Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

In Vitro Effects of Propofol on Cytotoxic, Apoptotic and PI3K-Akt Signaling Pathway Genes on Brain Cancer Cells

Author(s): Tuba Gokdogan Edgunlu, Cigir Biray Avci*, Neslihan Pınar Ozates, Bakiye Goker Bagca, Sevim Karakas Celik, Aydin Boluk and Bakiye Ugur

Volume 22, Issue 2, 2022

Published on: 30 December, 2021

Page: [356 - 361] Pages: 6

DOI: 10.2174/1871520621666210708094328

Price: $65

Abstract

Aim: The study aimed to determine the cytotoxic and apoptotic effect of propofol on glioma cells.

Background: Propofol [2,6-diisopropylphenol] is a commonly used intravenous anesthetic. Propofol is known to have a mechanism of action on the PI3K-AKT pathway.

Objective: This study aimed to evaluate the effect of propofol on the proliferation and apoptosis of human glioma cells, as well as to investigate changes in expression levels of the PI3K-AKT signaling pathway genes.

Materials and Methods: The cytotoxic effect of propofol on the U-87 MG cell line was determined by WST-1 method. Annexin V-FITC and Mitoprobe JC-1 assay were used to measure apoptosis by flow cytometry. The expression levels of genes in the PI3K-AKT signaling pathway were investigated by qRT-PCR.

Results: We have shown that propofol induced apoptosis in U-87 MG cells by 17.1 fold compared to the untreated control. Furthermore, significant differences were found in the expression levels of the PI3K-AKT signaling pathway genes.

Conclusion: As a result of our study, it was found that propofol caused differences in expression levels of PI3K-AKT signaling pathway genes and it was suggested that these differences may be related to apoptosis induction.

Keywords: Propofol, PI3K-AKT, glioblastoma, gene expression, signaling pathway, apoptosis.

