Evaluation of the Interactions of Cabozantinib with Topoisomerase Enzymes by in vitro Enzyme Activity Assays, and its Effects on Cancer Cell Proliferation

Feyza Oflaz; Naz Ünal; Burcin Gungor; Pakize Cantürk

doi:10.17776/csj.1376788

EN

Evaluation of the Interactions of Cabozantinib with Topoisomerase Enzymes by in vitro Enzyme Activity Assays, and its Effects on Cancer Cell Proliferation

Abstract

The discovery of many drugs in recent years provides a definitive solution in the treatment of various diseases, but today, despite the discovery of many effective anticancer drugs, there are various types of cancer that have limitations in treatment and are still not completely curable. Since most of these limitations are due to cancer cells gaining resistance or compounds only being effective in certain types of cancer cells, the search for more effective anticancer drugs that are also effective in these types of cancer is inevitable. Cabozantinib is in medical use as a highly effective anticancer drug in various types of cancer, such as medullary thyroid cancer and kidney cancer. The anticancer properties of the Cabozantinib compound have attracted more attention in recent years, however, more studies are needed to define the anticancer activities of this compound. In our study, the interactions of Cabozantinib with topoisomerase enzymes, were demonstrated through in vitro enzyme activity tests, and the anti-proliferative effect of Cabozantinib was studied on MCF7, A549 and PC3 cell lines. By analyzing the interactions of the Cabozantinib with topoisomerases, the action mechanisms of the compound at the molecular level was evaluated.

Keywords

Supporting Institution

TÜBİTAK-2209A ve CÜBAP

Project Number

TÜBİTAK-2209A-(1919B011701745) ve CÜBAP (ECZ018)

References

[1] Wang J.C., Cellular roles of DNA topoisomerases: a molecular perspective, Nat Rev Mol Cell Biol., 3 (2002) 430-440.
[2] Carey J.F., Schultz S.J., Sisson L., Fazzio T.G., Champoux J.J., DNA relaxation by human topoisomerase I occurs in the closed clamp conformation of the protein, Proc Natl Acad Sci USA, 100 (10) (2003) 5640-5645.
[3] Skok Ž., Zidar N., Kikelj D., Ilaš J., Dual Inhibitors of Human DNA Topoisomerase II and Other Cancer-Related Targets, J Med Chem., 63 (2020) 884-904.
[4] Nitiss J.L., Investigating the biological functions of DNA topoisomerases in eukaryotic cells, Biochim Biophys Acta, 1400 (1-3) (1998) 63-81.
[5] Bjornsti M.A., Osheroff N., Introduction to DNA Topoisomerases, Methods Mol Biol., 94 (1999) 1-8.
[6] Pommier Y., Leo E., Zhang H., Marchand C., DNA topoisomerases and their poisoning by anticancer and antibacterial drugs, Chem Biol. 17 (2010) 421-433.
[7] Swedan H.K., Kassab A.E., Gedawy E.M., Elmeligie S.E., Topoisomerase II inhibitors design: Early studies and new perspectives, Bioorg Chem. 136 (2023) 106548.
[8] Champoux J.J., DNA Topoisomerases: Structure, Function, and Mechanism, Annu Rev Biochem, 70 (2001) 369-413.

