Galangin increases ERK1/2 phosphorylation to decrease ADAM9 expression and prevents invasion in A172 glioma cells

Lei,Deqiang; Zhang,Fangcheng; Yao,Dongxiao; Xiong,Nanxiang; Jiang,Xiaobing; Zhao,Hongyang

doi:10.3892/mmr.2017.7920

Galangin increases ERK1/2 phosphorylation to decrease ADAM9 expression and prevents invasion in A172 glioma cells

Authors:
- Deqiang Lei
- Fangcheng Zhang
- Dongxiao Yao
- Nanxiang Xiong
- Xiaobing Jiang
- Hongyang Zhao
View Affiliations

Affiliations: Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Published online on: October 27, 2017 https://doi.org/10.3892/mmr.2017.7920
Pages: 667-673

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Galangin (3,5,7‑trihydroxyflavone), is a natural flavonoid present in plants. Galangin is reported to exhibit anti‑cancer properties against various cancer types. The aim of the present study was to display the effects of galangin on glioma and its mechanism of action in A172 human glioma cancer cells. The results clearly indicated that treatment of galangin inhibited A172 cell migration and invasion under non‑toxic doses. A human proteinase array assay was conducted to elucidate the potential effects of galangin, and the obtained results demonstrated that treatment of galangin inhibited ADAM9 protein expression and mRNA expression, that are known to contribute to cancer progression. Sustained extracellular signal‑regulated kinase (Erk)1/2 activation was also monitored, which contributed to ADAM9 protein expression and mRNA inhibition as investigated using western blotting analysis and reverse transcription‑quantitative polymerase chain reaction experiment. Erk1/2 inhibition by inhibitor or small interfering (si)Erk transfection markedly terminated galangin‑inhibited A172 migration and invasion via an Erk1/2 activation mechanism. Collective results suggested that galangin may act as an effective chemotherapeutic agent for glioma cancer depending on its ability to bring about ADAM9 and Erk1/2 activation.

