Comparison of the Effect of S14161 Small Molecule and Glaucium Flavum Extract on A549 Cancer Cells
DOI:
https://doi.org/10.31661/gmj.v10i.2151Keywords:
Lung Cancer, Glaucium Flavum, S14161 Small Molecule, Apoptosis, Gene ExpressionAbstract
Background: Lung cancer is the fifth most common cancer in Iran. Due to the side effects of common cancer treatments, everyone has turned to herbal remedies and new treatments. This study aimed to compare the effect of S14161 small molecule and Glaucium flavum extract on the induction of apoptosis in A549 cancer cells. Materials and Methods: In this study, the A549 cell line was treated with different concentrations of S14161 small molecule and G. flavum extract compounds. MTT assay was performed to determine the half-maximal inhibitory concentration (IC50) and compare the viability of treated cells on days 1, 3, and 5. Also, the real-time polymerase chain reaction assay was used to investigate the expressions of pro- and anti-apoptotic genes. Results: MTT results showed that both the combination of S14161 and G. flavum extract resulted in cell death and reduced cancer cell viability. However, the viability rate was greater by S14161, and this small molecule significantly increased the expression of Bax, P53, and Bad apoptotic genes and decreased the expression of the Bcl2 gene, which shows the induced apoptotic effect of S14161 in comparison with G. flavum. Conclusion: The results of this study showed that S14161 had fewer IC50 and caused cell death by inhibiting the PI3K/AKT pathway, and Glaucium flavum caused cancer cell death due to its alkaloid compounds. Therefore, both compounds are recommended as drug candidates for the treatment of lung cancer.
[GMJ.2021;10:e2151]
References
Munson L, Moresco A. Comparative pathology of mammary gland cancers in domestic and wild animals. Breast Dis. 2007;28(1):7-21. https://doi.org/10.3233/BD-2007-28102PMid:18057539 Lam WK. Lung cancer in Asian women-the environment and genes. Respirology. 2005;10(4):408-17. https://doi.org/10.1111/j.1440-1843.2005.00723.xPMid:16135162 Janku F, Stewart DJ, Kurzrock R. Targeted therapy in non-small-cell lung cancer-is it becoming a reality? Nat Rev Clin Oncol. 2010;7(7):401-14. https://doi.org/10.1038/nrclinonc.2010.64PMid:20551945 Zhao Y, Bao Q, Renner A, Camaj P, Eichhorn M, Ischenko I et al. Cancer stem cells and angiogenesis. Int J Dev Biol. 2011;55(4-5):477-82. https://doi.org/10.1387/ijdb.103225yzPMid:21732274 Mohamadi T, Hoveizi E. Comparison of anti proliferative effect of cinnamon (Cinnamomum zeylanicum) hydroalcoholic extract with cyclophosphamide medicine on A459 Cancer Cells. Razi Journal of Medical Sciences. 2018;25(167). Torkiâ€Boldaji B, Tavalaee M, Bahadorani M, Nasrâ€Esfahani M. Selection of physiological spermatozoa during intracytoplasmic sperm injection. Andrologia. 2017;49(1):e12579. https://doi.org/10.1111/and.12579PMid:27037571 Cheraghi J, Krishchi P, Nasri S, Boorboor M. 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;23:190-202. Darya GH, Nowroozi-Asl A, Khoshvaghti A, Musavi SM. Effect of hydro-alcoholic extract of yellow horned poppy (Glaucium flavum) on serum concentration of glucose and lipid profile and weight changes in alloxan induced diabetic rats. Scientific Journal of Kurdistan University of Medical Sciences. 2019;24(1):45-55. https://doi.org/10.29252/sjku.24.1.45 Bogdanov MG, Svinyarov I, Keremedchieva R, Sidjimov A. Ionic liquid-supported solid-liquid extraction of bioactive alkaloids. I. New HPLC method for quantitative determination of glaucine in Glaucium flavum Cr.