[9] Cinelli M.A., Topoisomerase 1B poisons: Over a half-century of drug leads, clinical candidates, and serendipitous discoveries, Med Res Rev. 39 (2019) 1294-1337.
[10] Baglini E., Salerno S., Barresi E., Robello M., Da Settimo F., Taliani S., Marini A.M., Multiple Topoisomerase I (TopoI), Topoisomerase II (TopoII) and Tyrosyl-DNA Phosphodiesterase (TDP) inhibitors in the development of anticancer drugs, Eur J Pharm Sci., 156 (2021) 105594.
[11] Madkour M.M., Ramadan W.S., Saleh E., El-Awady R., Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors, Ann Med. 55 (1) (2023) 2203946
[12] Pommier Y., Thomas A., New Life of Topoisomerase I Inhibitors as Antibody-Drug Conjugate Warheads, Clin. Cancer Res., 29 (2023) 991-993.
[13] Syrios J., Kouroussis C., Kotsakis A., Kentepozidis N., Kontopodis E., Kalbakis K., Vardakis N.,. Hatzidaki D, Polyzos A., Georgoulias V., Combination of weekly topotecan and gemcitabine as a salvage treatment in patients with recurrent ovarian cancer: a phase I study, Minerva Ginecol., 71 (3) (2019) 182-190.
[14] Kang J.H., Lee K.H., Kim D.W., Kim S.W., Kim H.R., Kim J.H., Choi J.H., An H.J., Kim J.S., Jang J.S., Kim B.S., Kim H.T., A randomised phase 2b study comparing the efficacy and safety of belotecan vs. topotecan as monotherapy for sensitive-relapsed small-cell lung cancer, Br J Cancer, 124 (2021) 713-720.
[15] Bax B.D., Murshudov G., Maxwell A., Germe T., DNA Topoisomerase Inhibitors: Trapping a DNA-Cleaving Machine in Motion, J Mol Biol., 431 (2019) 3427-3449.
[16] Martín-Encinas E., Selas A., Palacios F., Alonso C., The design and discovery of topoisomerase I inhibitors as anticancer therapies, Expert Opin Drug Discov., 17 (2022) 581–601.
[17] Roos W.P., Kaina B., DNA damage-induced cell death: From specific DNA lesions to the DNA damage response and apoptosis, Cancer Lett. 332 (2013) 237-248.
[18] Mahajan K.,. Mahajan N.P, Cross talk of tyrosine kinases with the DNA damage signaling pathways, Nucleic Acids Res., 43 (2015) 10588-10601.
[19] Yang P.W., Liu Y.C., Chang Y.H., Lin C.C., Huang P.M., Hua K.T., Lee J.M., Hsieh M.S., Cabozantinib (XL184) and R428 (BGB324) Inhibit the Growth of Esophageal Squamous Cell Carcinoma (ESCC), Front Oncol., 9 (2019) 1138.
[20] Esteban-Villarrubia J., Soto-Castillo J.J., Pozas J., Román-Gil M.S., Orejana-Martín I., Torres-Jiménez J., Carrato A., Alonso-Gordoa T., Molina-Cerrillo J., Tyrosine kinase receptors in oncology, Int J Mol Sci., 21 (2020) 1–48.
[21] Lyseng-Williamson K.A., Cabozantinib as first-line treatment in advanced renal cell carcinoma: a profile of its use, Drugs Ther Perspect., 34 (2018) 457-465.
[22] Karmacharya U., Guragain D., Chaudhary P., Jee J.G., Kim J.A., Jeong B.S., Novel pyridine bioisostere of cabozantinib as a potent c-met kinase inhibitor: Synthesis and anti-tumor activity against hepatocellular carcinoma, Int J Mol Sci., 22 (18) (2021) 9685.
[23] Zhang G.N., Zhang Y.K., Wang Y.J., Barbuti A.M., Zhu X.J., Yu X.Y., Wen A.W., Wurpel J.N.D., Chen Z.S., Modulating the function of ATP-binding cassette subfamily G member 2 (ABCG2) with inhibitor cabozantinib, Pharmacol Res., 119 (2017) 89-98.
[24] Senarisoy M., Canturk P., Zencir S., Baran Y., Topcu Z., Gossypol Interferes with Both Type I and Type II Topoisomerase Activities Without Generating Strand Breaks, Cell Biochem Biophys., 66 (2013) 199-204.
[25] Nitiss J.L., Topoisomerase Assays, Curr Protoc Pharmacol., 3 (3-1) (1998) 1934-8282
[26] Canturk P., Kucukoglu K., Topcu Z., Gul M.,. Gul H.I, Effect of Some Bis Mannich Bases and Corresponding Piperidinols on DNA Topoisomerase I, Arzneimittelforschung, 58 (12) (2008) 686-691.
[27] Liang X., Wu Q., Luan S., Yin Z., He C., Yin L., Zou Y., Yuan Z., Li L., Song X., He M., Lv C., Zhang W., A comprehensive review of topoisomerase inhibitors as anticancer agents in the past decade, Eur J Med Chem., 171 (2019) 129-168.
[28] Pommier Y., Nussenzweig A., Takeda S., Austin C., Human topoisomerases and their roles in genome stability and organization, Nat Rev Mol Cell Biol., 23 (2022) 407-427.
[29] Capranico G., Binaschi M., DNA sequence selectivity of topoisomerases and topoisomerase poisons, Biochim Biophys Acta., 1400 (1998) 185-194.
[30] Xu J., Higgins M.J., Tolaney S.M., Come S.E., Smith M.R., Fornier M., Mahmood U., Baselga J.,. Yeap B.Y, Chabner B.A., Isakoff S.J, A Phase II Trial of Cabozantinib in Hormone Receptor-Positive Breast Cancer with Bone Metastases, Oncologist, 25 (2020) 652-660.
[31] Piccaluga P.P., Cascianelli C., Inghirami G., Tyrosine kinases in nodal peripheral T-cell lymphomas, Front Oncol., 13 (2023) 1099943.
[32] Maroto P., Porta C., Capdevila J., Apolo A.B., Viteri S., Rodriguez-Antona C., Martin L., Castellano D., Cabozantinib for the treatment of solid tumors: a systematic review, Ther Adv Med Oncol., 14 (2022) 17588359221107112.
[33] Rizzo A., Brandi G., Biochemical predictors of response to immune checkpoint inhibitors in unresectable hepatocellular carcinoma, Cancer Treat Res Commun., 27 (2021) 100328.
[34] Konstantinopoulos P.A., Brady W.E., Farley J., Armstrong A., Uyar D.S., Gershenson D.M., Phase II study of single-agent cabozantinib in patients with recurrent clear cell ovarian, primary peritoneal or fallopian tube cancer (NRG-GY001), Gynecol Oncol., 150 (2018) 9-13.
[35] Alhazzani K., Alsahli M., Alanazi A.Z., Algahtani M., Alenezi A.A., Alhoshani A., Alqinyah M., Alhamed A.S., Alhosaini K., Augmented antitumor effects of erlotinib and cabozantinib on A549 non-small cell lung cancer: In vitro and in vivo studies, Saudi Pharm J., 31 (2023) 101756.

