Isoalantolactone inhibits the migration and invasion of human breast cancer MDA-MB-231 cells via suppression of the p38 MAPK/NF-κB signaling pathway

Wang,Jing; Cui,Li; Feng,Liang; Zhang,Zhenhai; Song,Jie; Liu,Dan; Jia,Xiaobin

doi:10.3892/or.2016.4954

Isoalantolactone inhibits the migration and invasion of human breast cancer MDA-MB-231 cells via suppression of the p38 MAPK/NF-κB signaling pathway

Authors:
- Jing Wang
- Li Cui
- Liang Feng
- Zhenhai Zhang
- Jie Song
- Dan Liu
- Xiaobin Jia
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Affiliations: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China
Published online on: July 20, 2016 https://doi.org/10.3892/or.2016.4954
Pages: 1269-1276

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Abstract

Isoalantolactone is a bioactive sesquiterpene lactone isolated from the flowering plant Inula helenium L. This study was conducted to assess the anti-migratory and anti-invasive activities of isoalantolactone in MDA-MB-231 cells, and to explore the underlying mechanisms. Wound-healing and Transwell chambers assays demonstrated that isoalantolactone inhibited the adhesion, migration and invasion of MDA-MB-231 cells. The activity and expression of MMP-2 and MMP-9 were downregulated by isoalantolactone in a dose-dependent manner. Additionally, isoalantolactone markedly decreased the p-p38 MAPK level, whereas no significant change in p-ERK1/2 and p-JNK1/2 was noted. The downregulation of MMP-2 and MMP-9 protein expression and suppression of in vitro invasion might be associated with the blockade of p38 MAPK activation. Furthermore, isoalantolactone blocked the translocation of NF-κB p65 from the cytoplasm into the nucleus. These results revealed that isoalantolactone inhibited the adhesion, migration and invasion of MDA-MB-231 cells via suppression of the p38 MAPK/NF-κB signaling pathway, and isoalantolactone might be an alternative treatment for breast cancer.

