Research Article
BibTex RIS Cite

Cytotoxic Activity, Anti-migration and in silico Study of o-Coumaric acid on H1975 Non-small Cell Lung Cancer Cells

Year 2025, Volume: 46 Issue: 1, 35 - 40, 25.03.2025

Doğukan Mutlu

https://doi.org/10.17776/csj.1592097

Abstract

Lung cancer represents the most common malignancy and remains the primary cause of cancer-related deaths worldwide. Phenolic acids, including o-coumaric acid (OCA), have attracted considerable attention due to their diverse biological activities, particularly their anticancer properties. This study evaluates the cytotoxic activity of OCA, along with its anti-migration effects and molecular docking analysis. The in vitro cytotoxicity of OCA on H1975 cells was assessed using the MTT assay and Acridine orange/ethidium bromide (AO/EB) staining, while its impact on cell migration was analyzed through an in vitro scratch assay. OCA demonstrated cytotoxic activity against H1975 cells, with an IC50 value of 8.107 mM, and inhibited cell migration by 38%. Additionally, in silico molecular docking was performed to investigate its interaction with the epidermal growth factor receptor (EGFR). Although OCA exhibited notable binding interactions with EGFR, including hydrogen bonding and pi-alkyl interactions, its binding affinity (−5.9 kcal/mol) was lower compared to Gefitinib (−8.5 kcal/mol), a known EGFR inhibitor. These findings suggest that while OCA holds potential as a therapeutic agent against non-small cell lung cancer, its efficacy may be enhanced through structural modifications, including the synthesis of derivatives, warranting further research into its industrial and clinical applications

