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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

Syringic Acid Suppressed Proliferation, Invasion, and Migration via Inhibition of Matrix Metalloproteinases Expression on Glioblastoma Cells by Promoting Apoptosis

Author(s): Dan Li, Dongdong Luo, Su Hu, Hailin Zhao and Biao Peng*

Volume 24, Issue 2, 2023

Published on: 02 August, 2022

Page: [310 - 316] Pages: 7

DOI: 10.2174/1389201023666220513100129

Price: $65

Abstract

Background: Human brain tumor glioblastoma (GBM) is the most hostile malignancy, currently lacking a successful cure and good prognosis.

Objective: To examine the anticancer effects of syringic acid (SA) on human cancer GBM cells.

Methodology: The different doses of SA were added to GBM cells to study its effect on viability, invasion, relocation, apoptosis, and mRNA and protein levels. Hence, we explored the antiproliferative, anti-invasive, and apoptotic activity of SA on GBM human U-251 cells.

Results: MTT assay and live/dead assay revealed the anti-proliferative activity of SA on U-251 glioma cells. Apoptotic activity of SA was shown by DAPI staining, caspase-3, Bax, and Bcl-2 mRNA expressions. The cell cycle regulation was also confirmed by reducing the mRNA expression of cyclinD1, CDK4, and CDK6. Treatment of SA with U-251 cells suppressed MMPs expressions and enhanced TIMPs protein levels.

Conclusion: Our findings put forward that SA could prevent GBM cells’ invasion and relocation. SA is an ideal neuroprotective agent for controlling brain malignancy.

Keywords: Glioblastoma, syringic acid, proliferation, invasion, apoptosis, cell toxicity.