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1	Carvalho I, Milanezi F, Martins A, Reis RM and Schmitt F: Overexpression of platelet-derived growth factor receptor alpha in breast cancer is associated with tumour progression. Breast Cancer Res. 7:R788–R795. 2005. View Article : Google Scholar : PubMed/NCBI
2	Côme C, Laine A, Chanrion M, Edgren H, Mattila E, Liu X, Jonkers J, Ivaska J, Isola J, Darbon JM, et al: CIP2A is associated with human breast cancer aggressivity. Clin Cancer Res. 15:5092–5100. 2009. View Article : Google Scholar : PubMed/NCBI
3	Cheng X, Gu J, Zhang M, Yuan J, Zhao B, Jiang J and Jia X: Astragaloside IV inhibits migration and invasion in human lung cancer A549 cells via regulating PKC-α-ERK1/2-NF-κB pathway. Int Immunopharmacol. 23:304–313. 2014. View Article : Google Scholar : PubMed/NCBI
4	Mohammad MA, Zeeneldin AA, Abd Elmageed ZY, Khalil EH, Mahdy SM, Sharada HM, Sharawy SK and Abdel-Wahab AH: Clinical relevance of cyclooxygenase-2 and matrix metalloproteinases (MMP-2 and MT1-MMP) in human breast cancer tissue. Mol Cell Biochem. 366:269–275. 2012. View Article : Google Scholar : PubMed/NCBI
5	Kim TD, Song KS, Li G, Choi H, Park HD, Lim K, Hwang BD and Yoon WH: Activity and expression of urokinase-type plasminogen activator and matrix metalloproteinases in human colorectal cancer. BMC Cancer. 6:2112006. View Article : Google Scholar : PubMed/NCBI
6	Bodey B, Bodey B Jr, Gröger AM, Siegel SE and Kaiser HE: Invasion and metastasis: The expression and significance of matrix metalloproteinases in carcinomas of the lung. In Vivo. 15:175–180. 2001.PubMed/NCBI
7	Dhillon AS, Hagan S, Rath O and Kolch W: MAP kinase signalling pathways in cancer. Oncogene. 26:3279–3290. 2007. View Article : Google Scholar : PubMed/NCBI
8	Trusolino L and Comoglio PM: Scatter-factor and semaphorin receptors: Cell signalling for invasive growth. Nat Rev Cancer. 2:289–300. 2002. View Article : Google Scholar : PubMed/NCBI
9	Noh EM, Park YJ, Kim JM, Kim MS, Kim HR, Song HK, Hong OY, So HS, Yang SH, Kim JS, et al: Fisetin regulates TPA-induced breast cell invasion by suppressing matrix metalloproteinase-9 activation via the PKC/ROS/MAPK pathways. Eur J Pharmacol. 764:79–86. 2015. View Article : Google Scholar : PubMed/NCBI
10	Xia P, Zhang R and Ge G: C/EBPβ mediates TNF-α-induced cancer cell migration by inducing MMP expression dependent on p38 MAPK. J Cell Biochem. 116:2766–2777. 2015. View Article : Google Scholar : PubMed/NCBI
11	Liu ZL, Liu Q, Xiao B, Zhou J, Zhang JG and Li Y: The vascular protective properties of kinsenoside isolated from Anoectochilus roxburghii under high glucose condition. Fitoterapia. 86:163–170. 2013. View Article : Google Scholar : PubMed/NCBI
12	Schmidt TJ, Brun R, Willuhn G and Khalid SA: Antitrypanosomal activity of helenalin and some structurally related sesquiterpene lactones. Planta Med. 68:750–751. 2002. View Article : Google Scholar : PubMed/NCBI
13	Di W, Khan M, Rasul A, Sun M, Sui Y, Zhong L, Yang L, Zhu Q, Feng L and Ma T: Isoalantolactone inhibits constitutive NF-κB activation and induces reactive oxygen species-mediated apoptosis in osteosarcoma U2OS cells through mitochondrial dysfunction. Oncol Rep. 32:1585–1593. 2014.PubMed/NCBI
14	Stojanović-Radić Z, Comić Lj, Radulović N, Blagojević P, Denić M, Miltojević A, Rajković J and Mihajilov-Krstev T: Antistaphylococcal activity of Inula helenium L. root essential oil: Eudesmane sesquiterpene lactones induce cell membrane damage. Eur J Clin Microbiol Infect Dis. 31:1015–1025. 2012. View Article : Google Scholar
15	Kumar A, Kumar S, Kumar D and Agnihotri VK: UPLC/MS/MS method for quantification and cytotoxic activity of sesquiterpene lactones isolated from Saussurea lappa. J Ethnopharmacol. 155:1393–1397. 2014. View Article : Google Scholar : PubMed/NCBI
16	Wu M, Zhang H, Hu J, Weng Z, Li C, Li H, Zhao Y, Mei X, Ren F and Li L: Isoalantolactone inhibits UM-SCC-10A cell growth via cell cycle arrest and apoptosis induction. PLoS One. 8:e760002013. View Article : Google Scholar : PubMed/NCBI
17	Rasul A, Di J, Millimouno FM, Malhi M, Tsuji I, Ali M, Li J and Li X: Reactive oxygen species mediate isoalantolactone-induced apoptosis in human prostate cancer cells. Molecules. 18:9382–9396. 2013. View Article : Google Scholar : PubMed/NCBI
18	Rasul A, Khan M, Yu B, Ali M, Bo YJ, Yang H and Ma T: Isoalantolactone, a sesquiterpene lactone, induces apoptosis in SGC-7901 cells via mitochondrial and phosphatidylinositol 3-kinase/Akt signaling pathways. Arch Pharm Res. 36:1262–1269. 2013. View Article : Google Scholar : PubMed/NCBI
19	Zhang C, Chi YL, Wang PY, Wang YQ, Zhang YX, Deng J, Lv CJ and Xie SY: miR-511 and miR-1297 inhibit human lung adenocarcinoma cell proliferation by targeting oncogene TRIB2. PLoS One. 7:e460902012. View Article : Google Scholar : PubMed/NCBI
