Antitumor Effect of the Chalcone Analogue, (E) -1-(4-Ethoxy-3-Methoxyphenyl) -5- Methylhex-1-En-3-One on HeLa Cell Line

Lukovic, Jovan; Mitrovic, Marina; Zelen, Ivanka; Čanovic, Petar; Zaric, Milan; Nikolic, Ivana

doi:10.2478/sjecr-2018-0048

Abstract

Chalcones represent precursor compounds for flavonoids biosynthesis in plants. Chalcones, 1,3-diaryl-2-propen-1-ones, have unique chemical structure with conjugated double bonds and delocalized π-electron system on both aromatic rings. Various studies have shown that chemical structure of chalcone is responsible for their antitumor effect. In our study, we have examined the antitumor effect of chalcone analogue (E) -1- (4-ethoxy-3-methoxyphenyl) -5-methylhex-1-en-3-one (CH) on HeLa cells. The antitumor efficiency of different CH concentrations was compared to the antitumor effects of dehydrozingerone and cisplatin. The viability of the cells was evaluated using MTT assay; type of the cell death was evaluated by Annexin V-FITC/7-AAD staining using FACS analysis; morphology changes of treated cells were visualized and compared to untreated cells using phase contrast microscopy. The result of our research showed that CH have a stronger antitumor compared to the effect both of dehydrozingerone and cisplatin. Our results indicated that chalcone analogue induced cell death via activation of apoptosis more powerfully compared to the apoptosis induced with dehydrozingerone and cisplatin.