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Graphical Abstract

[1]
Stupp, R. European organisation for research and treatment of cancer brain tumor and radiotherapy groups; National Cancer Institute of Canada clinical trials group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med., 2005, 352(10), 987-996.
[http://dx.doi.org/10.1056/NEJMoa043330] [PMID: 15758009]
[2]
Wen, P.Y.; Kesari, S. Malignant gliomas in adults. N. Engl. J. Med., 2008, 359(5), 492-507.
[http://dx.doi.org/10.1056/NEJMra0708126] [PMID: 18669428]
[3]
Stupp, R.; Hegi, M.E.; Mason, W.P.; van den Bent, M.J.; Taphoorn, M.J.; Janzer, R.C.; Ludwin, S.K.; Allgeier, A.; Fisher, B.; Belanger, K.; Hau, P.; Brandes, A.A.; Gijtenbeek, J.; Marosi, C.; Vecht, C.J.; Mokhtari, K.; Wesseling, P.; Villa, S.; Eisenhauer, E.; Gorlia, T.; Weller, M.; Lacombe, D.; Cairncross, J.G.; Mirimanoff, R.O. European Organisation for Research and Treatment of Cancer brain tumour and radiation oncology groups; National Cancer Institute of Canada clinical trials group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol., 2009, 10(5), 459-466.
[http://dx.doi.org/10.1016/S1470-2045(09)70025-7] [PMID: 19269895]
[4]
Kleihues, P.; Louis, D.N.; Scheithauer, B.W.; Rorke, L.B.; Reifenberger, G.; Burger, P.C.; Cavenee, W.K. The WHO classification of tumors of the nervous system. J. Neuropathol. Exp. Neurol., 2002, 61(3), 215-225.
[http://dx.doi.org/10.1093/jnen/61.3.215] [PMID: 11895036]
[5]
Steeg, P.S. Tumor metastasis: Mechanistic insights and clinical challenges. Nat. Med., 2006, 12(8), 895-904.
[http://dx.doi.org/10.1038/nm1469] [PMID: 16892035]
[6]
Wan, L.; Pantel, K.; Kang, Y. Tumor metastasis: Moving new biological insights into the clinic. Nat. Med., 2013, 19(11), 1450-1464.
[http://dx.doi.org/10.1038/nm.3391] [PMID: 24202397]
[7]
Fillmore, H.L.; VanMeter, T.E.; Broaddus, W.C. Membrane-type matrix metalloproteinases (MT-MMPs): Expression and function during glioma invasion. J. Neurooncol., 2001, 53(2), 187-202.
[http://dx.doi.org/10.1023/A:1012213604731] [PMID: 11716070]
[8]
Egeblad, M.; Werb, Z. New functions for the matrix metalloproteinases in cancer progression. Nat. Rev. Cancer, 2002, 2(3), 161-174.
[http://dx.doi.org/10.1038/nrc745] [PMID: 11990853]
[9]
Hua, H.; Li, M.; Luo, T.; Yin, Y.; Jiang, Y. Matrix metalloproteinases in tumorigenesis: An evolving paradigm. Cell. Mol. Life Sci., 2011, 68(23), 3853-3868.
[http://dx.doi.org/10.1007/s00018-011-0763-x] [PMID: 21744247]
[10]
Salhia, B.; Tran, N.L.; Chan, A.; Wolf, A.; Nakada, M.; Rutka, F.; Ennis, M.; McDonough, W.S.; Berens, M.E.; Symons, M.; Rutka, J.T. The guanine nucleotide exchange factors trio, Ect2, and Vav3 mediate the invasive behavior of glioblastoma. Am. J. Pathol., 2008, 173(6), 1828-1838.
[http://dx.doi.org/10.2353/ajpath.2008.080043] [PMID: 19008376]
[11]
Maiuri, M.C.; Zalckvar, E.; Kimchi, A.; Kroemer, G. Self-eating and self-killing: Crosstalk between autophagy and apoptosis. Nat. Rev. Mol. Cell Biol., 2007, 8(9), 741-752.
[http://dx.doi.org/10.1038/nrm2239] [PMID: 17717517]
[12]
Ghobrial, I.M.; Witzig, T.E.; Adjei, A.A. Targeting apoptosis pathways in cancer therapy. CA Cancer J. Clin., 2005, 55(3), 178-194.
[http://dx.doi.org/10.3322/canjclin.55.3.178] [PMID: 15890640]
[13]
Catchpoole, D.R.; Lock, R.B. The potential tumour suppressor role for caspase-9 (CASP9) in the childhood malignancy, neuroblastoma. Eur. J. Cancer, 2001, 37(17), 2217-2221.
[http://dx.doi.org/10.1016/S0959-8049(01)00273-8] [PMID: 11677110]
[14]
Green, D.R.; Kroemer, G. The pathophysiology of mitochondrial cell death. Science, 2004, 305(5684), 626-629.
[http://dx.doi.org/10.1126/science.1099320] [PMID: 15286356]
[15]
Lee, W.J.; Chen, W.K.; Wang, C.J.; Lin, W.L.; Tseng, T.H. Apigenin inhibits HGF-promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and beta 4 integrin function in MDA-MB-231 breast cancer cells. Toxicol. Appl. Pharmacol., 2008, 226(2), 178-191.
[http://dx.doi.org/10.1016/j.taap.2007.09.013] [PMID: 17961621]
[16]
Shi, C; Sun, Y; Zheng, Z Antimicrobial activity of syringic acid against Cronobacter sakazakii and its effect on cell membrane. Food Chem., 2016, 197(Pt A), 100-106.
[http://dx.doi.org/10.1016/j.foodchem.2015.10.100]
