Login Register Cart 0
Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Research Article

Mogroside V Inhibits Hyperglycemia-induced Lung Cancer Cells Metastasis through Reversing EMT and Damaging Cytoskeleton

Author(s): Jun Chen, Demin Jiao, Yu Li, Chunyan Jiang, Xiali Tang, Jia Song and Qingyong Chen*

Volume 19, Issue 11, 2019

Page: [885 - 895] Pages: 11

DOI: 10.2174/1568009619666190619154240

Price: $65

Abstract

Background: Diabetes Mellitus (DM) accelerates progress of lung cancer. Hyperglycemia, a critical feature of DM, promotes lung cancer metastasis. Mogroside V is a triterpenoid glycoside from Siraitia grosvenorii. Interestingly, mogroside V not only plays an anti-diabetic role, but also has anti-tumor effects.

Objective: In this study, we investigated the metastatic efficiency of mogroside V in lung cancer cells cultured in hyperglycemia.

Methods: Two lung cancer cell lines-A549 and H1299 were cultured in normoglycemia (5.5mM glucose) and hyperglycemia (25mM glucose). Cellular proliferation was tested by MTT, invasion was examined by transwell assay, migration was measured by wound healing assay, cytoskeleton was stained by Phalloidin-TRITC and the expressions of EMT markers and Rho-GTPase family protein were detected by western blot.

Results: Hyperglycemia promoted the invasion and migration of A549 and H1299 cells compared with normoglycemia. Mogroside V inhibited the hyperglycemia-induced invasion and migration. Hyperglycemia promoted epithelial-mesenchymal transition (EMT), while mogroside V could reverse this process through up-regulating E-Cadherin expression and down-regulating N-Cadherin, Vimentin, Snail expressions. Furthermore, mogroside V fractured microfilaments and reduced Rho A, Rac1, Cdc42 and p-PAK1 expressions under hyperglycemic conditions.

Conclusion: These results suggest that mogroside V inhibits hyperglycemia-induced lung cancer cells migration and invasion through reversing EMT and damaging cytoskeleton.

Keywords: Mogroside V, hyperglycemia, metastasis, EMT, cytoskeleton, lung cancer.

