Int J Stomatol

Int J Stomatol ›› 2020, Vol. 47 ›› Issue (4): 406-412.doi: 10.7518/gjkq.2020079

• Original Articles • Previous Articles     Next Articles

Inhibitory effect of pyrroloquinoline quinone on epithelial-mesenchymal transition in tongue squamous cell carcinoma cells

Wu Nan1,Li Bin2()   

  1. 1. School of Medicine, Yongzhou Vocational Technical College, Yongzhou 425000, China
    2. School of Stomatology, Hunan University of Medicine, Huaihua 418000, China
  • Received:2019-12-28 Revised:2020-04-27 Online:2020-07-01 Published:2020-07-10
  • Contact: Bin Li E-mail:2996967631@qq.com
  • Supported by:
    This study was supported by Research Project of Hunan Provincial Department of Education(18C1132);Youth Program of Hunan Natural Science Foundation(2019JJ50423)

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Abstract:

Objective To study the effect of pyrroloquinoline quinone (PQQ) on epithelial-mesenchymal transition (EMT) and its underlying mechanisms in human tongue squamous cell carcinoma cells. Methods Human tongue squamous cell carcinoma cell line CAL27 was selected. MTT assay was used to determine the effect of PQQ on cell viability. The invasion and migration abilities of CAL27 cells were checked by Transwell assay and wound healing test. Fluorescence microscopy was performed to measure the effect of PQQ on the generation of reactive oxygen species (ROS) in CAL27 cells. The expression levels of EMT-related proteins (E-cadherin, Vimentin, and zinc-finger transcription factor Snail) and nuclear factor-κB (NF-κB) activator protein in CAL27 cells under the treatment of PQQ, N-acetyl-L-cysteine (NAC), and phorbol-12-myristate-13-acetate (PMA) were determined by Western blot. Results PQQ inhibited the proliferation of CAL27 cells in a dose-dependent manner, and the half maximal inhibitory concentration of PQQ after 24 h was 6.69 μmol·L -1. Transwell assay and wound healing test showed that 2 μmol·L -1 PQQ inhibited the invasion and migration abilities of CAL27 cells (P<0.05). Cellular ROS level was signi-ficantly boosted (P<0.001) after treatment with 2 μmol·L -1 PQQ for 24 h. PQQ (2 μmol·L -1) increased the expression level of E-cadherin and inhibited the expression levels of Vimentin, Snail, and NF-κB (P<0.001). The coincubation of PQQ with NAC or PMA yielded the following experimental results: 1) NAC could reduce the regulatory effect of PQQ on EMT-related proteins and NF-κB activator protein (P<0.01) such that the increased expression level of E-cadherin was inhibited and the inhibited expression levels of Vimentin, Snail, and NF-κB were increased; 2) PMA could also reduce the regulatory effect of PQQ on EMT-related proteins (P<0.05). Conclusion PQQ can inhibit the EMT process in tongue squamous cell carcinoma cells, and ROS and the NF-κB signaling pathway may play an important role in this process.

Key words: human tongue squamous cell carcinoma, pyrroloquinoline quinone, epithelial-mesenchymal transition, reactive oxygen species, nuclear factor-κB

CLC Number: 

  • R730.5

TrendMD: 

Fig 1

Effect of PQQ on CAL27 cell proliferation"

Fig 2

The results of Transwell assay inverted phase contrast microscope × 200"

Fig 3

Effect of PQQ at different concentrations on invasiveness of CAL27 cells"

Fig 4

Effect of PQQ at different concentrations on migration of CAL-27 cells"

Fig 5

The results of wound healing test inverted phase contrast microscope × 40"

Fig 6

Production of intracellular ROS induced by PQQ at different concentrations electron fluorescence microscope × 200"

Fig 7

Under the treatment of PQQ and NAC, Western blot results of EMT-related proteins and NF-κB expression in CAL27 cells"

Fig 8

Under the treatment of PQQ and NAC, statistical results of EMT-related proteins and NF-κB expression in CAL27 cells"

Fig 9

Under the treatment of PQQ and PMA, Western blot results of EMT-related proteins expression in CAL27 cells"

Fig 10

Under the treatment of PQQ and PMA, statistical results of EMT-related proteins expression in CAL27 cells"