Keywords

o-Coumaric acid Lung cancer Cytotoxicity Anti-migration Molecular docking

References

  • [1] Siegel R.L., Giaquinto a.N., Jemal A., Cancer statistics, CA Cancer J. Clin., 74 (2024) 12–49.
  • [2] Siegel R.L., Miller K.D., Jemal A., Cancer statistics, CA Cancer J Clin., 68 (2018) 7-30.
  • [3] Anand U., Dey A., Chandel A.K.S., Sanyal R., Mishra A., Pandey D.K., De Falco V., Upadhyay A., Kandimalla R., Chaudhary A., Dhanjal J.K., Dewanjee S., Vallamkondu J., Pérez de la Lastra J.M., Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics, Genes Dis., 4 (2022) 1367-1401.
  • [4] Mead J.A.R., Smith J.N., Williams, R.T., Studies in detoxication. 72. The metabolism of coumarin and of o-coumaric acid, Biochemical Journal, 68 (1) (1958) 67.
  • [5] Sellami I.H., Maamouri E., Chahed T., Wannes W.A., Kchouk M.E., Marzouk B., Effect of growth stage on the content and composition of the essential oil and phenolic fraction of sweet marjoram (Origanum majorana L.), Ind Crops Prod., 30(3) (2009) 395-402.
  • [6] Cayan F., Deveci E., Tel-Cayan G., Duru M.E., Phenolic acid profile of six wild mushroom species by HPLC-DAD, Chem. Nat. Compd., 54 (2018) 985-986.
  • [7] Babich H, Visioli F., In vitro cytotoxicity to human cells in culture of some phenolics from olive oil, Farmaco., 58(5) (2003) 403-407.
  • [8] Sen A., Terzioglu G., Atmaca P., Celik G., Ozgun O., Arslan S., Modulatory actions of o-coumaric acid on carcinogen-activating cytochrome P450 isozymes and the potential for drug interactions in human hepatocarcinoma cells, Pharmaceutical Biology, 53(9) (2015) 1391–1398.
  • [9] Sen A., Atmaca P., Terzioglu G., Arslan S., Anticarcinogenic effect and carcinogenic potential of the dietary phenolic acid: o-coumaric acid, Nat Prod Commun., 8(9) (2013) 1269-74.
  • [10] Boutellaa S., Zellagui A., Öztürk M., Bensouici C., Ölmez Ö.T., Menakh M., Duru M.E., HPLC-DAD profiling and antioxidant activity of the butanol extract from aerial parts of Algerian L., Acta Scientifica Naturalis, 6(1) (2019) 8-16.
  • [11] Suleiman J.B., Mohamed M., Abu Bakar A.B., Nna V.U., Zakaria Z., Othman Z.A., Aroyehun A.B., Chemical profile, antioxidant properties and antimicrobial activities of Malaysian Heterotrigona itama bee bread, Molecules, 26(16) (2021) 4943.
  • [12] Sun Y., Ren G., Shi Q., Zhu H., Zhou N., Kong X., Jiang D., Liu C., Identification of a novel coumarins biosynthetic pathway in the endophytic fungus Fusarium oxysporum GU-7 with antioxidant activity, Appl. Environ. Microbiol., 89(1) (2023) e01601-22.
  • [13] Pao W., Miller V., Zakowski M., Doherty J., Politi K., Sarkaria I., Singh B., Heelan R., Rusch V., Fulton L., Mardis E., Kupfer D., Wilson R., Kris M., Varmus H., EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib, Proc. Natl. Acad. Sci. U.S.A., 101(36) (2004) 13306-13311.
  • [14] Pao W., Chmielecki J., Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer, Nat Rev Cancer, 10 (2010) 760-774.
  • [15] Rosell R., Carcereny E., Gervais R., Vergnenegre A., Massuti B., Felip E., Palmero R., Garcia-Gomez R., Pallares C., Sanchez J.M., Porta R., Cobo M., Garrido P., Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial, Lancet Oncol., 13 (2012) 239-246.
  • [16] Yılmaz C., Arslan S., Mutlu D., Konus M., Kayhan A., Kurt-Kızıldoğan A., Otur Ç., Ozok O., Kivrak A., Identification of 3-Bromo-1-Ethyl-1H-Indole as a Potent Anticancer Agent with Promising Inhibitory Effects on GST Isozymes, Anticancer Agents Med Chem., 21(10) (2021) 1292-1300.
  • [17] Konus M., Çetin D., Yılmaz C., Arslan S., Mutlu D., Kurt-Kızıldoğan A., Otur C., Ozok O., Algso M.A.S., Kivrak A., Synthesis, biological evaluation and molecular docking of novel thiophene‐based indole derivatives as potential antibacterial, GST inhibitor and apoptotic anticancer agents, ChemistrySelect, 5 (2020) 5809.
  • [18] Liu K., Liu P.C., Liu R., Wu X., Dual AO/EB staining to detect apoptosis in osteosarcoma cells compared with flow cytometry, Med Sci Monit Basic Res., 9 (2015) 15-20.
  • [19] Mutlu D., Seçme M., Arslan S., Effects of Usnic Acid on Cytotoxicity, Colony Formation and Migration in SK-UT-1 Human Uterine Leiomyosarcoma Cells, SDUFASJS, 18 (3) (2023) 195–202.
  • [20] Murail S., de Vries S.J., Rey J., Moroy G., Tufféry P., SeamDock: an interactive and collaborative online docking resource to assist small compound molecular docking, Front Mol Biosci., 8 (2021) 716466.
  • [21] Nair V.D., Panneerselvam K., Effect of o-coumaric acid on cytotoxicity and apoptosis in human breast adenocarcinoma MCF-7 cells, Prev Nutr Food Sci, 5 (2) (2015) 115-122.
  • [22] Cai X., Wang X., Li J., Chen S., Sun Z., O-Coumaric Acid Inhibits Proliferation, Migration, and Invasion of Prostate Cancer Cells by Targeting AR/β-Catenin Axis, Front. Oncol., 11 (2021) 679972.
  • [23] Jung S.H., Kim B.K., Park Y.K., Kim, K.S., Lee S.J., Kim J.R., Moon S. H., Cytotoxic activity of o-coumaric acid in glioblastoma cells is mediated via apoptosis induction and reactive oxygen species production, Toxicol. In Vitro, 26 (5) (2012) 699-709.
  • [24] Li C., Shi Y., Wang W., Li D., O-coumaric acid inhibits cell proliferation and induces apoptosis in colorectal cancer via inhibiting the TGF-β signaling pathway, IJCEM, 10 (10) (2017) 14116-14123.
  • [25] Gutiérrez Mercado Y.K., Mateos Díaz J.C., Ojeda Hernández D.D., López Gonzalez F.J., Reza Zaldivar E.E., Hernández Sapiens M.A., Gómez Pinedo U.A.; Estrada R.S., Macías Carballo M., Canales Aguirre A.A., Ortho-coumaric acid derivatives with therapeutic potential in a three-dimensional culture of the immortalised U-138 MG glioblastoma multiforme cell line, Neurol Perspect, 2 (2022) 19-30.
  • [26] Morgillo F., Della Corte C.M., Fasano M., Ciardiello F., Mechanisms of resistance to EGFR-targeted drugs: lung cancer, ESMO open, 1(3) (2016) e000060.
  • [27] Chung E.K., Yong S.H., Lee E.H., Kim E.Y., Chang Y.S., Lee S.H., New Targeted Therapy for Non-Small Cell Lung Cancer, Tuberc Respir Dis. (Seoul)., 86 (1) (2023) 1-13.