« Previous Next »
Graphical Abstract

[1]
Iarrobino, N.A.; Gill, B.S.; Bernard, M.; Klement, R.J.; Werner-Wasik, M.; Champ, C.E. The impact of serum glucose, anti-diabetic agents, and statin usage in non-small cell lung cancer patients treated with definitive chemoradiation. Front. Oncol., 2018, 8, 281.
[http://dx.doi.org/10.3389/fonc.2018.00281] [PMID: 30101126]
[2]
Kurishima, K.; Watanabe, H.; Ishikawa, H.; Satoh, H.; Hizawa, N. Survival of patients with lung cancer and diabetes mellitus. Mol. Clin. Oncol., 2017, 6(6), 907-910.
[http://dx.doi.org/10.3892/mco.2017.1224] [PMID: 28588788]
[3]
Xu, T.; Li, D.; He, Y.; Zhang, F.; Qiao, M.; Chen, Y. Prognostic value of metformin for non-small cell lung cancer patients with diabetes. World J. Surg. Oncol., 2018, 16(1), 60.
[http://dx.doi.org/10.1186/s12957-018-1362-1] [PMID: 29558957]
[4]
Wu, K.; Yu, X.; Huang, Z.; Zhu, D.; Yi, X.; Wu, Y. L.; Hao, Q.; Kemp, K. T., 2nd; Elshimali, Y.; Iyer, R.; Nguyen, K. T.; Zheng, S.; Chen, G.; Chen, Q. H.; Wang, G.; Vadgama, J. V.; Wu, Y. Targeting of PP2Cdelta by a small molecule C23 inhibits high glucoseinduced breast cancer progression in vivo. Antioxidants & redox signaling, 2018.
[5]
Kellenberger, L.D.; Petrik, J. Hyperglycemia promotes insulin-independent ovarian tumor growth. Gynecol. Oncol., 2018, 149(2), 361-370.
[http://dx.doi.org/10.1016/j.ygyno.2018.02.003] [PMID: 29458977]
[6]
Li, X.; Li, J.; Cai, Y.; Peng, S.; Wang, J.; Xiao, Z.; Wang, Y.; Tao, Y.; Li, J.; Leng, Q.; Wu, D.; Yang, S.; Ji, Z.; Han, Y.; Li, L.; Gao, X.; Zeng, C.; Wen, X. Hyperglycaemia-induced miR-301a promotes cell proliferation by repressing p21 and Smad4 in prostate cancer. Cancer Lett., 2018, 418, 211-220.
[http://dx.doi.org/10.1016/j.canlet.2018.01.031] [PMID: 29331421]
[7]
Wu, H.; Zhang, T.; Pan, F.; Steer, C.J.; Li, Z.; Chen, X.; Song, G. MicroRNA-206 prevents hepatosteatosis and hyperglycemia by facilitating insulin signaling and impairing lipogenesis. J. Hepatol., 2017, 66(4), 816-824.
[http://dx.doi.org/10.1016/j.jhep.2016.12.016] [PMID: 28025059]
[8]
Kang, X.; Kong, F.; Wu, X.; Ren, Y.; Wu, S.; Wu, K.; Jiang, Z.; Zhang, W. High glucose promotes tumor invasion and increases metastasis-associated protein expression in human lung epithelial cells by upregulating heme oxygenase-1 via reactive oxygen species or the TGF-β1/PI3K/Akt signaling pathway. Cell. Physiol. Biochem., 2015, 35(3), 1008-1022.
[http://dx.doi.org/10.1159/000373928] [PMID: 25661467]
[9]
Rahn, S.; Zimmermann, V.; Viol, F.; Knaack, H.; Stemmer, K.; Peters, L.; Lenk, L.; Ungefroren, H.; Saur, D.; Schäfer, H.; Helm, O.; Sebens, S. Diabetes as risk factor for pancreatic cancer: Hyperglycemia promotes epithelial-mesenchymal-transition and stem cell properties in pancreatic ductal epithelial cells. Cancer Lett., 2018, 415, 129-150.
[http://dx.doi.org/10.1016/j.canlet.2017.12.004] [PMID: 29222037]
[10]
Xu, X.; Si, M.; Lou, H.; Yan, Y.; Liu, Y.; Zhu, H.; Lou, X.; Ma, J.; Zhu, D.; Wu, H.; Yang, B.; Wu, H.; Ding, L.; He, Q. Hyperglycemia decreases anti-cancer efficiency of Adriamycin via AMPK pathway. Endocr. Relat. Cancer, 2018, ERC-18-ERC-0036.
[http://dx.doi.org/10.1530/ERC-18-0036] [PMID: 29941677]
[11]