[1] Siegel R, Ma JM, Zou ZH, et al. Cancer statistics, 2014[J]. CA: Cancer J Clin, 2014,64(1):9-29.
[2] Tanaka F, Yoshimoto S, Okamura K, et al. Nuclear PKM2 promotes the progression of oral squamous cell carcinoma by inducing EMT and post-transla-tionally repressing TGIF2[J]. Oncotarget, 2018,9(73):33745-33761.
doi: 10.18632/oncotarget.25850 pmid: 30333907
[3] Akagawa M, Nakano M, Ikemoto K. Recent progress in studies on the health benefits of pyrroloquinoline quinone[J]. Biosci Biotechnol Biochem, 2016,80(1):13-22.
doi: 10.1080/09168451.2015.1062715 pmid: 26168402
[4] Zhang J, Meruvu S, Bedi YS, et al. Pyrroloquinoline quinone increases the expression and activity of Sirt1 and -3 genes in HepG2 cells[J]. Nutr Res, 2015,35(9):844-849.
doi: 10.1016/j.nutres.2015.06.014 pmid: 26275361
[5] Wen LC, Lu XY, Wang R, et al. Pyrroloquinoline quinone induces chondrosarcoma cell apoptosis by increasing intracellular reactive oxygen species[J]. Mol Med Rep, 2018,17(5):7184-7190.
doi: 10.3892/mmr.2018.8745 pmid: 29568949
[6] Xiong XH, Zhao Y, Ge X, et al. Production and ra-dioprotective effects of pyrroloquinoline quinone[J]. Int J Mol Sci, 2011,12(12):8913-8923.
doi: 10.3390/ijms12128913 pmid: 22272111
[7] Min ZH, Wang LY, Jin JJ, et al. Pyrroloquinoline quinone induces cancer cell apoptosis via mitochon-drial-dependent pathway and down-regulating cel-lular bcl-2 protein expression[J]. J Cancer, 2014,5(7):609-624.
doi: 10.7150/jca.9002 pmid: 25161699
[8] Sato K, Toriyama M. Effect of pyrroloquinoline quinone (PQQ) on melanogenic protein expression in murine B16 melanoma[J]. J Dermatol Sci, 2009,53(2):140-145.
doi: 10.1016/j.jdermsci.2008.08.017 pmid: 19013771
[9] 陈冠辉, 侯劲松. 低氧和自噬与肿瘤的发生发展[J]. 国际口腔医学杂志, 2016,43(5):584-588.
Chen GH, Hou JS. Hypoxia and autophagy and their correlation with tumorigenesis and development[J]. Int J Stomatol, 2016,43(5):584-588.
[10] Sreevalsan S, Safe S. Reactive oxygen species and colorectal cancer[J]. Curr Colorectal Cancer Rep, 2013,9(4):350-357.
doi: 10.1007/s11888-013-0190-5 pmid: 25584043
[11] Chaiswing L, St Clair WH, St Clair DK. Redox para-dox: a novel approach to therapeutics-resistant cancer[J]. Antioxid Redox Signal, 2018, 29(13): 1237-1272.
doi: 10.1089/ars.2017.7485 pmid: 29325444
[12] Sokolova O, Naumann M. NF-κB signaling in gas-tric cancer[J]. Toxins (Basel), 2017,9(4):E119.
[13] Nomura A, Majumder K, Giri B, et al. Inhibition of NF-kappa B pathway leads to deregulation of epithe-lial-mesenchymal transition and neural invasion in pancreatic cancer[J]. Lab Invest, 2016,96(12):1268-1278.
doi: 10.1038/labinvest.2016.109 pmid: 27775688
[14] Tong LY, Yuan Y, Wu SY. Therapeutic microRNAs targeting the NF-kappa B signaling circuits of cancers[J]. Adv Drug Deliv Rev, 2015,81:1-15.
doi: 10.1016/j.addr.2014.09.004 pmid: 25220353
[15] Wu HC, Jiang KF, Yin NN, et al. Thymol mitigates lipopolysaccharide-induced endometritis by regula-ting the TLR4- and ROS-mediated NF-κB signaling pathways[J]. Oncotarget, 2017,8(12):20042-20055.
doi: 10.18632/oncotarget.15373 pmid: 28223539
[16] Shanmugam R, Kusumanchi P, Cheng L, et al. A water-soluble parthenolide analogue suppresses in vivo prostate cancer growth by targeting NFkappaB and generating reactive oxygen species[J]. Prostate, 2010,70(10):1074-1086.
doi: 10.1002/pros.21141 pmid: 20209491
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