The effect of GW9508 on cytotoxicity and gene expression of P53 in C118 cell line
Archives of Advances in Biosciences,
Vol. 12 No. 3 (2021),
10 July 2021
,
Page 41-54
https://doi.org/10.22037/aab.v12i3.35012
Abstract
Introduction: As one of the most common and invasive brain tumors, glioblastoma which originates in the nervous tissue of the brain has remained a therapeutic challenge given low success of conventional therapies. Small molecules including GW9508, due to their different roles in signaling and intracellular pathways and the production and increase of oxidative stress of mitochondrial origin, can cause cells to progress to apoptosis, also known as a cost-effective pharmacological factor. Therefore, in the present study, the anticancer and cytotoxic effects of GW9508 on A549 class lung cancer cells were investigated.
Materials and Methods: In this experiment, the cell line (C118) was firstly cultured in DMEM culture medium containing 10% FBS and then treated with different concentrations of GW9508. MTT assay was used to determine IC50 and compare the viability of treated cells with different concentrations of GW9508 on days 1, 3, and 5 in the control group. To evaluate the effect, the qRT-PCR test was used with the IC50 concentration on the induction of apoptosis and expression of the P53 gene.
Results: The results showed that GW9508 significantly reduced the viability and proliferation of C118 cells in a dose- and time-dependent manner (P <.05). Morphological changes such as reduction of chromatin density and cell rotation were also observed in the cells. Also, molecular results showed that GW9508 was able to increase the expression of the P53 gene.
Conclusions: The GW9508 small molecule induces cell death in glioblastoma cancer cells by reducing cell viability and increasing P53 gene expression. As a result, it has therapeutic potential to induce cell death in cancer cells and to treat cancer.
- GW9508 Lung cancer, Apoptosis
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References
2. Movafagh A, Heidari MH, Abdoljabbari M, Mansouri N, Taghavi A, Karamatinia A, Mehrvar N, Hashemi M, Ghazi M. Spiritual Therapy in Coping with Cancer as a Complementary Medical Preventive Practice. J Cancer Prev. 2017 Jun;22(2):82-88
3. Galan-Moya, EM., Le Guelte, A., Lima Fernandes, E., Thirant, C., Dwyer, J., Bidere, N. ,. Secreted factors from brain endothelial cells maintain glioblastoma stem-like cell expansion through the mTOR pathway. Embo Rep; 2011. 12(5):470-6.
4. Dimov, I., Tasic, D., Stefanovic, I., Dimov, D,. New insights into molecular basis of glioblastoma multiforme and associated immunosuppression. Acta Fac Med Naiss 2013. 30(4): 165-84.
5. Chen, J., McKay, R.M., and Parada, L.F., Malignant glioma: lessons from genomics, mouse models, and stem cells. Cell, 2012. 149(1): p. 36-47.
6. Plesan, D., Valentina, G., Patrana, N., Plesan, C., and Stoica, D., Immunohistochemical study of p53 and Ki67 in a group of patients with mammary carcinoma. Rom J Morpho Embryol, 2010. 51 (3): 459–465.
7. Alizadeh, L., and et al. Immunotherapy of Glioblastoma Multiforme Tumors: From Basic to Clinical Trial Studies. The Neuroscience Journal of Shefaye Khatam 3.2 . 2015. 77-84.
8. 8.cheraghi, javad. , et al. The Effect of Ethanolic Extracts of Petroselinum crispum Leaves on Histopathological and Activity of Liver Enzymes in Streptozotocin-Induced Diabetic Rats. scientific journal of ilam university of medical sciences . 2016. 23.7 ;190-202.
9. Borowiak, M., et al., Small molecules efficiently direct endodermal differentiation of mouse and human embryonic stem cells. Cell stem cell. 2009. 4(4): p. 348-358.
10. Fesik, S.W., Promoting apoptosis as a strategy for cancer drug discovery. Nature Reviews Cancer, 2005. 5(11), p.876.
11. Philippe, C., Wauquier, F., Léotoing, L., Coxam, V. and Wittrant, Y., GW9508, a free fatty acid receptor agonist, specifically induces cell death in bone resorbing precursor cells
through increased oxidative stress from mitochondrial origin. Experimental cell research, 2015. 319(19), pp.3035-3041.