Talakatta, G.; Sarikhani, M.; Muhamed, J.; Dhanya, K.; Somashekar, B.S.; Mahesh, P.A.; Sundaresan, N.; Ravindra, P.V. Diabetes induces fibrotic changes in the lung through the activation of TGF-β signaling pathways. Sci. Rep., 2018, 8(1), 11920.
[http://dx.doi.org/10.1038/s41598-018-30449-y] [PMID: 30093732]
[12]
Pawar, R.S.; Krynitsky, A.J.; Rader, J.I. Sweeteners from plants with emphasis on Stevia rebaudiana (Bertoni) and Siraitia grosvenorii (Swingle). Anal. Bioanal. Chem., 2013, 405(13), 4397-4407.
[http://dx.doi.org/10.1007/s00216-012-6693-0] [PMID: 23341001]
[13]
Xiangyang, Q.; Weijun, C.; Liegang, L.; Ping, Y.; Bijun, X. Effect of a Siraitia grosvenori extract containing mogrosides on the cellular immune system of type 1 diabetes mellitus mice. Mol. Nutr. Food Res., 2006, 50(8), 732-738.
[http://dx.doi.org/10.1002/mnfr.200500252] [PMID: 16835866]
[14]
Itkin, M.; Davidovich-Rikanati, R.; Cohen, S.; Portnoy, V.; Doron-Faigenboim, A.; Oren, E.; Freilich, S.; Tzuri, G.; Baranes, N.; Shen, S.; Petreikov, M.; Sertchook, R.; Ben-Dor, S.; Gottlieb, H.; Hernandez, A.; Nelson, D.R.; Paris, H.S.; Tadmor, Y.; Burger, Y.; Lewinsohn, E.; Katzir, N.; Schaffer, A. The biosynthetic pathway of the nonsugar, high-intensity sweetener mogroside V from Siraitia grosvenorii. Proc. Natl. Acad. Sci. USA, 2016, 113(47), E7619-E7628.
[http://dx.doi.org/10.1073/pnas.1604828113] [PMID: 27821754]
[15]
Takasaki, M.; Konoshima, T.; Murata, Y.; Sugiura, M.; Nishino, H.; Tokuda, H.; Matsumoto, K.; Kasai, R.; Yamasaki, K. Anticarcinogenic activity of natural sweeteners, cucurbitane glycosides, from Momordica grosvenori. Cancer Lett., 2003, 198(1), 37-42.
[http://dx.doi.org/10.1016/S0304-3835(03)00285-4] [PMID: 12893428]
[16]
Liu, C.; Dai, L.H.; Dou, D.Q.; Ma, L.Q.; Sun, Y.X. A natural food sweetener with anti-pancreatic cancer properties. Oncogenesis, 2016. 5e217
[http://dx.doi.org/10.1038/oncsis.2016.28] [PMID: 27065453]
[17]
Wu, D.; Hu, D.; Chen, H.; Shi, G.; Fetahu, I.S.; Wu, F.; Rabidou, K.; Fang, R.; Tan, L.; Xu, S.; Liu, H.; Argueta, C.; Zhang, L.; Mao, F.; Yan, G.; Chen, J.; Dong, Z.; Lv, R.; Xu, Y.; Wang, M.; Ye, Y.; Zhang, S.; Duquette, D.; Geng, S.; Yin, C.; Lian, C.G.; Murphy, G.F.; Adler, G.K.; Garg, R.; Lynch, L.; Yang, P.; Li, Y.; Lan, F.; Fan, J.; Shi, Y.; Shi, Y.G. Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer. Nature, 2018, 559(7715), 637-641.
[http://dx.doi.org/10.1038/s41586-018-0350-5] [PMID: 30022161]
[18]
Srivastava, K.; Shao, B.; Bayraktutan, U. PKC-β exacerbates in vitro brain barrier damage in hyperglycemic settings via regulation of RhoA/Rho-kinase/MLC2 pathway. J. Cereb. Blood Flow Metab., 2013, 33(12), 1928-1936.
[http://dx.doi.org/10.1038/jcbfm.2013.151] [PMID: 23963366]
[19]
Gu, C.J.; Xie, F.; Zhang, B.; Yang, H.L.; Cheng, J.; He, Y.Y.; Zhu, X.Y.; Li, D.J.; Li, M.Q. High glucose promotes epithelial-mesenchymal transition of uterus endometrial cancer cells by increasing ER/GLUT4-mediated VEGF secretion. Cell. Physiol. Biochem., 2018, 50(2), 706-720.
[http://dx.doi.org/10.1159/000494237] [PMID: 30308493]
[20]