References

1. Abdelwahab, S. I., Abdul, A. B., Zain, Z. N. M., & Hadi, A. H. A. (2012) Zerumbone inhibits interleukin-6 and induces apoptosis and cell cycle arrest in ovarian and cervical cancer cells International Immunopharmacology 12(4):594–602. https://doi.org/10.1016/j.intimp.2012.01.01410.1016/j.intimp.2012.01.01422330084
Search in Google Scholar Back to article
2. Ahmed, F. F., Abd El-Hafeez, A. A., Abbas, S. H., Abdelhamid, D., & Abdel-Aziz, M. (2018) New 1,2,4-triazole-Chalcone hybrids induce Caspase-3 dependent apoptosis in A549 human lung adenocarcinoma cells European Journal of Medicinal Chemistry 151:705–722. https://doi.org/10.1016/j.ejmech.2018.03.07310.1016/j.ejmech.2018.03.07329660690
Open DOI Search in Google Scholar Back to article
3. Alibeiki, F., Jafari, N., Karimi, M., & Peeri Dogaheh, H. (2017) Potent anti-cancer effects of less polar Curcumin analogues on gastric adenocarcinoma and esophageal squamous cell carcinoma cells Scientific Reports 7(1):1–9. https://doi.org/10.1038/s41598-017-02666-410.1038/s41598-017-02666-4545138628566729
Open DOI Search in Google Scholar Back to article
4. An, B., Zhang, S., Yan, J., Huang, L., & Li, X. (2017) Synthesis, in vitro and in vivo evaluation of new hybrids of millepachine and phenstatin as potent tubulin polymerization inhibitors Organic and Biomolecular Chemistry 15(4):852–862. https://doi.org/10.1039/C6OB02507B10.1039/602507
Open DOI Search in Google Scholar Back to article
5. Ball, C., & Madden, J. E. (2003) Update on cervical cancer screening: Current diagnostic and evidence-based management protocols Postgraduate Medicine 113(2):59–70. https://doi.org/10.3810/pgm.2003.02.137510.3810/pgm.2003.02.137512611115
Open DOI Search in Google Scholar Back to article
6. Burmudžija, A. Z., Muškinja, J. M., Kosanić, M. M., Ranković, B. R., Novaković, S. B., Đorđević, S. B., … Ratković, Z. R. (2017) Cytotoxic and Antimicrobial Activity of Dehydrozingerone based Cyclopropyl Derivatives Chemistry and Biodiversity 14(8). https://doi.org/10.1002/cbdv.20170007710.1002/cbdv.20170007728388815
Search in Google Scholar Back to article
7. Fogaça, T. B., Martins, R. M., Begnini, K. R., Carapina, C., Ritter, M., de Pereira, C. M. P., … Collares, T. (2017) Apoptotic effect of chalcone derivatives of 2-acetylthiophene in human breast cancer cells Pharmacological Reports 69(1):156–161. https://doi.org/10.1016/j.pharep.2016.10.00310.1016/j.pharep.2016.10.00327923159
Open DOI Search in Google Scholar Back to article
8. Gao, S., Sun, D., Wang, G., Zhang, J., Jiang, Y., Li, G., … Chen, L. (2016) Growth inhibitory effect of paratocarpin E, a prenylated chalcone isolated from Euphorbia humifusa Wild., by induction of autophagy and apoptosis in human breast cancer cells Bioorganic Chemistry 69:121–128. https://doi.org/10.1016/j.bioorg.2016.10.00510.1016/j.bioorg.2016.10.00527814565
Search in Google Scholar Back to article
9. K. Sahu, N., S. Balbhadra, S., Choudhary, J., & V. Kohli, D. (2012) Exploring Pharmacological Significance of Chalcone Scaffold: A Review Current Medicinal Chemistry 19(2):209–225. https://doi.org/10.2174/09298671280341413210.2174/09298671280341413222320299
Open DOI Search in Google Scholar Back to article
10. Kim, M. J., Kadayat, T., Um, Y. J., Jeong, T. C., Lee, E. S., & Park, P. H. (2015) Inhibitory effect of 3-(4-hydroxyphenyl)-1-(thiophen-2-yl) prop-2-en-1-one, a chalcone derivative on MCP-1 expression in macrophages via inhibition of ROS and Akt signaling Biomolecules and Therapeutics 23(2):119–127. https://doi.org/10.4062/biomolther.2014.12710.4062/biomolther.2014.127435431225767679
Search in Google Scholar Back to article
11. Kolundžija, B., Marković, V., Stanojković, T., Joksović, L., Matić, I., Todorović, N., … Joksović, M. D. (2014) Novel anthraquinone based chalcone analogues containing an imine fragment: Synthesis, cytotoxicity and anti-angiogenic activity Bioorganic and Medicinal Chemistry Letters 24(1):546–548. https://doi.org/10.1016/j.bmcl.2013.11.07510.1016/j.bmcl.2013.11.07524332490
Open DOI Search in Google Scholar Back to article
12. Kubra, I. R., Bettadaiah, B. K., Murthy, P. S., & Rao, L. J. M. (2014) Structure-function activity of dehydrozingerone and its derivatives as antioxidant and antimicrobial compounds Journal of Food Science and Technology 51(2):245–255. https://doi.org/10.1007/s13197-011-0488-810.1007/s13197-011-0488-8390764824493881
Open DOI Search in Google Scholar Back to article
13. Kuo, P.-C., Damu, A. G., Cherng, C.-Y., Jeng, J.-F., Teng, C.-M., Lee, E.-J., & Wu, T.-S. (2005) Isolation of a natural antioxidant, dehydrozingerone from Zingiber officinale and synthesis of its analogues for recognition of effective antioxidant and antityrosinase agents. Archives of Pharmacal Research 28(5):518–528.10.1007/BF0297775215974436
Open DOI Search in Google Scholar Back to article
