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Genisteinin androjen-bağımsız PC3 prostat kanseri hücreleri üzerindeki etkisi

Year 2025, Volume: 50 Issue: 1, 231 - 240, 31.03.2025
https://doi.org/10.17826/cumj.1633575

Abstract

Amaç: Bu çalışma, genisteinin andojen-bağımsız prostat kanser hücrelerinde hücre sağkalımını ve migrasyonunu, apoptozu, reaktif oksijen türleri (ROS) oluşumunu, antioksidan protein Manganez Süperoksit Dismutaz (MnSOD) ekspresyonunu nasıl etkilediğini göstermeyi ve özellikle kastrasyona dirençli prostat kanser adjuvan tedavisi olası kullanımına ışık tutmayı amaçlamaktadır.
Gereç ve Yöntem: Hücreler, 24 ve 48. saatlerde genistein bulunmayan ve 0.5, 2.5, 5, 10 ve 50 µM konsantrasyonlarda genistein bulunan ortamlarda büyütüldü. Sonuçları değerlendirmek için hücre proliferasyon analizi, hücre migrasyon analizi, reaktif oksijen türleri üretim ölçümü, apoptoz tespiti ve MnSOD protein ekspresyon analizi yapıldı.
Bulgular: Bulgularımız, genisteinin PC3 hücreleri üzerinde bifazik etkileri olduğunu göstermiştir. Özellikle daha düşük-fizyolojik konsantrasyonlarda (0,5-10 µM) ılımlı bir uyarıcı özellik gösterdiği, daha yüksek, farmakolojik (50 µM) konsantrasyonda hücre sağkalımında düşüş ve hücre göçünde önemli bir kısıtlamaya sebep olduğu saptanmıştır.
Sonuç: Analiz sonuçları genisteinin, özellikle yüksek konsantrasyonda, androjen-bağımsız PC3 prostat kanseri hücrelerinin büyümesini, apoptoz indüksiyonu, MnSOD regülasyonu ve yüksek oksidatif stres gibi süreçler yoluyla inhibe ettiğini göstermektedir.

Ethical Statement

Hücre kültürü üzerinde çalışmalar yapıldığı için etik kabul yazısına gerek yoktur.

Supporting Institution

Bezmialem Vakıf Üniversitesi

Project Number

Project no. 12. 2014/30

References

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca Cancer J Clin. 2021;71:209–249.
  • Chandrasekar T, Yang JC, Gao AC, Evans CP. Mechanisms of resistance in castration-resistant prostate cancer (CRPC). Transl Androl Urol. 2015;4:365-80.
  • Joshi H, Gupta DS, Abjani NK, Kaur G, Mohan CD, Kaur J et al. Genistein: a promising modulator of apoptosis and survival signaling in cancer. Naunyn Schmiedebergs Arch Pharmacol. 2023;396:2893-2910.
  • Sawada N, Iwasaki M, Yamaji T, Shimazu T, Inoue M, Tsugane S. Japan Public Health Center-based Prospective Study Group. Soy and isoflavone consumption and subsequent risk of prostate cancer mortality: the Japan Public Health Center-based Prospective Study. Int J Epidemiol. 2020;49:1553-1561.
  • Sharifi-Rad J, Quispe C, Imran M, Rauf A, Nadeem M, Gondal TA et al. Genistein: an integrative overview of its mode of action, pharmacological properties, and health benefits. Oxid Med Cell Longev. 2021;2021:3268136.
  • Liu Y, Kyle E, Lieberman R, Crowell J, Kellof G, Bergan RC. Focal adhesion kinase (FAK) phosphorylation is not required for genistein-induced FAK-beta-1-integrin complex formation. Clin Exp Metastasis. 2000;18:203-12.
  • Hörmann V, Kumi-Diaka J, Durity M, Rathinavelu A. Anticancer activities of genistein-topotecan combination in prostate cancer cells. J Cell Mol Med. 2012;16:2631-6.
  • Fu Z, Cao X, Liu L, Cao X, Cui Y, Li X et al. Genistein inhibits lung cancer cell stem-like characteristics by modulating MnSOD and FoxM1 expression. Oncol Lett. 2020;20:2506-2515.
  • Rasheed S, Rehman K, Shahid M, Suhail S, Akash MSH. Therapeutic potentials of genistein: New insights and perspectives. J Food Biochem. 2022;46:e14228.
  • Jordaens L, Arias-Alvarez M, Pintelon I, Thys S, Valckx S, Dezhkam Y et al. Elevated non-esterified fatty acid concentrations hamper bovine oviductal epithelial cell physiology in three different in vitro culture systems. Theriogenology. 2015;84:899-910.
  • Wynne S, Djakiew D. NSAID inhibition of prostate cancer cell migration is mediated by Nag-1 Induction via the p38 MAPK-p75(NTR) pathway. Mol Cancer Res. 2010;8:1656-64.
  • Goncu B, Sevgi E, Kizilarslan Hancer C, Gokay G, Ozten N. Differential anti-proliferative and apoptotic effects of lichen species on human prostate carcinoma cells. PLoS One. 2020;15:e0244831.
  • Wang C, Ding K, Xie X, Zhou J, Liu P, Wang S et al. Soy product consumption and the risk of cancer: a systematic review and meta-analysis of observational studies. Nutrients. 2024;16:986.
  • Alorda-Clara M, Torrens-Mas M, Morla-Barcelo PM, Roca P, Sastre-Serra J, Pons DG et al. High concentrations of genistein decrease cell viability depending on oxidative stress and inflammation in colon cancer cell lines. Int J Mol Sci. 2022;23:7526.
  • Borrás C, Gambini J, Gómez-Cabrera MC, Sastre J, Pallardó FV, Mann GE et al. Genistein, a soy isoflavone, up-regulates expression of antioxidant genes: involvement of estrogen receptors, ERK1/2, and NFκB. FASEB J. 2006;20:2136-2138.
  • Terzioglu-Usak S, Yildiz MT, Goncu B, Ozten-Kandas N. Achieving the balance: Biphasic effects of genistein on PC-3 cells. J Food Biochem. 2019;43:e12951.
  • Pavese JM, Farmer RL, Bergan RC. Inhibition of cancer cell invasion and metastasis by genistein. Cancer Metastasis Rev. 2010;29:465-82.
  • Messina M. Impact of soy foods on the development of breast cancer and the prognosis of breast cancer patients. Forsch Komplementmed. 2016;23:75-80.
  • Yang G, Shu XO, Li HL, Chow WH, Wen W, Xiang YB, et al. Prediagnosis soy food consumption and lung cancer survival in women. J Clin Oncol. 2013;31:1548-53.
  • Kumar B, Koul S, Khandrika L, Meacham RB, Koul HK. Oxidative stress is inherent in prostate cancer cells and is required for aggressive phenotype. Cancer Res. 2008;68:1777-85.
  • Tuli HS, Tuorkey MJ, Thakral F, Sak K, Kumar M, Sharma AK et al. Molecular mechanisms of action of genistein in cancer: recent advances. Front Pharmacol. 2019;10:1336