Ho, Y.; Chen, Y.F.; Wang, L.H.; Hsu, K.Y.; Chin, Y.T.; Yang, Y.S.H.; Wang, S.H.; Chen, Y.R.; Shih, Y.J.; Liu, L.F.; Wang, K.; Whang-Peng, J.; Tang, H.Y.; Lin, H.Y.; Liu, H.L.; Lin, S.J. Inhibitory effect of Anoectochilus formosanus extract on hyperglycemia-related PD-L1 expression and cancer proliferation. Front. Pharmacol., 2018, 9, 807.
[http://dx.doi.org/10.3389/fphar.2018.00807] [PMID: 30116189]
[21]
Chakroun, M.; Khemakhem, B.; Mabrouk, H.B.; El Abed, H.; Makni, M.; Bouaziz, M.; Drira, N.; Marrakchi, N.; Mejdoub, H. Evaluation of anti-diabetic and anti-tumoral activities of bioactive compounds from Phoenix dactylifera L’s leaf: In vitro and in vivo approach. Biomed. Pharmacother., 2016, 84, 415-422.
[http://dx.doi.org/10.1016/j.biopha.2016.09.062] [PMID: 27668542]
[22]
Liu, H.; Qi, X.; Yu, K.; Lu, A.; Lin, K.; Zhu, J.; Zhang, M.; Sun, Z. AMPK activation is involved in hypoglycemic and hypolipidemic activities of mogroside-rich extract from Siraitia grosvenorii (Swingle) fruits on high-fat diet/streptozotocin-induced diabetic mice. Food Funct., 2019, 10(1), 151-162.
[http://dx.doi.org/10.1039/C8FO01486H] [PMID: 30516208]
[23]
Zhang, X.; Song, Y.; Ding, Y.; Wang, W.; Liao, L.; Zhong, J.; Sun, P.; Lei, F.; Zhang, Y.; Xie, W. Effects of mogrosides on high-fat-diet-induced obesity and nonalcoholic fatty liver disease in mice. Molecules, 2018, 23(8), 1894.
[http://dx.doi.org/10.3390/molecules23081894] [PMID: 30060618]
[24]
Ding, C.Z.; Guo, X.F.; Wang, G.L.; Wang, H.T.; Xu, G.H.; Liu, Y.Y.; Wu, Z.J.; Chen, Y.H.; Wang, J.; Wang, W.G. High glucose contributes to the proliferation and migration of non-small cell lung cancer cells via GAS5-TRIB3 axis. Biosci. Rep., 2018.BSR20171014
[http://dx.doi.org/10.1042/BSR20171014] [PMID: 29367413]
[25]
Li, W.; Liu, H.; Qian, W.; Cheng, L.; Yan, B.; Han, L.; Xu, Q.; Ma, Q.; Ma, J. Hyperglycemia aggravates microenvironment hypoxia and promotes the metastatic ability of pancreatic cancer. Comput. Struct. Biotechnol. J., 2018, 16, 479-487.
[http://dx.doi.org/10.1016/j.csbj.2018.10.006] [PMID: 30455857]
[26]
Diepenbruck, M.; Christofori, G. Epithelial-mesenchymal transition (EMT) and metastasis: Yes, no, maybe? Curr. Opin. Cell Biol., 2016, 43, 7-13.
[http://dx.doi.org/10.1016/j.ceb.2016.06.002] [PMID: 27371787]
[27]
Chaffer, C.L.; San Juan, B.P.; Lim, E.; Weinberg, R.A. EMT, cell plasticity and metastasis. Cancer Metastasis Rev., 2016, 35(4), 645-654.
[http://dx.doi.org/10.1007/s10555-016-9648-7] [PMID: 27878502]
[28]
Sousa-Squiavinato, A.C.M.; Rocha, M.R.; Barcellos-de-Souza, P.; de Souza, W.F.; Morgado-Diaz, J.A. Cofilin-1 signaling mediates epithelial-mesenchymal transition by promoting actin cytoskeleton reorganization and cell-cell adhesion regulation in colorectal cancer cells. Biochim. Biophys. Acta Mol. Cell Res., 2019, 1866(3), 418-429.
[http://dx.doi.org/10.1016/j.bbamcr.2018.10.003] [PMID: 30296500]
[29]
Lv, Z.; Hu, M.; Zhen, J.; Lin, J.; Wang, Q.; Wang, R. Rac1/PAK1 signaling promotes epithelial-mesenchymal transition of podocytes in vitro via triggering β-catenin transcriptional activity under high glucose conditions. Int. J. Biochem. Cell Biol., 2013, 45(2), 255-264.
[http://dx.doi.org/10.1016/j.biocel.2012.11.003] [PMID: 23153508]

Rights & Permissions Print Cite
Article Metrics
97
3
© 2024 Bentham Science Publishers | Privacy Policy