Investigation of Caffeic Acid Effect on Human Cancer Cell Line and Some Enzymes

Abstract

Caffeic acid, a prominent antioxidant compound, has garnered significant attention in research due to its multifaceted properties, which include anti-inflammatory, antiobesogenic, antithrombotic, vasodilating, and antitumor activities. This study aims to comprehensively investigate the impact of caffeic acid on various metabolic enzymes (carbonic anhydrase I, II, IX, and glutathione reductase) through both in silico and in vitro approaches. Furthermore, in vitro experiments did conducted on the AGS (gastric cancer cell) line and the HaCaT (keratinocyte normal cell) line to elucidate the effects of caffeic acid in these cellular systems.

Keywords

• Caffeic acid
• carbonic anhydrase
• glutathione reductase
• cancer.

References

1. ABDEL-AZIZ AA-M, EL-AZAB AS, EKINCI D, SENTURK M, SUPURAN CT. 2015. Investigation of arenesulfonyl-2-imidazolidinones as potent carbonic anhydrase inhibitors. J Enzym Inhib Med Chem. 30(1):81-84.
2. AGUNLOYE OM, OBOH G, ADEMILUYI AO, ADEMOSUN AO, AKINDAHUNSI AA, OYAGBEMI AA, et al. 2019. Cardio-protective and antioxidant properties of caffeic acid and chlorogenic acid: mechanistic role of angiotensin converting enzyme, cholinesterase and arginase activities in cyclosporine induced hypertensive rats. Biomed Pharmacother. 109:450-458.
3. ARSLAN T, CELIK G, CELIK H, SENTURK M, YAYLI N, EKINCI D. 2016. Synthesis and Biological Evalution of Novel Bischalcone Derivatives as Carbonic Anhydrase Inhibitors. Archive der Pharmazie. 349(9):741-748.
4. ARSLAN T, TURKOGLU EA, SENTURK M, SUPURAN CT. 2016. Novel chalcone substituted benzenesulfonamides as inhibitors for human carbonic anhydrases. Bioorg Med Chem Lett. 26(24):5867-5870.
5. ARSLAN T, CEYLAN MB, BAS H, BIYIKLIOGLU Z, SENTURK M. 2020. Design, Synthesis, Characterization of Novel Peripherally Tetra 1,2,3-Triazole Substituted Phthalocyanines and Inhibitor Effect on Cholinesterases (AChE/BChE) and Carbonic Anhydrases (hCA I, II and IX). Dalton Trans. 49:203-209.
6. AYGUN B, SENTURK M, CINAN E, SIMSEK O, SAYYED MI, KARABULUT A. 2022. Determination of Biological Radioprotective Characteristics of some natural organic compounds for Radiation Shielding Applications. Radiochimica Acta. https://doi.org/10.1515/ract-2022-0028.
7. BALENDIRAN GK, DABUR R, FRASER D. 2004. The role of glutathione in cancer. Cell Biochem Funct 22:343-352.
8. BEUTLER E. 1984. Red cell metabolism. A manual of biochemical methods. Grune and Stratton Inc, Orlando. ISBN: 0808916726 9780808916727.