[17]
Srinivasulu, C.; Ramgopal, M.; Ramanjaneyulu, G.; Anuradha, C.M.; Suresh Kumar, C. Syringic acid (SA) ‒ A review of its occurrence, biosynthesis, pharmacological and industrial importance. Biomed. Pharmacothe., 2018, 108, 547-557.
[http://dx.doi.org/10.1016/j.biopha.2018.09.069] [PMID: 30243088]
[18]
Domínguez Avila, J.A.; Rodrigo García, J.; González Aguilar, G.A.; de la Rosa, L.A. The antidiabetic mechanisms of polyphenols related to increased Glucagon-Like Peptide-1 (GLP1) and insulin signaling. Molecules, 2017, 22(6), 903.
[http://dx.doi.org/10.3390/molecules22060903] [PMID: 28556815]
[19]
John, C.M.; Arockiasamy, S. Syringic acid (4-hydroxy-3,5-dimethoxybenzoic acid) inhibits adipogenesis and promotes lipolysis in 3T3-L1 adipocytes. Nat. Prod. Res., 2020, 34(23), 3432-3436.
[http://dx.doi.org/10.1080/14786419.2019.1573820] [PMID: 30777451]
[20]
Tokmak, M.; Sehitoglu, M.H.; Yuksel, Y.; Guven, M.; Akman, T.; Aras, A.B.; Yaka, U.; Gomleksiz, C.; Albayrak, S.B.; Cosar, M. The axon protective effects of syringic acid on ischemia/reperfusion injury in a rat sciatic nerve model. Turk Neurosurg., 2017, 27(1), 124-132.
[PMID: 27593755]
[21]
Davis, M.E. Glioblastoma: Overview of disease and treatment. Clin. J. Oncol. Nurs., 2016, 20(5)(Suppl.), S2-S8.
[http://dx.doi.org/10.1188/16.CJON.S1.2-8] [PMID: 27668386]
[22]
Astner, S.T.; Pihusch, R.; Nieder, C.; Rachinger, W.; Lohner, H.; Tonn, J.C.; Molls, M.; Grosu, A.L. Extensive local and systemic therapy in extraneural metastasized glioblastoma multiforme. Anticancer Res., 2006, 26(6C), 4917-4920.
[PMID: 17214362]
[23]
Vermeulen, K.; Van Bockstaele, D.R.; Berneman, Z.N. The cell cycle: A review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif., 2003, 36(3), 131-149.
[http://dx.doi.org/10.1046/j.1365-2184.2003.00266.x] [PMID: 12814430]
[24]
Hosoda, A.; Ozaki, Y.; Kashiwada, A.; Mutoh, M.; Wakabayashi, K.; Mizuno, K.; Nomura, E.; Taniguchi, H. Syntheses of ferulic acid derivatives and their suppressive effects on cyclooxygenase-2 promoter activity. Bioorg. Med. Chem., 2002, 10(4), 1189-1196.
[http://dx.doi.org/10.1016/S0968-0896(01)00386-8] [PMID: 11836130]
[25]
Abaza, M.S.; Al-Attiyah, R.; Bhardwaj, R.; Abbadi, G.; Koyippally, M.; Afzal, M. Syringic acid from Tamarix aucheriana possesses antimitogenic and chemo-sensitizing activities in human colorectal cancer cells. Pharm. Biol., 2013, 51(9), 1110-1124.
[http://dx.doi.org/10.3109/13880209.2013.781194] [PMID: 23745612]
[26]
Danial, N.N.; Korsmeyer, S.J. Cell death: Critical control points. Cell, 2004, 116(2), 205-219.
[http://dx.doi.org/10.1016/S0092-8674(04)00046-7] [PMID: 14744432]
[27]
Brown, J.M.; Attardi, L.D. The role of apoptosis in cancer development and treatment response. Nat. Rev. Cancer, 2005, 5(3), 231-237.
[http://dx.doi.org/10.1038/nrc1560] [PMID: 15738985]
[28]
Boise, L.H.; González-García, M.; Postema, C.E.; Ding, L.; Lindsten, T.; Turka, L.A.; Mao, X.; Nuñez, G.; Thompson, C.B. bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell, 1993, 74(4), 597-608.
[http://dx.doi.org/10.1016/0092-8674(93)90508-N] [PMID: 8358789]
[29]
Yin, C.; Knudson, C.M.; Korsmeyer, S.J.; Van Dyke, T. Bax suppresses tumorigenesis and stimulates apoptosis in vivo. Nature, 1997, 385(6617), 637-640.
[http://dx.doi.org/10.1038/385637a0] [PMID: 9024662]
[30]
Evan, G.I.; Vousden, K.H. Proliferation, cell cycle and apoptosis in cancer. Nature, 2001, 411(6835), 342-348.
[http://dx.doi.org/10.1038/35077213] [PMID: 11357141]
[31]
McCall, B.; McPartland, C.K.; Moore, R.; Frank-Kamenetskii, A.; Booth, B.W. Effects of astaxanthin on the proliferation and migration of breast cancer cells in vitro. Antioxidants, 2018, 7(10), 135.
[http://dx.doi.org/10.3390/antiox7100135] [PMID: 30287735]
[32]
Douglas, D.A.; Shi, Y.E.; Sang, Q.A. Computational sequence analysis of the tissue inhibitor of metalloproteinase family. J. Protein Chem., 1997, 16(4), 237-255.
[http://dx.doi.org/10.1023/A:1026348808069] [PMID: 9188064]
[33]
Deryugina, E.I.; Quigley, J.P. Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev., 2006, 25(1), 9-34.
[http://dx.doi.org/10.1007/s10555-006-7886-9] [PMID: 16680569]

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