Effects of Chemohormonal Therapy on Oxidant and Antioxidant Systems in Patients with Metastatic Castration- Resistant Prostate Cancer

Year 2024, , 1 - 13, 25.02.2025

Neslihan Yüce , Muhammed Kökpınar , Esra Laloğlu , Hilal Kiziltunç Özmen , Aykut Turhan , Mahsa Bayrami

https://doi.org/10.5281/zenodo.14932604

Abstract

Objective: The aim of this study was to investigate the effects of chemohormonal therapy on catalase (CAT), superoxide
dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), arylesterase (ARE), paraoxonase (PON), myeloperoxidase
(MPO), malondialdehyde (MDA), total antioxidant status (TAS), total oxidant status (TOS) in patients with metastatic
castration-resistant prostate cancer (MCCRPC). The aim of this study was to investigate the effect of chemohormonal treatment
and treatment resistance on oxidant and antioxidant system in cancer and prostate cancer through oxidative stress index (OSI)
parameters and to show that it may have a predictive value in the diagnosis, prognosis and treatment of the disease. Material
and method: This study included 112 patients diagnosed with prostate cancer and 30 healthy individuals (control group) who
were admitted to the Departments of Medical Oncology and Radiation Oncology of Atatürk University Medical Faculty
Hospital. Patients were divided into four groups according to the treatment protocol. Patients received androgen suppression
therapy, secondary hormone therapy and non-hormone therapy (chemoteropathic drugs) respectively (as resistance
developed). The first group was sensitive to androgen suppression therapy (ADT), the second group was resistant to androgen
suppression therapy and sensitive to chemotherapeutic agents. The third group was the group that developed resistance to
chemotherapeutics. The fourth group was patients who were diagnosed with prostate cancer and did not receive treatment.
CAT, SOD, tGSH, GPx, GPx, ARE, PON, MPO and MDA levels were analyzed by manual antioxidant methods in patient and
control serum samples, while TAS, TOS and OSI levels were analyzed by commercially purchased kits and according to the Erel
method. Results: CAT, ARE, MPO, TAS, TOS and OSI parameters showed significant differences between the groups (p<0.05),
while SOD, tGSH, GPx, MDA and PON parameters showed no significant differences between the groups. Conclusion: This is
a research study that will shed light on the effects of chemohormonal therapy and treatment resistance on oxidant and
antioxidant systems in cancer and prostate cancer and will fill the gap in the literature.

Keywords

Prostate, cancer, oxidant, antioxidant, chemohormonal therapy

Ethical Statement

Ethical Statement: The ethics committee approval of this study was obtained from Atatürk University Clinical Research Ethics Committee (Date:27.12.2024, No:2024/B.30.2.ATA.0.01.00/718).