9. BOEHME CC, ARSCOTT LD, BECKERK, SCHIRMER RH, WILLIAMS CH. 2000. Kinetic characterization of glutathione reductase from the malarial parasite Plasmodium falciparum Comparison with the human enzyme. J Biol Chem. 275:37317-37323.
10. CAKMAK R, DURDAGI S, EKINCI D, SENTURK M, TOPAL G. 2011. Design, synthesis and biological evaluation of novel nitroaromatic compounds as potent glutathione reductase inhibitors. Bioorg Med Chem Lett. 21;5398-5402.
11. CHEN JH, HO CT. 1997. Antioxidant activities of caffeic acid and its related hydroxycinnamic acid compounds. J Agric Food Chem. 45:2374-2378.
12. COBAN TA, SENTURK M, CIFTCI M, KUFREVIOGLU OI. 2007. Effects of some metal ions on human erythrocyte glutathione reductase: an in vitro study. Protein Peptide Lett. 14(10)1027-1030.
13. COUTO N, WOOD J, BARBER J. 2016. The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Rad Biol Med. 95:27-42.
14. DEMIRDAG R, COMAKLI V, SENTURK M, EKINCI D, KUFREVIOGLU OI, SUPURAN CT. 2013. Purification and characterization of carbonic anhydrase from sheep kidney and effects of sulfonamides on enzyme activity. Bioorg Med Chem. 21(6):1522-1525.
15. DIZDAROGLU Y, ALBAY C, ARSLAN T, ECE A, TURKOGLU EA, EFE A, SENTURK M, SUPURAN CT, EKINCI D. 2020. Design, synthesis and molecular modelling studies of some pyrazole derivatives as carbonic anhydrase inhibitors. J Enzym Inhib Med Chem. 35(1):289-297.
16. ESPÍNDOLA KMM, FERREIRA RG, NARVAEZ LEM, SILVA ROSARIO ACR, DA SILVA AHM, SILVA AGB, VIEIRA AP, MONTEIRO MC. 2019. Chemical and Pharmacological Aspects of Caffeic Acid and Its Activity in Hepatocarcinoma. Front. Oncol. 9:541.
17. FIDAN I, SALMAS RE, ARSLAN M, SENTURK M, DURDAGI S, EKINCI D, SENTURK E, COSGUN S. SUPURAN CT. 2015. Carbonic anhydrase inhibitors: design, synthesis, kinetic, docking and molecular dynamics analysis of novel glycine and phenylalanine sulphonamide derivatives. Bioorg Med Chem. 23(23):7353-7358.
18. GENARO-MATTOS TC, MAURÍCIO ÂQ, RETTORI D, ALONSO A, HERMES-LIMA M. 2015. Antioxidant activity of caffeic acid against iron-induced free radical generation-A chemical approach. PLoS ONE. 10:e0129963.
19. GOULD KS, MARKHAM KR, SMITH RH, GORIS JJ. 2000. Functional role of anthocyanins in the leaves of Quintinia serrata A. Cunn. J Exp Bot. 51:1107-1115.
20. GRELLIER P, SARLAUSKAS J, ANUSEVICIUS Z, MAROZIENE A, HOUEE-LEVIN C, SCHREVEL J, CENAS N. 2001. Antiplasmodial activity of nitroaromatic and quinoidal compounds: redox potential vs. inhibition of erythrocyte glutathione reductase. Arch Biochem Biophys. 393:199-206.
21. ISIK S, VULLO D, DURDAGI S, EKINCI D, SENTURK M, CETIN A, SENTURK E, SUPURAN CT. 2015. Interaction of carbonic anhydrase isozymes I, II, and IX with some pyridine and phenol hydrazinecarbothioamide derivatives. Bioorg Med Chem Lett. 25(23):5636-5641.
22. KARPLUS PA, PAI EF, SCHULZ GE. 1989. A crystallographic study of the glutathione binding site of glutathione reductase at 0.3 nm resolution. Eur J Biochem. 178:693-703.
23. KOCANCI FG, HAMAMCIOGLU B, ASLIM B. 2017. The anti-AChE and antiproliferative Activities of Glaucium acutidentatum and Glaucium corniculatum Alkaloid Extracts. J App Pharm Sci. 7(8):191-200.
24. KOCAOGLU E, TALAZ O, CAVDAR H, SENTURK M, SUPURAN CT, EKINCI D. 2019. Determination of the inhibitory effects of N-methylpyrrole derivatives on glutathione reductase enzyme. J Enzym Inhib Med Chem. 34:51-54.
25. LEE KW, KANG NJ, KIM JH, LEE KM, LEE DE, HUR HJ, et al. 2008. Caffeic acid phenethyl ester inhibits invasion and expression of matrix metalloproteinase in SK-Hep1 human hepatocellular carcinoma cells by targeting nuclear factor kappa B. Genes Nutr. 2:319-322.
26. MCGLYNN KA, PETRICK JL, LONDON WT. 2015. Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability. Clin Liver Dis. 19(2):223-238.
27. NAGAOKA T, BANSKOTA AH, TEZUKA Y, SAIKI I, KADOTA S. 2002. Selective antiproliferative activity of caffeic acid phenethyl ester analogues on highly liver-Metastatic murine colon 26-L5 carcinoma cell line. Bioorganic Med Chem. 10:3351-3359.