o-Kumarik Asidin H1975 Küçük Hücreli Olmayan Akciğer Kanseri Hücreleri Üzerinde Sitotoksik Aktivitesi, Anti-migrasyon ve in-Silico Çalışması

Year 2025, Volume: 46 Issue: 1, 35 - 40, 25.03.2025

Doğukan Mutlu

https://doi.org/10.17776/csj.1592097

Abstract

Akciğer kanseri, dünya genelinde en yaygın kanser türü ve kansere bağlı ölümlerin önde gelen nedenidir. Fenolik asitler, özellikle antikanser özellikleri nedeniyle çeşitli biyolojik aktiviteleriyle dikkat çeken bir grup bileşiktir. Bu çalışma, o-kumarik asidin (OCA) sitotoksik aktivitesini, anti-migrasyon etkilerini ve moleküler yerleştirme analizini değerlendirmektedir. H1975 hücrelerindeki OCA'nın in vitro sitotoksisitesi, MTT testi ve AO/EB boyaması kullanılarak değerlendirilirken, hücre göçü üzerindeki etkisi in vitro yara iyileşme testi (scratch assay) ile analiz edilmiştir. OCA, H1975 hücrelerine karşı sitotoksik aktivite göstermiş, IC50 değeri 8.107 mM olarak belirlenmiş ve hücre göçünü %38 oranında inhibe etmiştir. Ayrıca, in silico moleküler yerleştirme analizi, epidermal büyüme faktörü reseptörü (EGFR) ile etkileşimini araştırmak için gerçekleştirilmiştir. Sonuçlar, OCA'nın EGFR'ye güçlü bir bağlanma afinitesi sergilediğini ortaya koymuştur. Bu bulgular, OCA'nın küçük hücreli dışı akciğer kanserine karşı terapötik bir ajan olarak potansiyele sahip olduğunu ve endüstriyel ve klinik uygulamalarına yönelik daha fazla araştırma yapılması gerektiğini göstermektedir.