Details

Primary Language

English

Subjects

Enzymes , Basic Pharmacology , Pharmacology and Pharmaceutical Sciences (Other)

Journal Section

Research Article

Authors

Feyza Oflaz
0000-0002-2131-6982
Türkiye

Naz Ünal
0009-0007-3327-0428
Türkiye

Burcin Gungor
0000-0001-7725-5835
Türkiye

Pakize Cantürk ^*
0000-0001-8623-784X
Türkiye

Publication Date

December 28, 2023

Submission Date

October 16, 2023

Acceptance Date

December 15, 2023

Published in Issue

Year 2023 Volume: 44 Number: 4

DOI

https://doi.org/10.17776/csj.1376788

IZ

https://izlik.org/JA89HF72ZB

Cite

RIS / Bibtex

APA

Oflaz, F., Ünal, N., Gungor, B., & Cantürk, P. (2023). Evaluation of the Interactions of Cabozantinib with Topoisomerase Enzymes by in vitro Enzyme Activity Assays, and its Effects on Cancer Cell Proliferation. Cumhuriyet Science Journal, 44(4), 650-655. https://doi.org/10.17776/csj.1376788

Evaluation of the Interactions of Cabozantinib with Topoisomerase Enzymes by in vitro Enzyme Activity Assays, and its Effects on Cancer Cell Proliferation

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Keywords

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