References

• 1. Erzurumlu Y. Prostat Kanseri: Androjen Reseptörü Sinyal Mekanizması. Medical Journal of Süleyman Demirel University. 2021;28(1):187-98.
• 2. Özdoğan M. Türkiye Kanser İstatistikleri 2020. Erişim adresi: https://www drozdogan com/turkiye-kanseristatistikleri-2020/ Erişim tarihi. 2021;13.
• 3. Yıldızhan M, Dündar M, Ertek MŞ. Metastatik Prostat Kanserinde Aralıklı veya Devamlı Androjen Baskılama Tedavisi: Derleme. Üroonkoloji Bülteni. 2015;14(2).
• 4. Scher HI, Sawyers CL. Biology of progressive, castration- resistant prostate cancer: directed therapies targeting the androgen-receptor signaling axis. Journal of clinical oncology. 2005;23(32):8253-61.
• 5. Seçkiner İ. Kastrasyona Dirençli Prostat Kanseri Tedavisinde Son Gelişmeler. Journal of Reconstructive Urology. 2013;4(3):126-33.
• 6. Erbin A, Esen T. Kastrasyona Dirençli Prostat Kanserinde Tedavi 2024 [Available from: https://uroturk.org.tr/urolojiData/Books/520/kastrasyona- direncli-prostat-kanserinde-tedavi.pdf.
• 7. Ahmed Amar SA, Eryilmaz R, Demir H, Aykan S, Demir C. Determination of oxidative stress levels and some antioxidant enzyme activities in prostate cancer. The Aging Male. 2019;22(3):198-206.
• 8. Aslankoç R, Demirci D, İnan Ü, Yıldız M, Öztürk A, Çetin M, et al. Oksidatif stres durumunda antioksidan enzimlerin rolü- Süperoksit dismutaz (SOD), katalaz (CAT) ve glutatyon peroksidaz (GPX). Medical Journal of Süleyman Demirel University. 2019;26(3):362-9.
• 9. Özer ÖF, Güler EM, Selek Ş, Çoban G, Türk HM, Koçyiğit A. Akciğer, meme ve kolon kanserli hastalarda oksidatif stres parametrelerinin değişimi Variation of oxidative stress parameters in patients with lung, breast and colon cancer.
• 10. Mackness MI, Arrol S, Durrington PN. Paraoxonase prevents accumulation of lipoperoxides in low‐density lipoprotein. FEBS letters. 1991;286(1-2):152-4.
• 11. Eroglu M, Yilmaz N, Yalcinkaya S, Ay N, Aydin O, Sezer C. Enhanced HDL-cholesterol-associated anti-oxidant PON-1 activity in prostate cancer patients. The Kaohsiung journal of medical sciences. 2013;29(7):368-73.
• 12. Campo GM, Avenoso A, Campo S, Ferlazzo AM, Micali C, Zanghı̀ L, et al. Hyaluronic acid and chondroitin-4-sulphate treatment reduces damage in carbon tetrachloride-induced acute rat liver injury. Life sciences. 2004;74(10):1289-305.
• 13. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clinical chemistry. 1988;34(3):497-500.
• 14. Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Analytical biochemistry. 1968;25:192-205.
• 15. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. The Journal of laboratory and clinical medicine. 1967;70(1):158-69.
• 16. Gülcü F, Gürsu MF. Paraoksonaz ve aril esteraz aktivite ölçümlerinin standardizasyonu. Türk Biyokimya Dergisi. 2003;28(2):45-9.
• 17. Kaya H, Polat F, Çetinkaya R, Taysi S. Kronik hemodiyaliz hastalarinda serum paraoksanaz aktivitesi. Türk Nefroloji, Diyaliz ve Transplantasyon Dergisi. 2000;9(3).
• 18. Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. Journal of investigative dermatology. 1982;78(3):206-9.
• 19. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical biochemistry. 1979;95(2):351-8.
• 20. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clinical biochemistry. 2004;37(2):112-9.
• 21. Erel O. A new automated colorimetric method for measuring total oxidant status. Clinical biochemistry. 2005;38(12):1103-11.
• 22. Goolsby MJ. National Kidney Foundation Guidelines for chronic kidney disease: evaluation, classification, and stratification. Journal of the American Academy of Nurse Practitioners. 2002;14(6):238-42.
• 23. Cohen J. Statistical power analysis. Current directions in psychological science. 1992;1(3):98-101.
• 24. Yüksel B, Özkan AD. The role of citrus nobiletin on oxidative stress levels and superoxide dismutase activities in metastatic castration-resistant prostate cancer. Commagene Journal of Biology. 2021;5(1):84-9.
• 25. Seçkin D, Onur R, İlhan N, Ardıçoğlu A, İihan N. Prostat kanserli ve bening prostat hiperplazili hastalarda plazma vasküler endotelyal büyüme faktörü, oksidatif stres ve nitrik oksit ilişkisi. Fırat Üniversitesi Sağlık Bilimleri Tıp Dergisi. 2005;19:277-81.
• 26. Orhan N. Prostat Kanserli Hastalarda Oksidatif Stres ve Paraksonaz Aktivite Azalması. Konuralp Medical Journal. 2015;7(2):113-7.
• 27. Yıldırım A, Aslan Ş, Ocak T, Yildirim S, Kara F, Sahin Y. Travmalı hastalarda serum paraoksonaz/arilesteraz aktiviteleri ve malondialdehit düzeyleri. Eurasian J Med. 2007;39(2):85-8.
• 28. Sajjaboontawee N, Supasitthumrong T, Tunvirachaisakul C, Nantachai K, Snabboon T, Reiche EMV, et al. Lower thiol, glutathione, and glutathione peroxidase levels in prostate cancer: a meta-analysis study. The Aging Male. 2020;23(5):1533-44.
• 29. Arsova-Sarafinovska Z, Eken A, Matevska N, Erdem O, Sayal A, Savaser A, et al. Increased oxidative/nitrosative stress and decreased antioxidant enzyme activities in prostate cancer. Clinical biochemistry. 2009;42(12):1228-35.
• 30. Xiang M, Feng J, Geng L, Yang Y, Dai C, Li J, et al. Sera total oxidant/antioxidant status in lung cancer patients. Medicine. 2019;98(37):e17179.
• 31. Sincan S, Sincan G, Aşkın S, Kızıltunç A. Evaluation of Serum Paraoxonase, Myeloperoxidase, and HDL-Cholesterol Levels in Acute Myeloid Leukemia. Inflammation. 2023;46(6):2470-6.
• 32. Blatt EB, Parra K, Neeb A, Buroni L, Bogdan D, Yuan W, et al. Critical role of antioxidant programs in enzalutamide-resistant prostate cancer. Oncogene. 2023;42(30):2347-59.
• 33. Mondal D, Narwani D, Notta S, Ghaffar D, Mardhekar N, Quadri SS. Oxidative stress and redox signaling in CRPC progression: therapeutic potential of clinically-tested Nrf2-activators. Cancer Drug Resistance. 2021;4(1):96.
• 34. Eryilmaz IE, Egeli U, Cecener G. Association between the apoptotic effect of Cabazitaxel and its pro-oxidant efficacy on the redox adaptation mechanisms in prostate cancer cells with different resistance phenotypes. Cancer biology & therapy. 2024;25(1):2329368.