Keywords

o-Kumarik asit akciğer kanseri sitotoksisite anti-göç moleküler yerleştirme

References

  • [1] Siegel R.L., Giaquinto a.N., Jemal A., Cancer statistics, CA Cancer J. Clin., 74 (2024) 12–49.
  • [2] Siegel R.L., Miller K.D., Jemal A., Cancer statistics, CA Cancer J Clin., 68 (2018) 7-30.
  • [3] Anand U., Dey A., Chandel A.K.S., Sanyal R., Mishra A., Pandey D.K., De Falco V., Upadhyay A., Kandimalla R., Chaudhary A., Dhanjal J.K., Dewanjee S., Vallamkondu J., Pérez de la Lastra J.M., Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics, Genes Dis., 4 (2022) 1367-1401.
  • [4] Mead J.A.R., Smith J.N., Williams, R.T., Studies in detoxication. 72. The metabolism of coumarin and of o-coumaric acid, Biochemical Journal, 68 (1) (1958) 67.
  • [5] Sellami I.H., Maamouri E., Chahed T., Wannes W.A., Kchouk M.E., Marzouk B., Effect of growth stage on the content and composition of the essential oil and phenolic fraction of sweet marjoram (Origanum majorana L.), Ind Crops Prod., 30(3) (2009) 395-402.
  • [6] Cayan F., Deveci E., Tel-Cayan G., Duru M.E., Phenolic acid profile of six wild mushroom species by HPLC-DAD, Chem. Nat. Compd., 54 (2018) 985-986.
  • [7] Babich H, Visioli F., In vitro cytotoxicity to human cells in culture of some phenolics from olive oil, Farmaco., 58(5) (2003) 403-407.
  • [8] Sen A., Terzioglu G., Atmaca P., Celik G., Ozgun O., Arslan S., Modulatory actions of o-coumaric acid on carcinogen-activating cytochrome P450 isozymes and the potential for drug interactions in human hepatocarcinoma cells, Pharmaceutical Biology, 53(9) (2015) 1391–1398.
  • [9] Sen A., Atmaca P., Terzioglu G., Arslan S., Anticarcinogenic effect and carcinogenic potential of the dietary phenolic acid: o-coumaric acid, Nat Prod Commun., 8(9) (2013) 1269-74.
  • [10] Boutellaa S., Zellagui A., Öztürk M., Bensouici C., Ölmez Ö.T., Menakh M., Duru M.E., HPLC-DAD profiling and antioxidant activity of the butanol extract from aerial parts of Algerian L., Acta Scientifica Naturalis, 6(1) (2019) 8-16.
  • [11] Suleiman J.B., Mohamed M., Abu Bakar A.B., Nna V.U., Zakaria Z., Othman Z.A., Aroyehun A.B., Chemical profile, antioxidant properties and antimicrobial activities of Malaysian Heterotrigona itama bee bread, Molecules, 26(16) (2021) 4943.
  • [12] Sun Y., Ren G., Shi Q., Zhu H., Zhou N., Kong X., Jiang D., Liu C., Identification of a novel coumarins biosynthetic pathway in the endophytic fungus Fusarium oxysporum GU-7 with antioxidant activity, Appl. Environ. Microbiol., 89(1) (2023) e01601-22.
  • [13] Pao W., Miller V., Zakowski M., Doherty J., Politi K., Sarkaria I., Singh B., Heelan R., Rusch V., Fulton L., Mardis E., Kupfer D., Wilson R., Kris M., Varmus H., EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib, Proc. Natl. Acad. Sci. U.S.A., 101(36) (2004) 13306-13311.
  • [14] Pao W., Chmielecki J., Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer, Nat Rev Cancer, 10 (2010) 760-774.
  • [15] Rosell R., Carcereny E., Gervais R., Vergnenegre A., Massuti B., Felip E., Palmero R., Garcia-Gomez R., Pallares C., Sanchez J.M., Porta R., Cobo M., Garrido P., Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial, Lancet Oncol., 13 (2012) 239-246.