(Papaveraceae). Separation and purification technology. 2012;97:221-7. https://doi.org/10.1016/j.seppur.2012.02.001 Cortijo J, Villagrasa V, Pons R, Berto L, MartÃâ€Cabrera M, Martinezâ€Losa M et al. Bronchodilator and antiâ€inflammatory activities of glaucine: In vitro studies in human airway smooth muscle and polymorphonuclear leukocytes. Br J Pharmacol. 1999;127(7):1641-51. https://doi.org/10.1038/sj.bjp.0702702PMid:10455321 PMCid:PMC1566148 Chang M-C, Chan C-P, Wang Y-J, Lee P-H, Chen L-I, Tsai Y-L et al. Induction of necrosis and apoptosis to KB cancer cells by sanguinarine is associated with reactive oxygen species production and mitochondrial membrane depolarization. Toxicol Appl Pharmacol. 2007;218(2):143-51. https://doi.org/10.1016/j.taap.2006.10.025PMid:17196629 Spasova M, Philipov S, Nikolaeva-Glomb L, Galabov A, Milkova T. Cinnamoyl-and hydroxycinnamoyl amides of glaucine and their antioxidative and antiviral activities. Bioorg Med Chem. 2008;16(15):7457-61. https://doi.org/10.1016/j.bmc.2008.06.010PMid:18590964 Boulaaba M, Kalai FZ, Dakhlaoui S, Ezzine Y, Selmi S, Bourgou S et al. Antioxidant, antiproliferative and anti-inflammatory effects of Glaucium Flavum fractions enriched in phenolic compounds. Medicinal Chemistry Research. 2019;28(11):1995-2001. https://doi.org/10.1007/s00044-019-02429-y Haghighi F, Matin MM, Bahrami AR, Iranshahi M, Rassouli FB, Haghighitalab A. The cytotoxic activities of 7-isopentenyloxycoumarin on 5637 cells via induction of apoptosis and cell cycle arrest in G2/M stage. Daru. 2014;22(1):1-10. https://doi.org/10.1186/2008-2231-22-3PMid:24393601 PMCid:PMC3898598 Thakur A, Singla R, Jaitak V. Coumarins as anticancer agents: A review on synthetic strategies, mechanism of action and SAR studies. Eur J Med Chem. 2015;101:476-95. https://doi.org/10.1016/j.ejmech.2015.07.010PMid:26188907 Mao X, Cao B, Wood TE, Hurren R, Tong J, Wang X et al. A small-molecule inhibitor of D-cyclin transactivation displays preclinical efficacy in myeloma and leukemia via phosphoinositide 3-kinase pathway. Blood. 2011;117(6):1986-97. https://doi.org/10.1182/blood-2010-05-284810PMid:21135258 Sandhu S, Bansal Y, Silakari O, Bansal G. Coumarin hybrids as novel therapeutic agents. Bioorg Med Chem. 2014;22(15):3806-14. https://doi.org/10.1016/j.bmc.2014.05.032PMid:24934993 Carvalho AA, Andrade LN, de Sousa ÉBV, de Sousa DP. Antitumor phenylpropanoids found in essential oils. Biomed Res Int. 2015;2015:392674. https://doi.org/10.1155/2015/392674PMid:25949996 PMCid:PMC4408748 Meimandi K, Yaghoobi M. Effects of aqueous and ethanolic extract of Rosa damascena Mill L. against human gastric cancer cells. 2015. HAJI AF, Ostad S, Khanavi M, HAJI AA, Farahanikia B, Salarytabar A. Cytotoxicity of two species of Glaucium from Iran. 2013. Kuo H-P, Chuang T-C, Tsai S-C, Tseng H-H, Hsu S-C, Chen Y-C et al. Berberine, an isoquinoline alkaloid, inhibits the metastatic potential of breast cancer cells via Akt pathway modulation. J Agric Food Chem. 2012;60(38):9649-58. https://doi.org/10.1021/jf302832nPMid:22950834 Hijazi MA, Aboul-Ela M, Bouhadir K, Fatfat M, Khalife H, Ellakany A et al. Cytotoxic Activity of Alkaloids from Papaver rhoeas growing in Lebanon. Rec Nat Prod. 2017;11:211-6. Ahmad N, Gupta S, Husain MM, Heiskanen KM, Mukhtar H. Differential antiproliferative and apoptotic response of sanguinarine for cancer cells versus normal cells. Clin Cancer Res. 2000;6(4):1524-8. Chmura SJ, Dolan ME, Cha A, Mauceri HJ, Kufe DW, Weichselbaum RR. In vitro and in vivo activity of protein kinase C inhibitor chelerythrine chloride induces tumor cell toxicity and growth delay in vivo. Clin Cancer Res. 2000;6(2):737-42. Williams GH, Stoeber K. The cell cycle and cancer. J Pathol. 