12. Gao, B., Huang, Q., Jie, Q., Wang, L., Zhang, H.Y., Liu, J., Yang, L. and Luo, Z.J.,. Dose-response estrogen promotes osteogenic differentiation via GPR40 (FFAR1) in murine BMMSCs. Biochimie, 2015. 110, pp.36-44.
13. Philippe, C., Wauquier, F., Léotoing, L., Coxam, V. and Wittrant, Y., GW9508, a free fatty acid receptor agonist, specifically induces cell death in bone resorbing precursor cells through increased oxidative stress from mitochondrial origin. Experimental cell research, 2013. 319(19), pp.3035-3041.
14. Maher, EA., Furnari, FB., Bachoo, RM., Rowitch, DH., Louis, DN., Cavenee, WK., et al. Malignant glioma: genetics and biology of a grave matter. Genes Dev , 2001. 15(11):1311–33.
15. Omuro, A., DeAngelis, LM., Glioblastoma and other malignant gliomas: A clinical review. JAMA 2013. 310(17):1842-50.
16. Fukushima, K., Yamasaki, E. , Ishii, S., Tomimatsu, A. , and Takahashi, K,. Biochemical and Biophysical Research Communications Different roles of GPR120 and GPR40 in the acquisition of malignant properties in pancreatic cancer cells. Biochemical and Biophysical Research Communications 2015. 8–11.
17. Wu, j,. Inhibition of GPR40 protects MIN6 beta cells from palmitate –induced ER Stress and apoptosis.,J. Cell Bichem 2012. 113(4)1152-1158.
18. Doll, R,. and Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. JNCI: Journal of the National Cancer Institute 1981, 66 (6), 1192–1308.
19. Pierre, A., Minville-walz, M ., Fèvre, C., Hichami, A ., Gresti, J ., Pichon, L,. Biochimica et Biophysica Acta Trans-10 , cis-12 conjugated linoleic acid induced cell death in human colon cancer cells through reactive oxygen species-mediated ER stress. BBA - Molecular and Cell Biology of Lipids, 2013. 1831 (4), 759–768.
20. Hardman , W.E., ω-3 Fatty acids to augment cancer therapy. J. Nutr 2002. 132, 3509S–3512S.
21. Zheng, J.S., Hu, X.J., Zao, Y.M., Yang, J., Li D. Intake of fish and marine n-3 polyunsaturated fatty acids and risk of breast cancer: Meta-analysis of data from 21 Independent Prospective Cohort Studies. Br. Med. J. 2013. 346, f3706. [CrossRef] [PubMed]
22. Lin, DC., Guo , Q., Luo , J. , Zhang, J., Nguyen, K., Chen, M., et al. Identification and pharmacological characterization of multiple allosteric binding sites on the free fatty acid 1 receptor. Molecular Pharmacology 2012. 82; 843–859.
23. Hopkins, M. M., Zhang, Z ., Liu, Z. , & Meier, K. E,. Eicosopentaneoic acid and other free fatty acid receptor agonists inhibit lysophosphatidic acid-and epidermal growth factor-induced proliferation of human breast cancer cells. Journal of clinical medicine 2016. 5(2), 16. 24. Gao, B ., Huang, Q ., Jie, Q. , Wang, L ., Zhang , H.Y ., Liu, J. , Yang, L,. and Luo, Z.J. Dose-response estrogen promotes osteogenic differentiation via GPR40 (FFAR1) in murine BMMSCs. Biochimie 2015. 110, pp.36-44.
25. Honardoost, M ., Soleimanjahi , H., and Rajaei, F,. Apoptosis: programmed cell death .Journal of Qazvin University of Medical Science 2013.
26. Rafienia, B., Hoveizi, E., and Shahriari, A., Apoptotic effect of GW9508 small molecule on HT29 cancer cells in the fibrin hydrogel scaffold, in. 2018.
27. Kroemer, G,. Mitochondrial control of apoptosis: an introduction. Biochemical and Biophysical Research Communications 2003. 304 (3), 433–435.
28. Oroz-Parra, I., Apoptosis activation in human lung cancer cell lines by a novel synthetic peptide derived from Conus californicus venom. Toxins, 2016. ( Basel ). , vol. 8, no. 2.
29. Rahko, E., Blanco, G., Soini, Y., Bloigu, R. and Jukkola, A., A mutant TP53 gene status is associated with a poor prognosis and anthracycline-resistance in breast cancer patients. Eur J Canc, 2003. 39: 447–453.
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