Original Article

Anticancer Properties of Fluorinated Aminophenylhydrazines on A549 Lung Carcinoma Cell Line

Abstract

Background: Non-small cell lung cancer (NSCLC) is responsible for up to 85% of deaths associated with lung cancer. Chemotherapy is still an important treatment method on the treatment of inoperable cases. In this study, the anticancer properties of a series of Schiff bases were tested on the A549 cell line representing NSCLC.

Methods: Fluorinated Schiff bases (compounds 1-6) were synthesized based on 2-amino phenylhydrazines and benzaldehydes containing fluorine were used. The cytotoxic effects of the compounds on the A549 cell line were determined by colorimetric MTT assay and the antiproliferative effects of the compounds on the A549 cell line by the CFSE method. To demonstrate the development of apoptosis, cleaved caspase-3 expression in cells was tested using the immunofluorescence method. Morphological changes indicating apoptosis in cells were determined by histopathological staining methods (H & E, giemza, PAP).

Results: The strongest cytotoxic effect on A549 lung cancer cells was obtained with compound 6 (IC50: 0.64 μM) containing 5 fluorine atoms. The strongest antiproliferative effect on A549 cells was achieved with compound 5 (PI: 4.95) carrying 2 fluorine atoms. Apoptosis induction was effective in cell death. In addition to cleaved caspase-3 expression, chromatin condensation, marginalization, and apoptotic bodies were observed in the cells.

Conclusion: Some of the compounds tested showed high cytotoxic and antiproliferative effects, indicating that these compounds could be potential chemotherapeutic agent candidates for lung cancer. The result of immunofluorescence and immunohistochemical analysis showing that the cytotoxic effects have been induced by apoptosis is an important advantage.

1. Siegel R, Ma J, Zou Z, et al (2014). Cancer Statistics, 2014. CA Cancer J Clin, 64:9-29.
2. National Cancer Institute Funded Research Portfolio (NFRP) [Internet]. Bethesda (MD): National Cancer Institute; [cited 2014 April 4]. Available from http://fundedresearch.cancer.gov
3. Smith BD, Smith GL, Hurria A, et al (2009). Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol, 27(17):2758-65.
4. Halazonetis TD, Gorgoulis VG, Bartek J (2008). An oncogene-induced DNA damage model for cancer development. Science, 319(5868):1352-5.
5. Negrini S, Gorgoulis VG, Halazonetis TD (2010). Genomic instability an evolving hallmark of cancer. Nat Rev Mol Cell Biol, 11(3):220-8.
6. Reed JC, Jurgensmeier JM, Matsuyama S (1998). Bcl-2 family proteins and mito-chondria. Biochim Biophys Acta, 1366(1-2):127-37.
7. Green DR, Evan GI (2002). A matter of life and death. Cancer Cell, 1:19-30.
8. Navada S, Lai P, Schwartz AG, et al (2006). Temporal trends in small cell lung cancer: analysis of the national Surveillance Epi-demiology and End-Results (SEER) da-tabase. Journal of Clinical Oncology, 24(18_suppl): 7082-7082.7082-7082.
9. David M J, Bruce E Jn (2005). Small-cell lung cancer. Lancet, 366(9494):1385-96.
10. Isanbor C, O’Hagan D (2006). Fluorine in Medicinal Chemistry: A Review of Anti-Cancer Agents. ChemInform, 127(3):303-19.
11. Prakash A, Adhikari D (2011). Application of Schiff bases and their metal complex-es-A Review. Int J Chemtech Res, 3:1891-6.
12. Hiyama T (2000). Organofluorine Com-pounds. In: Chemistry and Application. Ed, H Yamamoto. Springer, New York, USA, pp. 137-77.
13. Filler R, Saha R (2009). Fluorine in Medici-nalChemistry: a Century of Progressand a 60-Year. Retrospective of SelectedHigh-lights. Future Med Chem, 1(5):777-91.
14. Ojima I (2013). Exploration of Fluorine Chemistry at the Multidisciplinary Inter-faceof Chemistry and Biology. J Org Chem, 78(13):6358-83.
15. Hagmann WK (2008). The many roles for fluorine in medicinal chemistry. J Med Chem, 51(15):4359-69.
16. Kim T, Zhu L, Al-Kaysi RO, et al (2014). Organic photomechanical materials. Chemphyschem, 15(3):400-14.
17. Abad A, Agullo C, Cunat AC, et al (2010). ChemInform Abstract: An Efficient Ste-reoselective Synthesis of Stypodiol (IX) and Epistypodiol (XI). ChemInform, 29(50):218-9.
18. Welch JT, Eswarakrishnan S (1991). Fluorine in Bioorganic Chemistry. John Wiley and Sons. Chichester.
19. Harper DB, O'Hagan D (1994). The fluori-nated natural products. Nat Prod Rep, 11(2):123-33.
20. Kamisawa T, Wood LD, Itoi T, et al (2016). Pancreatic cancer. Lancet, 388(10039):73-85.
21. Oettle H, Neuhaus P, Hochhaus A, et al (2013). Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients withresected pancreatic cancer: the CONKO-001 randomized trial. JAMA, 310(14):1473-81.
22. Murtaza G, Mumtaz A, Khan FA, et al (2014). Recent pharmacological advance-ments in Schiff bases: a review. Acta Pol Pharm, 71(4):531-5.
23. Gurol AO, Kasim V, Suzergoz F (2017). An-tiproliferative effects of fluorine substitute 3, 5-di-tert-butylphenol bearing Schiff ba-ses using CFSE-based cell proliferation assay. Curr Sci, 112:619-24.
24. Ejidike IP, Ajibade PA (2016). Ruthenium (III) Complexes of Heterocyclic Triden-tate (ONN) Schiff Base: Synthesis, Char-acterization and its Biological Properties as an Antiradical and Antiproliferative Agent. Int J Mol Sci, 17(1):60.
Files
IssueVol 50 No 3 (2021) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijph.v50i3.5596
Keywords
Schiff bases IC50 A549 Lung cancer Apoptosis

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
SAK HA, SÜZERGÖZ F, KASUMOV VT, GÜROL AO. Anticancer Properties of Fluorinated Aminophenylhydrazines on A549 Lung Carcinoma Cell Line. Iran J Public Health. 2021;50(3):550-556.