Graphical Abstract

[1]
Louis, D.N.; Perry, A.; Reifenberger, G.; von Deimling, A.; Figarella-Branger, D.; Cavenee, W.K.; Ohgaki, H.; Wiestler, O.D.; Kleihues, P.; Ellison, D.W. The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathol., 2016, 131(6), 803-820.
[http://dx.doi.org/10.1007/s00401-016-1545-1] [PMID: 27157931]
[2]
Omuro, A.; DeAngelis, L.M. Glioblastoma and other malignant gliomas: A clinical review. JAMA, 2013, 310(17), 1842-1850.
[http://dx.doi.org/10.1001/jama.2013.280319] [PMID: 24193082]
[3]
Xu, J.; Xu, W.; Zhu, J. Propofol suppresses proliferation and invasion of glioma cells by upregulating microRNA-218 expression. Mol. Med. Rep., 2015, 12(4), 4815-4820.
[http://dx.doi.org/10.3892/mmr.2015.4014] [PMID: 26133092]
[4]
Li, P.; Guo, P.; Lin, C.; He, M.; Zhu, X.; Liu, C.; Tang, J.; Wang, W.; Liang, W. The synergistic effect of propofol and ulinastatin suppressed the viability of the human lung adenocarcinoma epithelial A549 cell line. Oncol. Lett., 2018, 16(4), 5191-5199. a
[http://dx.doi.org/10.3892/ol.2018.9283 ] [PMID: 30250587]
[5]
Du, Q.; Liu, J.; Zhang, X.; Zhang, X.; Zhu, H.; Wei, M.; Wang, S. Propofol inhibits proliferation, migration, and invasion but promotes apoptosis by regulation of Sox4 in endometrial cancer cells. Braz. J. Med. Biol. Res., 2018, 51(4)e6803
[http://dx.doi.org/10.1590/1414-431x20176803] [PMID: 29490000]
[6]
Liu, S.Q.; Zhang, J.L.; Li, Z.W.; Hu, Z.H.; Liu, Z.; Li, Y. Propofol inhibits proliferation, migration, invasion and promotes apoptosis through down-regulating mir-374a in hepatocarcinoma cell lines. Cell. Physiol. Biochem., 2018, 49(6), 2099-2110.
[http://dx.doi.org/10.1159/000493814] [PMID: 30257238]
[7]
Li, Y.; Dong, W.; Yang, H.; Xiao, G. Propofol suppresses proliferation and metastasis of colorectal cancer cells by regulating miR-124-3p.1/AKT3. Biotechnol. Lett., 2020, 42(3), 493-504.
[http://dx.doi.org/10.1007/s10529-019-02787-y] [PMID: 31894425]
[8]
Zhang, W.; Wang, Y.; Zhu, Z.; Zheng, Y.; Song, B. Propofol inhibits proliferation, migration and invasion of gastric cancer cells by up-regulating microRNA-195. Int. J. Biol. Macromol., 2018, 120(Pt A), 975-984.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.08.173] [PMID: 30171944]
[9]
Li, Q.; Cui, S.; Jing, G.; Ding, H.; Xia, Z.; He, X. The role of PI3K/Akt signal pathway in the protective effects of propofol on intestinal and lung injury induced by intestinal ischemia/reperfusion1. Acta Cir. Bras., 2019, 34(1)e20190010000005
[http://dx.doi.org/10.1590/s0102-865020190010000005] [PMID: 30785506]
[10]
Wei, Q.; Zhao, J.; Zhou, X.; Yu, L.; Liu, Z.; Chang, Y. Propofol can suppress renal ischemia-reperfusion injury through the activation of PI3K/AKT/mTOR signal pathway. Gene, 2019, 708, 14-20.
[http://dx.doi.org/10.1016/j.gene.2019.05.023] [PMID: 31082504]
[11]
Zhang H bin, Tu X kun, Chen Q, Shi S Sheng. Propofol reduces inflammatory brain injury after subarachnoid hemorrhage: Involvement of PI3K/Akt pathway. J. Stroke Cerebrovasc. Dis., 2019.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.104375]
[12]
Lakshmanan, I.; Batra, S.K. Protocol for apoptosis assay by flow cytometry using Annexin V staining method. Bio Protoc., 2013, 3(6)e374
[http://dx.doi.org/10.21769/BioProtoc.374] [PMID: 27430005]
[13]
Cossarizza, A.; Baccarani-Contri, M.; Kalashnikova, G.; Franceschi, C. A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Biochem. Biophys. Res. Commun., 1993, 197(1), 40-45.
[http://dx.doi.org/10.1006/bbrc.1993.2438] [PMID: 8250945]
[14]
Walsh, C.T. Propofol: Milk of Amnesia. Cell, 2018, 175(1), 10-13.
[http://dx.doi.org/10.1016/j.cell.2018.08.031] [PMID: 30217361]
[15]
Marik, P.E. Propofol: therapeutic indications and side-effects. Curr. Pharm. Des., 2004, 10(29), 3639-3649.
[http://dx.doi.org/10.2174/1381612043382846] [PMID: 15579060]
[16]
Jiang, S.; Liu, Y.; Huang, L.; Zhang, F.; Kang, R. Effects of propofol on cancer development and chemotherapy: Potential mechanisms. Eur. J. Pharmacol., 2018, 831, 46-51.
