UDC: 616.006
BBC: 52.81
Bagdasaryan A.A., Blinova E.V., Kutorkina E.A., Pakina V.A., Epishkina A.A., Tumutolova O.M., Bogoslovskaya E.V., Semeleva E.V., Fedoseikin I.V., Blinov D.S.
Antitumor anti-EGFR action of a new derivative of 9-dihydroacridone
Keywords: gastric cancer, cell culture, epidermal growth factor receptor (EGFR), activity, suppressive concentration
The basis of modern strategies for the treatment of oncological diseases is the use of pharmaceutical products. A high frequency of refractoriness and formation of tumor cells' resistance to anti-EGFR drugs dictates the need to develop new active inhibitors of this intracellular kinase. The aim of this work was to study the antitumor effect of a new compound – a derivative of 9-Dihydroacridone on in vitro models of EGFR-expressing tumor cells. Material and methods. The compound of 9-aminium-3,3-dimethyl-3,4-dihydroacridine-1(2H)-one L-2-hydroxy-butandiovate (laboratory cipher of the developer institution LHT-17-19) was studied. Three cultures of human stomach cancer were used for the study. The analysis of tumor cell growth suppression was performed in a test with 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide, intracellular identification of the phosphorylated form of receptor tyrosine kinase – by Western blotting. Study results. The compound of 9-dihydroacridone dose-dependently suppresses the growth of EGFR-expressing tumor cells of human gastric cancer. Hs746T culture cells have the greatest sensitivity to the compound, MKN1 has the least. The antitumor activity of the substance is based on the ability to reduce the intracellular pool of the activated form of receptor tyrosine kinase EGFR. Conclusions. The obtained results allow enable to consider the compound LHT-17-19 as a promising compound for the subsequent preclinical study of its antitumor properties in animal systems.
References
- Blinova E.V., Epishkina A.V., Tumutolova O.M., Deryabina O.N. et al. Antitumor activity of the novel pyridine derivative.Research Results in Pharmacology, 2022, 8, pp. 81–86.
- Liu X., Wang P., Zhang C., Ma Z. Epidermal growth factor receptor (EGFR): A rising star in the era of precision medicine of lung cancer. Oncotarget. 2017, vol. 8, pp. 50209–
- Min H.Y., Lee H.Y. Molecular targeted therapy for anticancer treatment. Mol. Med., 2022, vol. 54, pp. 1670–1694.
- Mossman T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Immunol. Methods, 1983, vol. 65, pp. 55–63.
- Pérez-Herrero E., Fernández-Medarde A. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy. J. Pharm. Biopharm., 2015, vol. 93, pp. 52–79.
- Roy P.S., Saikia B.J. Cancer and cure: A critical analysis. Indian J. Cancer, 2016, vol. 53, no. 3, pp. 441–442.
- Sigismund S., Avanzato D., Lanzetti L. Emerging functions of the EGFR in cancer. Oncol., 2018, vol. 12, pp. 3–20.
- Varakumar P., Rajagopal K., Aparna B., Raman K. et al. Acridine as an Anti-Tumour Agent: A Critical Review. Molecules. 2022, vol. 28, id 193.
- Zhong L., Li Y., Xiong L., Wang W., Wu M. et al. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. Signal Transduct. Target. Ther., 2021, vol. 6, id 201.
About authors
- Bagdasaryan Alina A.
- Post-Graduate Student, Department of Clinical Pharmacology and Internal Diseases Propaedeutic, I.M. Sechenov First Moscow State Medical University (Sechenovskiy University), Russia, Moscow (alina8bagdasaryan@gmail.com; ORCID: https://orcid.org/0000-0003-3994-8766)
- Blinova Ekaterina V.
- Doctor of Medical Sciences, Professor, Department of Operative Surgery and Topographic Anatomy, I.M. Sechenov First Moscow State Medical University (Sechenovskiy University), Russia, Moscow (bev-sechenov@mail.ru; ORCID: https://orcid.org/0000-0003-0050-0251)
- Kutorkina Ekaterina A.
- Post-Graduate Student, Department of Clinical Pharmacology and Internal Diseases Propaedeutic, I.M. Sechenov First Moscow State Medical University (Sechenovskiy University), Russia, Moscow (slava-kpss@list.ru; ORCID: https://orcid.org/0009-0003-5572-4225)
- Pakina Victoria A.
- Candidate of Medical Sciences, Associate Professor, Department of Life Safety and Emergency Medicine, I.M. Sechenov First Moscow State Medical University (Sechenovskiy University), Russia, Moscow (shapo-viktoriya@mail.ru; ORCID: https://orcid.org/0000-0002-0509-5737)
- Epishkina Anna A.
- Post-Graduate Student, Department of Clinical Pharmacology and Internal Diseases Propaedeutic, I.M. Sechenov First Moscow State Medical University (Sechenovskiy University), Russia, Moscow (afina-nn@mail.ru; ORCID: https://orcid.org/0000-0001-7681-0382)
- Tumutolova Oksana M.
- Candidate of Medical Sciences, Associate Professor, Department of Obstetrics and Gynecology, National Research Ogarev Mordovia State University, Russia, Saransk (tumutolov@mail.ru; ORCID: https://orcid.org/0000-0002-8809-6507)
- Bogoslovskaya Evgenia V.
- Post-Graduate Student, Department of Clinical Pharmacology and Internal Diseases Propaedeutic, I.M. Sechenov First Moscow State Medical University (Sechenovskiy University), Russia, Moscow (jane221189@mail.ru; ORCID: https://orcid.org/0009-0005-4044-7776)
- Semeleva Elena V.
- Doctor of Medical Sciences, Associate Professor, Professor of the Department of Pharmacology, Clinical Pharmacology and Pharmaceutic Technology, National Research Ogarev Mordovia State University, Russia, Saransk (shtanina37@mail.ru; ORCID: https://orcid.org/0000-0001-6692-4968)
- Fedoseikin Ilya V.
- Doctor of Medical Sciences, Professor, Department of Life Safety and Emergency Medicine, I.M. Sechenov First Moscow State Medical University (Sechenovskiy University), Russia, Moscow (ilfedosei@yandex.ru; ORCID: https://orcid.org/0000-0003-1056-1955)
- Blinov Dmitry S.
- Doctor of Medical Sciences, Associate Professor, Head of Molecular and Clinical Pharmacology Department, Dmitry Rogachev National Research Medical Center of Pediatric Hematology, Oncology and Immunology, Russia, Moscow (blinov-pharm@yandex.ru; ORCID: https://orcid.org/0000-0002-8385-4356)
Article link
Bagdasaryan A.A., Blinova E.V., Kutorkina E.A., Pakina V.A., Epishkina A.A., Tumutolova O.M., Bogoslovskaya E.V., Semeleva E.V., Fedoseikin I.V., Blinov D.S. Antitumor anti-EGFR action of a new derivative of 9-dihydroacridone [Electronic resource] // Acta medica Eurasica. – 2023. – №3. P. 50-57. – URL: https://acta-medica-eurasica.ru/en/single/2023/3/6/. DOI: 10.47026/2413-4864-2023-3-50-57.