  • [16] Yılmaz C., Arslan S., Mutlu D., Konus M., Kayhan A., Kurt-Kızıldoğan A., Otur Ç., Ozok O., Kivrak A., Identification of 3-Bromo-1-Ethyl-1H-Indole as a Potent Anticancer Agent with Promising Inhibitory Effects on GST Isozymes, Anticancer Agents Med Chem., 21(10) (2021) 1292-1300.
  • [17] Konus M., Çetin D., Yılmaz C., Arslan S., Mutlu D., Kurt-Kızıldoğan A., Otur C., Ozok O., Algso M.A.S., Kivrak A., Synthesis, biological evaluation and molecular docking of novel thiophene‐based indole derivatives as potential antibacterial, GST inhibitor and apoptotic anticancer agents, ChemistrySelect, 5 (2020) 5809.
  • [18] Liu K., Liu P.C., Liu R., Wu X., Dual AO/EB staining to detect apoptosis in osteosarcoma cells compared with flow cytometry, Med Sci Monit Basic Res., 9 (2015) 15-20.
  • [19] Mutlu D., Seçme M., Arslan S., Effects of Usnic Acid on Cytotoxicity, Colony Formation and Migration in SK-UT-1 Human Uterine Leiomyosarcoma Cells, SDUFASJS, 18 (3) (2023) 195–202.
  • [20] Murail S., de Vries S.J., Rey J., Moroy G., Tufféry P., SeamDock: an interactive and collaborative online docking resource to assist small compound molecular docking, Front Mol Biosci., 8 (2021) 716466.
  • [21] Nair V.D., Panneerselvam K., Effect of o-coumaric acid on cytotoxicity and apoptosis in human breast adenocarcinoma MCF-7 cells, Prev Nutr Food Sci, 5 (2) (2015) 115-122.
  • [22] Cai X., Wang X., Li J., Chen S., Sun Z., O-Coumaric Acid Inhibits Proliferation, Migration, and Invasion of Prostate Cancer Cells by Targeting AR/β-Catenin Axis, Front. Oncol., 11 (2021) 679972.
  • [23] Jung S.H., Kim B.K., Park Y.K., Kim, K.S., Lee S.J., Kim J.R., Moon S. H., Cytotoxic activity of o-coumaric acid in glioblastoma cells is mediated via apoptosis induction and reactive oxygen species production, Toxicol. In Vitro, 26 (5) (2012) 699-709.
  • [24] Li C., Shi Y., Wang W., Li D., O-coumaric acid inhibits cell proliferation and induces apoptosis in colorectal cancer via inhibiting the TGF-β signaling pathway, IJCEM, 10 (10) (2017) 14116-14123.
  • [25] Gutiérrez Mercado Y.K., Mateos Díaz J.C., Ojeda Hernández D.D., López Gonzalez F.J., Reza Zaldivar E.E., Hernández Sapiens M.A., Gómez Pinedo U.A.; Estrada R.S., Macías Carballo M., Canales Aguirre A.A., Ortho-coumaric acid derivatives with therapeutic potential in a three-dimensional culture of the immortalised U-138 MG glioblastoma multiforme cell line, Neurol Perspect, 2 (2022) 19-30.
  • [26] Morgillo F., Della Corte C.M., Fasano M., Ciardiello F., Mechanisms of resistance to EGFR-targeted drugs: lung cancer, ESMO open, 1(3) (2016) e000060.
  • [27] Chung E.K., Yong S.H., Lee E.H., Kim E.Y., Chang Y.S., Lee S.H., New Targeted Therapy for Non-Small Cell Lung Cancer, Tuberc Respir Dis. (Seoul)., 86 (1) (2023) 1-13.
There are 27 citations in total.

Details

Primary Language English
Subjects Molecular Docking, Cell Development, Proliferation and Death, Cancer Biology
Journal Section Natural Sciences
Authors

Doğukan Mutlu 0000-0003-3259-5822

Publication Date March 25, 2025
Submission Date November 27, 2024
Acceptance Date February 13, 2025
Published in Issue Year 2025Volume: 46 Issue: 1

Cite

APA Mutlu, D. (2025). Cytotoxic Activity, Anti-migration and in silico Study of o-Coumaric acid on H1975 Non-small Cell Lung Cancer Cells. Cumhuriyet Science Journal, 46(1), 35-40. https://doi.org/10.17776/csj.1592097
 Download Cover Image