[http://dx.doi.org/10.1016/j.ejphar.2018.04.009] [PMID: 29654781]
[17]
Wei, J.; Jing, L.; Xin, L. How does the anesthetic agent propofol affect tumors? Int. J. Clin. Exp. Med., 2017, 10, 5995-6003.
[18]
Zhang, J.; Wu, G.Q.; Zhang, Y.; Feng, Z.Y.; Zhu, S.M. Propofol induces apoptosis of hepatocellular carcinoma cells by upregulation of microRNA-199a expression. Cell Biol. Int., 2013, 37(3), 227-232.
[http://dx.doi.org/10.1002/cbin.10034] [PMID: 23319430]
[19]
Li, R.; Liu, H.; Dilger, J.P.; Lin, J. Effect of propofol on breast cancer cell, the immune system, and patient outcome. BMC Anesthesiol., 2018, 18(1), 77. [b]
[http://dx.doi.org/10.1186/s12871-018-0543-3] [PMID: 29945542]
[20]
Xu, W.; Zheng, J.; Bie, S.; Kang, L.; Mao, Q.; Liu, W.; Guo, J.; Lu, J.; Xia, R. Propofol inhibits Wnt signaling and exerts anticancer activity in glioma cells. Oncol. Lett., 2018, 16(1), 402-408.
[http://dx.doi.org/10.3892/ol.2018.8606] [PMID: 29928428]
[21]
Chang, F.; Lee, J.T.; Navolanic, P.M.; Steelman, L.S.; Shelton, J.G.; Blalock, W.L.; Franklin, R.A.; McCubrey, J.A. Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy. Leukemia, 2003, 17(3), 590-603.
[http://dx.doi.org/10.1038/sj.leu.2402824] [PMID: 12646949]
[22]
Farhan, M.; Wang, H.; Gaur, U.; Little, P.J.; Xu, J.; Zheng, W. FOXO signaling pathways as therapeutic targets in cancer. Int. J. Biol. Sci., 2017, 13(7), 815-827.
[http://dx.doi.org/10.7150/ijbs.20052] [PMID: 28808415]
[23]
Brown, A.K.; Webb, A.E. Regulation of foxo factors in mammalian cells. Curr. Top. Dev. Biol., 2018, 127, 165-192.
[http://dx.doi.org/10.1016/bs.ctdb.2017.10.006] [PMID: 29433737]
[24]
Yoshino, Y.; Ishioka, C. Inhibition of glycogen synthase kinase-3 beta induces apoptosis and mitotic catastrophe by disrupting centrosome regulation in cancer cells. Sci. Rep., 2015, 5, 13249.
[http://dx.doi.org/10.1038/srep13249] [PMID: 26292722]
[25]
Garcia-Ortega, M.B.; Lopez, G.J.; Jimenez, G.; Garcia-Garcia, J.A.; Conde, V.; Boulaiz, H.; Carrillo, E.; Perán, M.; Marchal, J.A.; Garcia, M.A. Clinical and therapeutic potential of protein kinase PKR in cancer and metabolism. Expert Rev. Mol. Med., 2017, 19e9
[http://dx.doi.org/10.1017/erm.2017.11] [PMID: 28724458]
[26]
Liu, Z.G.; Jiang, G.; Tang, J.; Wang, H.; Feng, G.; Chen, F.; Tu, Z.; Liu, G.; Zhao, Y.; Peng, M.J.; He, Z.W.; Chen, X.Y.; Lindsay, H.; Xia, Y.F.; Li, X.N. c-Fos over-expression promotes radioresistance and predicts poor prognosis in malignant glioma. Oncotarget, 2016, 7(40), 65946-65956.
[http://dx.doi.org/10.18632/oncotarget.11779] [PMID: 27602752]
[27]
Debinski, W.; Gibo, D.M. Fos-related antigen 1 modulates malignant features of glioma cells. Mol. Cancer Res., 2005, 3(4), 237-249.
[http://dx.doi.org/10.1158/1541-7786.MCR-05-0004] [PMID: 15831677]
[28]
Li, D.; Chi, G.; Chen, Z.; Jin, X. MicroRNA-1225-5p behaves as a tumor suppressor in human glioblastoma via targeting of IRS1. OncoTargets Ther., 2018, 11, 6339-6350.
[http://dx.doi.org/10.2147/OTT.S178001] [PMID: 30319274]
[29]
Sun, Q.; Zhou, C.; Ma, R.; Guo, Q.; Huang, H.; Hao, J.; Liu, H.; Shi, R.; Liu, B. Prognostic value of increased integrin-beta 1 expression in solid cancers: a meta-analysis. OncoTargets Ther., 2018, 11, 1787-1799.
[http://dx.doi.org/10.2147/OTT.S155279] [PMID: 29636624]
[30]
PI3K-Akt signaling pathway of Kanehisa Laboratories 04151. vailable from: https://www.genome.jp/kegg-bin/show_pathway?hsa04151+3688 [Accessed 25 May 2020]
[31]
Fang, B.; Li, G.; Xu, C.; Hui, Y.; Li, G. MicroRNA miR-1249 downregulates adenomatous polyposis coli 2 expression and promotes glioma cells proliferation. Am. J. Transl. Res., 2018, 10(5), 1324-1336.
[PMID: 29887948]
[32]
Wang, Z.; Cao, B.; Ji, P.; Yao, F. Propofol inhibits tumor angiogenesis through targeting VEGF/VEGFR and mTOR/eIF4E signaling. Biochem. Biophys. Res. Commun., 2021, 555, 13-18.
[http://dx.doi.org/10.1016/j.bbrc.2021.03.094] [PMID: 33812053]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy