google Scholar : PubMed/NCBI

29 

Bordin DL, Lima M, Lenz G, Saffi J, Meira LB, Mésange P, Soares DG, Larsen AK, Escargueil AE and Henriques JA: DNA alkylation damage and autophagy induction. Mutat Res. 753:91–99. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Wagner E, Luo T, Sakai Y, Parada LF and Dräger UC: Retinoic acid delineates the topography of neuronal plasticity in postnatal cerebral cortex. Eur J Neurosci. 24:329–340. 2006. View Article : Google Scholar : PubMed/NCBI

31 

Baharvand H, Mehrjardi NZ, Hatami M, Kiani S, Rao M and Haghighi MM: Neural differentiation from human embryonic stem cells in a defined adherent culture condition. Int J Dev Biol. 51:371–378. 2007. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Shi L, Li H and Zhan Y: All‑trans retinoic acid enhances temozolomide‑induced autophagy in human glioma cells U251 via targeting Keap1/Nrf2/ARE signaling pathway. Oncol Lett 14: 2709-2714, 2017.
APA
Shi, L., Li, H., & Zhan, Y. (2017). All‑trans retinoic acid enhances temozolomide‑induced autophagy in human glioma cells U251 via targeting Keap1/Nrf2/ARE signaling pathway. Oncology Letters, 14, 2709-2714. https://doi.org/10.3892/ol.2017.6482
MLA
Shi, L., Li, H., Zhan, Y."All‑trans retinoic acid enhances temozolomide‑induced autophagy in human glioma cells U251 via targeting Keap1/Nrf2/ARE signaling pathway". Oncology Letters 14.3 (2017): 2709-2714.
Chicago
Shi, L., Li, H., Zhan, Y."All‑trans retinoic acid enhances temozolomide‑induced autophagy in human glioma cells U251 via targeting Keap1/Nrf2/ARE signaling pathway". Oncology Letters 14, no. 3 (2017): 2709-2714. https://doi.org/10.3892/ol.2017.6482
Copy and paste a formatted citation
x
Spandidos Publications style
Shi L, Li H and Zhan Y: All‑trans retinoic acid enhances temozolomide‑induced autophagy in human glioma cells U251 via targeting Keap1/Nrf2/ARE signaling pathway. Oncol Lett 14: 2709-2714, 2017.
APA
Shi, L., Li, H., & Zhan, Y. (2017). All‑trans retinoic acid enhances temozolomide‑induced autophagy in human glioma cells U251 via targeting Keap1/Nrf2/ARE signaling pathway. Oncology Letters, 14, 2709-2714. https://doi.org/10.3892/ol.2017.6482
MLA
Shi, L., Li, H., Zhan, Y."All‑trans retinoic acid enhances temozolomide‑induced autophagy in human glioma cells U251 via targeting Keap1/Nrf2/ARE signaling pathway". Oncology Letters 14.3 (2017): 2709-2714.
Chicago
Shi, L., Li, H., Zhan, Y."All‑trans retinoic acid enhances temozolomide‑induced autophagy in human glioma cells U251 via targeting Keap1/Nrf2/ARE signaling pathway". Oncology Letters 14, no. 3 (2017): 2709-2714. https://doi.org/10.3892/ol.2017.6482
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