The Effects of Sulphanomide-E Derivative on Carnitine Metabolism of Cervix Cancer Cells

Öz

Introduction: Cervical cancer is one of the most common types of cancer in women worldwide. Recent studies have shown that metabolic programming can support cervical cancer treatment by increasing sensitivity to chemotherapy and radiotherapy. Therefore, the investigation of new treatment agents targeting the metabolism of cervical cancer is of great importance in terms of improving treatment outcomes and developing new strategies. In our previous studies, we determined that Sulfanomide-E derivative has an apoptotic effect on HELA cells. In this study, we aimed to investigate the effects of Sulfanomide-E on carnitine metabolism in HELA cells. Method: HELA cells were used in our study and the cytotoxic and apoptotic effects of Sulfanomide-E were investigated. A dose of 25 μg/ml Sulfanomide-E was applied to HELA cells and the cells were incubated for 24 hours. In order to determine the changes in carnitine metabolism, a total of 27 carnitine and acylcarnitine derivatives were analyzed using LC-MS/MS. The obtained data were analyzed with SPSS 25.0 program. Findings: As a result of the analyses, a significant increase was observed in all carnitine and acylcarnitine derivatives in the Sulfanomide-E applied groups compared to the control group. These findings indicate that Sulfanomide-E has an effect on carnitine metabolism and these metabolic changes may be important in terms of response to treatment. Conclusion: This study reveals that Sulfanomide-E affects carnitine metabolism in HELA cells and exhibits apoptotic effects. The obtained data suggest that these changes in carnitine metabolism may provide a new understanding of the potential benefits of metabolic programming in the treatment of cervical cancer. Therefore, the role of agents such as Sulfanomide-E in the treatment of cervical cancer should be supported by more detailed studies.

Anahtar Kelimeler

• Cervical cancer
• carnitine
• HELA cell line
• sulfanilamide
• LC-MS/M

Kaynakça

1. 1.Anand U, Dey A, Chandel AKS, et al. Cancerchemotherapy and beyond: Current status, drugcandidates, associated risks and progress intargeted therapeutics. Genes & Diseases.2023;10(4): 1367-1401.
2. 2.Siegel RL, Giaquinto AN, Jemal A. Cancer statistics,2024. CA: A cancer journal for clinicians. 2024;74(1).
3. 3.Pimple S, Mishra G. Cancer cervix: Epidemiologyand disease burden. Cytojournal. 2022;19.
4. 4.Baseman JG, Koutsky LA. The epidemiology ofhuman papillomavirus infections. 2005; 32: 16-24.
5. 5.Castellsagué X, Díaz M, De Sanjosé S, et al.Worldwide human papillomavirus etiology ofcervical adenocarcinoma and its cofactors:implications for screening and prevention. Journalof the National Cancer Institute. 2006; 98(5): 303-15.
6. 6.Mokhtari R B, Homayouni T S, Baluch N, et al.Combination therapy in combating cancer.Oncotarget. 2017; 8(23): 38022-43.
7. 7.Debela D T, Muzazu S G, Heraro KD, et al. Newapproaches and procedures for cancer treatment:Current perspectives. SAGE open medicine. 2021; 9:1-10.
8. 8.Ovung A, Bhattacharyya J. Sulfonamide drugs:Structure, antibacterial property, toxicity, andbiophysical interactions. Biophysical reviews. 2021;13(2): 259-72.

9. 9.Tapera M, Kekeçmuhammed H, Tüzün B, et al.Synthesis, carbonic anhydrase inhibitory activity,anticancer activity and molecular docking studies ofnew imidazolyl hydrazone derivatives. Journal ofmolecular structure. 2022; 1269: 133816.
10. 10.Hamed FM, Hassan BA, Abdulridha MM. Theantitumor activity of sulfonamides derivatives. Int. J. Pharm. Res. 2020; 12: 2512-19.
11. 11.Virmani M A, Cirulli M. The role of l-carnitine inmitochondria, prevention of metabolic inflexibilityand disease initiation. International journal ofmolecular sciences.2022; 23(5): 2717.
12. 12.Xu Y, Jiang W, Chen G, et al. L-carnitine treatmentof insulin resistance: A systematic review and meta-analysis. Advances in Clinical and ExperimentalMedicine.2017; 26 (2): 333-38.
13. 13.Anand U, Dey A, Chandel A K S, et al. Cancerchemotherapy and beyond: Current status, drugcandidates, associated risks and progress intargeted therapeutics. Genes & Diseases.2023;10(4):1367-1401.
14. 14.Singh S, Lomelino CL, Mboge MY, Frost SC,McKenna R. Cancer drug development of carbonicanhydrase inhibitors beyond the active site.Molecules.2018; 23(5): 1045.
15. 15.Ronca R, Supuran CT. Carbonic anhydrase IX: Anatypical target for innovative therapies in cancer.Biochimica et Biophysica Acta (BBA)-Reviews onCancer.2024;189120.
16. 16.Hsin MC, Hsieh Y H, Hsiao Y H, et al. Carbonicanhydrase IX promotes human cervical cancer cellmotility by regulating PFKFB4 expression. Cancers.2021; 13(5): 1174.
17. 17.Lieskovska J, Opavský R, Zacikova L, et al. Studyof in vitro conditions modulating expression ofMN/CA IX protein in human cell lines derived fromcervical carcinoma. Neoplasma.1999; 46(1): 17-24.
18. 18.Lee SH, Griffiths JR. How and why are cancersacidic? Carbonic anhydrase IX and the homeostaticcontrol of tumour extracellular pH.Cancers.2020;12(6):1616.
19. 19.Seyfried TN, Huysentruyt LC. On the origin ofcancer metastasis. Critical Reviews™ inOncogenesis. 2013; 18(1-2).
20. 20.Temiz E, Koyuncu I, Durgun M, et al. Inhibition ofcarbonic anhydrase IX promotes apoptosis throughintracellular pH level alterations in cervical cancercells. International journal of molecularsciences.2021; 22(11): 6098.
21. 21.Kreuzaler P, Panina Y, Segal J, Yuneva M. Adaptand conquer: Metabolic flexibility in cancer growth,invasion and evasion. Molecular metabolism.2020;33: 83-101.
22. 22.Console L, Scalise M, Mazza T, et al. Carnitinetraffic in cells. Link with cancer. Frontiers in Cell and Developmental Biology. 2020; 8: 583850.
23. 23.Melone M AB, Valentino A, Margarucci S, et al.The carnitine system and cancer metabolicplasticity. Cell death & disease.2018;9(2): 228.
24. 24.Farahzadi R, Hejazi MS, Molavi O, et al. Clinicalsignificance of carnitine in the treatment of cancer:from traffic to the regulation. Oxidative Medicineand Cellular Longevity.2023; (1): 9328344.
25. 25.Longo N, Frigeni M, Pasquali M. Carnitinetransport and fatty acid oxidation. Biochimica etBiophysica Acta (BBA)-Molecular CellResearch.2016; 1863(10):2422-35.