14. Lahsasni, S., Al Korbi, F., & Aljaber, N. A.-A. (2014) Synthesis, characterization and evaluation of antioxidant activities of some novel chalcones analogues Chemistry Central Journal 8(1):32. https://doi.org/10.1186/1752-153X-8-3210.1186/1752-153X-8-32402682724883080
Open DOI Search in Google Scholar Back to article
15. Li, X., Bau, T., & Bao, H. (2018) FPOA induces apoptosis in HeLa human cervical cancer cells through a caspase-mediated pathway Oncology Letters 8357–8362. https://doi.org/10.3892/ol.2018.838010.3892/ol.2018.8380595002629805569
Open DOI Search in Google Scholar Back to article
16. Mahapatra, D. K., Bharti, S. K., & Asati, V. (2015) Anti-cancer chalcones: Structural and molecular target perspectives European Journal of Medicinal Chemistry 98:69–114. https://doi.org/10.1016/j.ejmech.2015.05.00410.1016/j.ejmech.2015.05.00426005917
Open DOI Search in Google Scholar Back to article
17. Malhotra, J. D., & Kaufman, R. J. (2009) The Endoplasmic Reticulum and the Unfolded Protein Response Semin Cell Dev Biol 18(6):716–731. https://doi.org/10.1016/j.semcdb.2007.09.003.The10.1016/j.semcdb.2007.09.003.
Open DOI Search in Google Scholar Back to article
18. Muñoz, N., Bosch, X., de Sanjosé, S., Herrero, R., Castellsagué, X., Shah, K. V, … Meijer, C. J. L. M. (2003) Epidemiologic classification of human papilloma-virus types associated with cervical cancer N Engl J Med 348(6):518–527. https://doi.org/10.1056/NEJMoa02164110.1056/NEJMoa02164112571259
Open DOI Search in Google Scholar Back to article
19. Muškinja, J., Ratkovi, Z., Rankovi, B., & Kosani, M. (2016) Synthesis of O-Alkyl Derivatives of Dehydrozingerone Analogues Kragujevac Journal Science 38:97–106.10.5937/KgJSci1638097M
Search in Google Scholar Back to article
20. Naumovic, T., Miljus, D., Djoric, M., Zivkovic, S., & Perisic, Z. (2015) Mortality from cervical cancer in Serbia in the period 1991-2011 Journal of B.U.ON. 20(1):231–234.
Search in Google Scholar Back to article
21. Norbury, C. J., & Hickson, I. D. (2001) C r dna d367–401.10.1146/annurev.pharmtox.41.1.36711264462
Search in Google Scholar Back to article
22. Ramirez-Tagle, R., Escobar, C. A., Romero, V., Montorfano, I., Armisén, R., Borgna, V., … Echeverria, C. (2016) Chalcone-induced apoptosis through caspase-dependent intrinsic pathways in human hepatocellular carcinoma cells International Journal of Molecular Sciences 17(2). https://doi.org/10.3390/ijms1702026010.3390/ijms17020260
Open DOI Search in Google Scholar Back to article
23. Taguchi, T., Nazneen, A., Abid, M. R., & Razzaque, M. S. (2005) Cisplatin-Associated Nephrotoxicity and Pathological Events In Cellular Stress Responses in Renal Diseases (pp. 107–121). https://doi.org/10.1159/00008605510.1159/000086055
Open DOI Search in Google Scholar Back to article
24. Takac, P., Kello, M., Pilatova, M. B., Kudlickova, Z., Vilkova, M., Slepcikova, P., … Mojzis, J. (2018) New chalcone derivative exhibits antiproliferative potential by inducing G2/M cell cycle arrest, mitochondrial-mediated apoptosis and modulation of MAPK signalling pathway Chemico-Biological Interactions 292(July):37–49. https://doi.org/10.1016/j.cbi.2018.07.00510.1016/j.cbi.2018.07.005
Open DOI Search in Google Scholar Back to article
25. Tamm, I., Schriever, F., & Dörken, B. (2001) Apoptosis: implications of basic research for clinical oncology. The Lancet Oncology 2(1):33–42. https://doi.org/10.1016/S1470-2045(00)00193-510.1016/S1470-2045(00)00193-5
Open DOI Search in Google Scholar Back to article
26. Wu, W., Liu, Y., & Zhu, D. (2010) π-Conjugated molecules with fused rings for organic field-effect transistors: Design, synthesis and applications Chemical Society Reviews 39(5):1489–1502. https://doi.org/10.1039/b813123f10.1039/B813123F20419204
Open DOI Search in Google Scholar Back to article
27. Zhang, B., Duan, D., Ge, C., Yao, J., Liu, Y., Li, X., & Fang, J. (2015) Synthesis of xanthohumol analogues and discovery of potent thioredoxin reductase inhibitor as potential anticancer agent Journal of Medicinal Chemistry 58(4):1795–1805. https://doi.org/10.1021/jm501650710.1021/jm501650725629304
Open DOI Search in Google Scholar Back to article
28. Zhao, L., Mao, L., Hong, G., Yang, X., & Liu, T. (2015) Design, synthesis and anticancer activity of matrine-1H-1,2,3-triazole-chalcone conjugates Bioorganic and Medicinal Chemistry Letters 25(12):2540–2544. https://doi.org/10.1016/j.bmcl.2015.04.05110.1016/j.bmcl.2015.04.05125959813
Open DOI Search in Google Scholar Back to article
29. Zhao, S., Ma, C.-M., Liu, C.-X., Wei, W., Sun, Y., Yan, H., & Wu, Y.-L. (2012) Autophagy inhibition enhances isobavachalcone-induced cell death in multiple myeloma cells. International Journal of Molecular Medicine 30(4):939–944. https://doi.org/10.3892/ijmm.2012.1066.10.3892/ijmm.2012.106622824846
Open DOI Search in Google Scholar Back to article

Antitumor Effect of the Chalcone Analogue, (E) -1-(4-Ethoxy-3-Methoxyphenyl) -5- Methylhex-1-En-3-One on HeLa Cell Line

Abstract

Paradigm

My account