2012;226(2):352-64. https://doi.org/10.1002/path.3022PMid:21990031 Chen C-H, Liao C-H, Chang Y-L, Guh J-H, Pan S-L, Teng C-M. Protopine, a novel microtubule-stabilizing agent, causes mitotic arrest and apoptotic cell death in human hormone-refractory prostate cancer cell lines. Cancer Lett. 2012;315(1):1-11. https://doi.org/10.1016/j.canlet.2011.09.042PMid:22033245 Bournine L, Bensalem S, Peixoto P, Gonzalez A, Maiza-Benabdesselam F, Bedjou F et al. Revealing the anti-tumoral effect of Algerian Glaucium flavum roots against human cancer cells. Phytomedicine. 2013;20(13):1211-8. https://doi.org/10.1016/j.phymed.2013.06.007PMid:23860409 Ulusoy S, BoÅŸgelmez-Tınaz G, SeçilmiÅŸ-Canbay H. Tocopherol, carotene, phenolic contents and antibacterial properties of rose essential oil, hydrosol and absolute. Curr Microbiol. 2009;59(5):554-8. https://doi.org/10.1007/s00284-009-9475-yPMid:19688375 Sarfaraz S, Afaq F, Adhami VM, Malik A, Mukhtar H. Cannabinoid receptor agonist-induced apoptosis of human prostate cancer cells LNCaP proceeds through sustained activation of ERK1/2 leading to G1 cell cycle arrest. J Biol Chem. 2006;281(51):39480-91. https://doi.org/10.1074/jbc.M603495200PMid:17068343 Ely S, Di Liberto M, Niesvizky R, Baughn LB, Cho HJ, Hatada EN et al. Mutually exclusive cyclin-dependent kinase 4/cyclin D1 and cyclin-dependent kinase 6/cyclin D2 pairing inactivates retinoblastoma protein and promotes cell cycle dysregulation in multiple myeloma. Cancer Res. 2005;65(24):11345-53. https://doi.org/10.1158/0008-5472.CAN-05-2159PMid:16357141 Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT. The PI3K pathway in human disease. Cell. 2017;170(4):605-35. https://doi.org/10.1016/j.cell.2017.07.029PMid:28802037 PMCid:PMC5726441 Han K, Xu X, Chen G, Zeng Y, Zhu J, Du X et al. Identification of a promising PI3K inhibitor for the treatment of multiple myeloma through the structural optimization. J Hematol Oncol. 2014;7(1):1-13. https://doi.org/10.1186/1756-8722-7-9PMid:24428908 PMCid:PMC3924225 Tian H, Zhang Y, Zhang Q, Li S, Liu Y, Han X. Effects of BENC-511, a novel PI3K inhibitor, on the proliferation and apoptosis of A549 human lung adenocarcinoma cells. Biosci Trends. 2019;13(1):40-8. https://doi.org/10.5582/bst.2019.01006PMid:30867372 Wang Q, Guo Y, Jiang S, Dong M, Kuerban K, Li J et al. A hybrid of coumarin and phenylsulfonylfuroxan induces caspase-dependent apoptosis and cytoprotective autophagy in lung adenocarcinoma cells. Phytomedicine. 2018;39:160-7. https://doi.org/10.1016/j.phymed.2017.12.029PMid:29433677 Mao C, Patterson NM, Cherian MT, Aninye IO, Zhang C, Montoya JB et al. A new small molecule inhibitor of estrogen receptor α binding to estrogen response elements blocks estrogen-dependent growth of cancer cells. J Biol Chem. 2008;283(19):12819-30. https://doi.org/10.1074/jbc.M709936200PMid:18337247 PMCid:PMC2442351 Harris T. PDK1 and PKB/Akt: ideal targets for development of new strategies to structureâ€based drug design. IUBMB life. 2003;55(3):117-26. https://doi.org/10.1080/1521654031000115951PMid:12822887