28. RODRIGUES JL, ARAÚJO RG, PRATHER KLJ, KLUSKENS LD, RODRIGUES LR. 2015. Heterologous production of caffeic acid from tyrosine in Escherichia coli. Enzyme Microb Technol. 71:36-44.
29. SANNER MF. 1999. Python: a programming language for software integration and development. J Mol Graph Model. 17(1):57-61.
30. SANTACROCE G, GENTILE A, SORIANO S, NOVELLI A, LENTI MV, DI SABATINO A. 2023. Glutathione: Pharmacological aspects and implications for clinical use in non-alcoholic fatty liver disease. Front Med (Lausanne). 22;10:1124275.
31. SENTURK E, GELEN V, SENGUL E, SENTURK M, YILDIRIM S, TEKIN S. 2022. Determination of the Protective Effects of Hesperidin and Curcumin on the Inhibition Effect of 5-Fluorouracil in Mouse Kidney Carbonic Anhydrase Enzyme. Acta Physiol. 234:68.
32. SENTURK M, KUFREVIOGLU OI, CIFTCI M. 2008. Effects of some antibiotics on human erythrocyte glutathione reductase: An in vitro study, J Enzym Inhib Med Chem. 23(1):144-148.
33. SENTURK M, KUFREVIOGLU OI, CIFTCI M. 2009. Effects of some analgesic and anestethic drugs on human erythrocyte glutathione reductase: an in vitro study. J Enzym Inhib Med Chem. 24(2):420-424. SILVA T, OLIVEIRA C, BORGES F. 2014. Caffeic acid derivatives, analogs and applications: a patent review (2009-2013). Expert Opin Ther Pat. 24:1257-1270.
34. STRIEDINGER K, BARRUET E, POMERANTZ JH. 2021. Purification and preservation of satellite cells from human skeletal muscle. STAR Protoc. 29;2(1):100302.
35. SUPURAN CT. 2008. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nature Rev Drug Discov. 7:168-181.
36. SUPURAN CT. 2017. Carbonic anhydrase inhibition and the management of hypotoxic tumours. Metabolites. 7:48-61.
37. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017:7:42717.
38. TOSOVIC J. 2017. Spectroscopic features of caffeic acid: theoretical study. Kragujev J Sci. 3918025435:99-108.
39. TRAVERSO N, RICCIARELLI R, NITTI M, MARENGO B, FURFARO AL, PRONZATO MA, MARINARI UM, DOMENICOTTI C. 2013. Role of glutathione in cancer progression and chemoresistance. Oxid Med Cell Longev. 2013:972913.
40. TROTT O, OLSON AJ. 2010. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comp chem. 31(2):455-461.
41. URCAR H, SENTURK E, SENTURK M, GUL M, YILDIRIM S. 2016. Investigation of Effects of Some Catecholamines on The Activity of Carbonic Anhydrase Enzyme Purified From Bovine Kidney Tissue. Acta Physiol. 218:57. USTUNDAG H, SENTURK E, SENTURK M. 2022. Effect of White Noise and Light Exposure on Rat Testis Glutathione Reductase Enzyme. Acta Physiol. 234:79.
42. VERMA RP, HANSCH C. 2004. An approach towards the quantitative structure-activity relationships of caffeic acid and its derivatives. ChemBioChem. 5:1188-1195.
43. VERPOORTE JA, MEHTA S, EDSALL JT. 1967. Esterase activities of human carbonic anhydrases B and C. J Biol Chem. 242(18):4221-4229.
44. VULLO D., INNOCENTI A., NISHIMORI I., PASTOREK J., SCOZZAFAVA A., PASTOREKOVA S., SUPURAN CT. 2005. Carbonic anhydrase inhibitors. Inhibition of the transmembrane isozyme XII with sulfonamides-a new target for the design of antitumor and antiglaucoma drugs? Bioorg. Med. Chem. Lett. 15:963-969.
45. WON C, LEE CS, LEE JK, KIM TJ, LEE KH, YANG YM, et al. 2010. CADPE suppresses cyclin D1 expression in hepatocellular carcinoma by blocking IL-6-induced STAT3 activation. Anticancer Res. 30:481-488.
46. YAKAN H, BILIR G, ÇAKMAK Ş, TAŞ O, TÜRKÖZ KARAKULLUKÇU N, SOYDAN E, KUTUK H, GUCLU C, SENTURK M, ARSLAN T, OZTURK S, AKSAKAL E, EKINCI D. 2023. Inhibitory effects of sulfenimides on human and bovine carbonic anhydrase enzymes. J Enzyme Inhib Med Chem. 38(1):2194573.
47. YANG SY, HONG CO, LEE GP, KIM CT, LEE KW. 2013. The hepatoprotection of caffeic acid and rosmarinic acid, major compounds of Perilla frutescens, against t-BHP-induced oxidative liver damage. Food Chem Toxicol. 55:92-99.
48. ZHANG Z, WANG D, QIAO S, WU X, CAO S, WANG L, ET al. 2017. Metabolic and microbial signatures in rat hepatocellular carcinoma treated with caffeic acid and chlorogenic acid. Sci Rep. 7:4508.