View Figures

View References

1	Takahashi H and Teramoto A: Trial of targeting therapy against malignant glioma using monoclonal antibody. J Nippon Med Sch. 71:2–3. 2004. View Article : Google Scholar : PubMed/NCBI
2	Souhami R and Tobias J: Cancer and its management. 2nd edition. Oxford: Blackwell Sciences; 1995
3	Bleehen NM and Stenning SP: A medical research council trial of two radiotherapy doses in the treatment of grades 3 and 4 astrocytoma. Br J Cancer. 64:769–774. 1991. View Article : Google Scholar : PubMed/NCBI
4	Kitange GJ, Templeton KL and Jenkins RB: Recent advances in the molecular genetics of primary gliomas. Curr Opin Oncol. 15:197–203. 2003. View Article : Google Scholar : PubMed/NCBI
5	Ramos S: Cancer chemoprevention and chemotherapy: Dietary polyphenols and signalling pathways. Mol Nutr Food Res. 52:507–526. 2008. View Article : Google Scholar : PubMed/NCBI
6	Li BH and Tian WX: Presence of fatty acid synthase inhibitors in the rhizome of Alpinia officinarum hance. J Enzym Inhib Med Ch. 18:349–356. 2003. View Article : Google Scholar
7	Volpi N: Separation of flavonoids and phenolic acids from propolis by capillary zone electrophoresis. Electrophoresis. 25:1872–1878. 2004. View Article : Google Scholar : PubMed/NCBI
8	Sulaiman GM, Al Sammarrae KW, Ad'hiah AH, Zucchetti M, Frapolli R, Bello E, Erba E, D'Incalci M and Bagnati R: Chemical characterization of Iraqi propolis samples and assessing their antioxidant potentials. Food Chem Toxicol. 49:2415–2421. 2011. View Article : Google Scholar : PubMed/NCBI
9	Heo MY, Sohn SJ and Au WW: Anti-genotoxicity of galangin as a cancer chemopreventive agent candidate. Mutat Res. 488:135–150. 2001. View Article : Google Scholar : PubMed/NCBI
10	Cushnie TP and Lamb AJ: Assessment of the antibacterial activity of galangin against 4-quinolone resistant strains of Staphylococcus aureus. Phytomedicine. 13:187–191. 2006. View Article : Google Scholar : PubMed/NCBI
11	Gwak J, Oh J, Cho M, Bae SK, Song IS, Liu KH, Jeong Y, Kim DE, Chung YH and Oh S: Galangin suppresses the proliferation of β-catenin response transcription positive cancer cells by promoting adenomatous polyposis coli/Axin/glycogen synthase kinase-3β-independent β-catenin degradation. Mol Pharmacol. 79:1014–1022. 2011. View Article : Google Scholar : PubMed/NCBI
12	Ha TK, Kim ME, Yoon JH, Bae SJ, Yeom J and Lee JS: Galangin induces human colon cancer cell death via the mitochondrial dysfunction and caspase-dependent pathway. Exp Biol Med (Maywood). 238:1047–1054. 2013. View Article : Google Scholar : PubMed/NCBI
13	Murray TJ, Yang X and Sherr DH: Growth of a human mammary tumor cell line is blocked by galangin, a naturally occurring bioflavonoid, and is accompanied by down-regulation of cyclins D3, E, and A. Breast Cancer Res. 8:R172006. View Article : Google Scholar : PubMed/NCBI
14	Zhang HT, Luo H, Wu J, Lan LB, Fan DH, Zhu KD, Chen XY, Wen M and Liu HM: Galangin induces apoptosis of hepatocellular carcinoma cells via the mitochondrial pathway. World J Gastroenterol. 16:3377–3384. 2010. View Article : Google Scholar : PubMed/NCBI
15	Zhang W, Lan Y, Huang Q and Hua Z: Galangin induces B16F10 melanoma cell apoptosis via mitochondrial pathway and sustained activation of p38 MAPK. Cytotechnology. 65:447–455. 2013. View Article : Google Scholar : PubMed/NCBI
16	Huang H, Chen AY, Rojanasakul Y, Ye X, Rankin GO and Chen YC: Dietary compounds galangin and myricetin suppress ovarian cancer cell angiogenesis. J Funct Foods. 15:464–475. 2015. View Article : Google Scholar : PubMed/NCBI
17	Bestwick CS and Milne L: Influence of galangin on HL-60 cell proliferation and survival. Cancer Lett. 243:80–89. 2006. View Article : Google Scholar : PubMed/NCBI
18	Szliszka E, Czuba ZP, Bronikowska J, Mertas A, Paradysz A and Krol W: Ethanolic extract of propolis augments TRAIL-induced apoptotic death in prostate cancer cells. Evid Based Complement Alternat Med. 2011:5351722011. View Article : Google Scholar : PubMed/NCBI
19	Wen M, Wu J, Luo H and Zhang H: Galangin induces autophagy through upregulation of p53 in HepG2 cells. Pharmacology. 89:247–255. 2012. View Article : Google Scholar : PubMed/NCBI
20	Wang G, Li Z, Tian N, Han L, Fu Y, Guo Z and Tian Y: miR-148b-3p inhibits malignant biological behaviors of human glioma cells induced by high HOTAIR expression. Oncol Lett. 12:879–86. 2016.PubMed/NCBI
21	Kim YH, Shin EK, Kim DH, Lee HH, Park JH and Kim JK: Antiangiogenic effect of licochalcone A. Biochem Pharmacol. 80:1152–1159. 2010. View Article : Google Scholar : PubMed/NCBI
22	Green JA, Elkington PT, Pennington CJ, Roncaroli F, Dholakia S, Moores RC, Bullen A, Porter JC, Agranoff D, Edwards DR and Friedland JS: Mycobacterium tuberculosis upregulates microglial matrix metalloproteinase-1 and −3 expression and secretion via NF kappaB- and activator protein-1-dependent monocyte networks. J Immunol. 184:6492–6503. 2010. View Article : Google Scholar : PubMed/NCBI
23	Huh JE, Jung IT, Choi J, Baek YH, Lee JD, Park DS and Choi DY: The natural flavonoid galangin inhibits osteoclastic bone destruction and osteoclastogenesis by suppressing NF-κB in collagen-induced arthritis and bone marrow-derived macrophages. Eur J Pharmacol. 698:57–66. 2013. View Article : Google Scholar : PubMed/NCBI