20	Wu W, He X, Kong J and Ye B: mir-373 affects human lung cancer cells' growth and its E-cadherin expression. Oncol Res. 20:163–170. 2012. View Article : Google Scholar : PubMed/NCBI
21	Albini A, Benelli R, Noonan DM and Brigati C: The 'chemoinvasion assay': A tool to study tumor and endothelial cell invasion of basement membranes. Int J Dev Biol. 48:563–571. 2004. View Article : Google Scholar
22	Feng L, Zhu MM, Zhang MH, Wang RS, Tan XB, Song J, Ding SM, Jia XB and Hu SY: Protection of glycyrrhizic acid against AGEs-induced endothelial dysfunction through inhibiting RAGE/NF-κB pathway activation in human umbilical vein endothelial cells. J Ethnopharmacol. 148:27–36. 2013. View Article : Google Scholar : PubMed/NCBI
23	Wang L, Ling Y, Chen Y, Li CL, Feng F, You QD, Lu N and Guo QL: Flavonoid baicalein suppresses adhesion, migration and invasion of MDA-MB-231 human breast cancer cells. Cancer Lett. 297:42–48. 2010. View Article : Google Scholar : PubMed/NCBI
24	Reddy KB, Nabha SM and Atanaskova N: Role of MAP kinase in tumor progression and invasion. Cancer Metastasis Rev. 22:395–403. 2003. View Article : Google Scholar : PubMed/NCBI
25	Wang S, Liu Q, Zhang Y, Liu K, Yu P, Liu K, Luan J, Duan H, Lu Z, Wang F, et al: Suppression of growth, migration and invasion of highly-metastatic human breast cancer cells by berbamine and its molecular mechanisms of action. Mol Cancer. 8:812009. View Article : Google Scholar : PubMed/NCBI
26	Xu E, Zhao J, Ma J, Wang C, Zhang C, Jiang H, Cheng J, Gao R and Zhou X: miR-146b-5p promotes invasion and metastasis contributing to chemoresistance in osteosarcoma by targeting zinc and ring finger 3. Oncol Rep. 35:275–283. 2016.
27	Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T and Thun MJ: Cancer statistics, 2008. CA Cancer J Clin. 58:71–96. 2008. View Article : Google Scholar : PubMed/NCBI
28	McCawley LJ and Matrisian LM: Matrix metalloproteinases: Multifunctional contributors to tumor progression. Mol Med Today. 6:149–156. 2000. View Article : Google Scholar : PubMed/NCBI
29	Yan C and Boyd DD: Regulation of matrix metalloproteinase gene expression. J Cell Physiol. 211:19–26. 2007. View Article : Google Scholar
30	Kim JH, Yang YI, Ahn JH, Lee JG, Lee KT and Choi JH: Deer (Cervus elaphus) antler extract suppresses adhesion and migration of endometriotic cells and regulates MMP-2 and MMP-9 expression. J Ethnopharmacol. 140:391–397. 2012. View Article : Google Scholar : PubMed/NCBI
31	Yang SF, Chen MK, Hsieh YS, Yang JS, Zavras AI, Hsieh YH, Su SC, Kao TY, Chen PN and Chu SC: Antimetastatic effects of Terminalia catappa L. on oral cancer via a down-regulation of metastasis-associated proteases. Food Chem Toxicol. 48:1052–1058. 2010. View Article : Google Scholar : PubMed/NCBI
32	Puricelli L, Dell'Aica I, Sartor L, Garbisa S and Caniato R: Preliminary evaluation of inhibition of matrix-metalloprotease MMP-2 and MMP-9 by Passiflora edulis and P. foetida aqueous extracts. Fitoterapia. 74:302–304. 2003. View Article : Google Scholar : PubMed/NCBI
33	Niu J, Huang Y and Zhang L: CXCR4 silencing inhibits invasion and migration of human laryngeal cancer Hep-2 cells. Int J Clin Exp Pathol. 8:6255–6261. 2015.PubMed/NCBI
34	Zhan Y, Zhang H, Liu R, Wang W, Qi J and Zhang Y: Eupolyphaga sinensis Walker ethanol extract suppresses cell growth and invasion in human breast cancer cells. Integr Cancer Ther. 15:102–112. 2016. View Article : Google Scholar
35	Chen Y, Zheng L, Liu J, Zhou Z, Cao X, Lv X and Chen F: Shikonin inhibits prostate cancer cells metastasis by reducing matrix metalloproteinase-2/-9 expression via AKT/mTOR and ROS/ERK1/2 pathways. Int Immunopharmacol. 21:447–455. 2014. View Article : Google Scholar : PubMed/NCBI
36	Lu L, Zhang Q, Wu K, Chen X, Zheng Y, Zhu C and Wu J: Hepatitis C virus NS3 protein enhances cancer cell invasion by activating matrix metalloproteinase-9 and cyclooxygenase-2 through ERK/p38/NF-κB signal cascade. Cancer Lett. 356:470–478. 2015. View Article : Google Scholar
37	Cui XP, Qin CK, Zhang ZH, Su ZX, Liu X, Wang SK and Tian XS: HOXA10 promotes cell invasion and MMP-3 expression via TGFβ2-mediated activation of the p38 MAPK pathway in pancreatic cancer cells. Dig Dis Sci. 59:1442–1451. 2014. View Article : Google Scholar : PubMed/NCBI
38	Kim D, Kim S, Koh H, Yoon SO, Chung AS, Cho KS and Chung J: Akt/PKB promotes cancer cell invasion via increased motility and metalloproteinase production. FASEB J. 15:1953–1962. 2001. View Article : Google Scholar : PubMed/NCBI
39	Xu P, Cai F, Liu X and Guo L: Sesamin inhibits lipopolysaccharide-induced proliferation and invasion through the p38-MAPK and NF-κB signaling pathways in prostate cancer cells. Oncol Rep. 33:3117–3123. 2015.PubMed/NCBI