24	Jung YC, Kim ME, Yoon JH, Park PR, Youn HY, Lee HW and Lee JS: Anti-inflammatory effects of galangin on lipopolysaccharide-activated macrophages via ERK and NF-κB pathway regulation. Immunopharmacol Immunotoxicol. 36:426–432. 2014. View Article : Google Scholar : PubMed/NCBI
25	Wang Y, Wu J, Lin B, Li X, Zhang H, Ding H, Chen X, Lan L and Luo H: Galangin suppresses HepG2 cell proliferation by activating the TGF-β receptor/Smad pathway. Toxicology. 326:9–17. 2014. View Article : Google Scholar : PubMed/NCBI
26	Jung CH, Jang SJ, Ahn J, Gwon SY, Jeon TI, Kim TW and Ha TY: Alpinia officinarum inhibits adipocyte differentiation and high-fat diet-induced obesity in mice through regulation of adipogenesis and lipogenesis. J Med Food. 15:959–967. 2012. View Article : Google Scholar : PubMed/NCBI
27	Lotito SB and Frei B: Dietary flavonoids attenuate tumor necrosis factor alpha-induced adhesion molecule expression in human aortic endothelial cells. Structure-function relationships and activity after first pass metabolism. J Biol Chem. 281:37102–371010. 2006. View Article : Google Scholar : PubMed/NCBI
28	Kim HH, Bae Y and Kim SH: Galangin attenuates mast cell-mediated allergic inflammation. Food Chem Toxicol. 57:209–216. 2013. View Article : Google Scholar : PubMed/NCBI
29	Choi JK and Kim SH: Inhibitory effect of galangin on atopic dermatitis-like skin lesions. Food Chem Toxicol. 68:135–141. 2014. View Article : Google Scholar : PubMed/NCBI
30	O'Leary KA, de Pascual-Teresa S, Needs PW, Bao YP, O'Brien NM and Williamson G: Effect of flavonoids and vitamin E on cyclooxygenase-2 (COX-2) transcription. Mutat Res. 551:245–254. 2004. View Article : Google Scholar : PubMed/NCBI
31	Zhang HT, Luo H, Wu J, Lan LB, Fan DH, Zhu KD, Chen XY, Wen M and Liu HM: Galangin induces apoptosis of hepatocellular carcinoma cells via the mitochondrial pathway. World J Gastroenterol. 16:3377–3384. 2010. View Article : Google Scholar : PubMed/NCBI
32	Su L, Chen X, Wu J, Lin B, Zhang H, Lan L and Luo H: Galangin inhibits proliferation of hepatocellular carcinoma cells by inducing endoplasmic reticulum stress. Food Chem Toxicol. 62:810–816. 2013. View Article : Google Scholar : PubMed/NCBI
33	Zhang H, Li N, Wu J, Su L, Chen X, Lin B and Luo H: Galangin inhibits proliferation of HepG2 cells by activating AMPK via increasing the AMP/TAN ratio in a LKB1-independent manner. Eur J Pharmacol. 718:235–244. 2013. View Article : Google Scholar : PubMed/NCBI
34	Pandey M, Mathew A and Nair MK: Global perspective of tobacco habits and lung cancer: A lesson for third world countries. Eur J Cancer Prev. 8:271–279. 1999. View Article : Google Scholar : PubMed/NCBI
35	Spira A and Ettinger DS: Multidisciplinary management of lung cancer. N Engl J Med. 350:379–392. 2004. View Article : Google Scholar : PubMed/NCBI
36	Sarkar FH and Li YW: Targeting multiple signal pathways by chemopreventive agents for cancer prevention and therapy. Acta Pharmacol Sin. 28:1305–1315. 2007. View Article : Google Scholar : PubMed/NCBI
37	Weng CJ and Yen GC: Chemopreventive effects of dietary phytochemicals against cancer invasion and metastasis: Phenolic acids, monophenol, polyphenol, and their derivatives. Cancer Treat Rev. 38:76–87. 2012. View Article : Google Scholar : PubMed/NCBI
38	Chetty C, Rao JS and Lakka SS: Matrix metalloproteinase pharmacogenomics in non-small cell lung carcinoma. Pharmacogenomics. 12:535–546. 2011. View Article : Google Scholar : PubMed/NCBI
39	López-Otín C, Palavalli LH and Samuels Y: Protective roles of matrix metalloproteinases: From mouse models to human cancer. Cell Cycle. 8:3657–3662. 2009. View Article : Google Scholar : PubMed/NCBI
40	Li M, Xiao T, Zhang Y, Feng L, Lin D, Liu Y, Mao Y, Guo S, Han N, Di X, et al: Prognostic significance of matrix metalloproteinase-1 levels in peripheral plasma and tumour tissues of lung cancer patients. Lung Cancer. 69:341–347. 2010. View Article : Google Scholar : PubMed/NCBI
41	Kim EK and Choi EJ: Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta. 1802:396–405. 2010. View Article : Google Scholar : PubMed/NCBI
42	Wagner EF and Nebreda AR: Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer. 9:537–549. 2009. View Article : Google Scholar : PubMed/NCBI
43	Hennessy BT, Smith DL, Ram PT, Lu Y and Mills GB: Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov. 4:988–1004. 2005. View Article : Google Scholar : PubMed/NCBI
44	Yoon SO, Shin S, Lee HJ, Chun HK and Chung AS: Isoginkgetin inhibits tumor cell invasion by regulating phosphatidylinositol 3-kinase/Akt-dependent matrix metalloproteinase-9 expression. Mol Cancer Ther. 5:2666–2675. 2006. View Article : Google Scholar : PubMed/NCBI
45	Veit C, Genze F, Menke A, Hoeffert S, Gress TM, Gierschik P and Giehl K: Activation of phosphatidylinositol 3-kinase and extracellular signal-regulated kinase is required for glial cell line-derived neurotrophic factor-induced migration and invasion of pancreatic carcinoma cells. Cancer Res. 64:5291–5300. 2004. View Article : Google Scholar : PubMed/NCBI
46	Günther W, Skaftnesmo KO, Arnold H and Terzis AJ: Molecular approaches to brain tumour invasion. Acta Neurochir (Wien). 145:1029–1036. 2003. View Article : Google Scholar : PubMed/NCBI