Impact of genistein on androgen-independent PC3 prostate cancer cells

Year 2025, Volume: 50 Issue: 1, 231 - 240, 31.03.2025
https://doi.org/10.17826/cumj.1633575

Abstract

Purpose: This study evaluates genistein’s effects on cell survival, migration, apoptosis, reactive oxygen species (ROS) generation, and Manganese Superoxide Dismutase (MnSOD) expression in androgen-independent PC3 prostate cancer cells, providing insight into its potential as an adjuvant therapy for castration-resistant prostate cancer (CRPC).
Materials and Methods: Cells were treated with vehicle only and 0.5, 2.5, 5, 10, and 50 µM genistein concentrations for 24 and 48 hours. Cell proliferation assay, wound healing assay, ROS measurement, apoptosis detection, and MnSOD protein expression analysis were performed.
Results: The findings indicate a biphasic effect of genistein on PC3 cell survival. Lower to physiologically relevant concentrations (0.5–10 µM) exhibit a modest stimulatory effect, whereas a higher, pharmacologically achievable concentration (50 µM) leads to a time-dependent decline in survival and a significant restriction on migration. In vehicle-treated cells, 77% remained viable, with low early (3.65%) and late apoptosis (16.35%). Lower genistein concentrations (0.5–10 µM) caused a slight increase in apoptosis and a modest decline in viability. However, at 50 µM, only 18.7% of cells remained viable, while 74.25% underwent late apoptosis or cell death.
Conclusion: These findings demonstrate that genistein, particularly at higher concentrations, inhibits androgen-independent PC3 cell growth through apoptosis induction, MnSOD regulation, and elevated oxidative stress.

Ethical Statement

As the study is conducted on the cell line, there is no need for ethical clearance.

Supporting Institution

Bezmialem Vakif University

Project Number

Project no. 12. 2014/30

References

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca Cancer J Clin. 2021;71:209–249.
  • Chandrasekar T, Yang JC, Gao AC, Evans CP. Mechanisms of resistance in castration-resistant prostate cancer (CRPC). Transl Androl Urol. 2015;4:365-80.
  • Joshi H, Gupta DS, Abjani NK, Kaur G, Mohan CD, Kaur J et al. Genistein: a promising modulator of apoptosis and survival signaling in cancer. Naunyn Schmiedebergs Arch Pharmacol. 2023;396:2893-2910.
  • Sawada N, Iwasaki M, Yamaji T, Shimazu T, Inoue M, Tsugane S. Japan Public Health Center-based Prospective Study Group. Soy and isoflavone consumption and subsequent risk of prostate cancer mortality: the Japan Public Health Center-based Prospective Study. Int J Epidemiol. 2020;49:1553-1561.
  • Sharifi-Rad J, Quispe C, Imran M, Rauf A, Nadeem M, Gondal TA et al. Genistein: an integrative overview of its mode of action, pharmacological properties, and health benefits. Oxid Med Cell Longev. 2021;2021:3268136.
  • Liu Y, Kyle E, Lieberman R, Crowell J, Kellof G, Bergan RC. Focal adhesion kinase (FAK) phosphorylation is not required for genistein-induced FAK-beta-1-integrin complex formation. Clin Exp Metastasis. 2000;18:203-12.
  • Hörmann V, Kumi-Diaka J, Durity M, Rathinavelu A. Anticancer activities of genistein-topotecan combination in prostate cancer cells. J Cell Mol Med. 2012;16:2631-6.
  • Fu Z, Cao X, Liu L, Cao X, Cui Y, Li X et al. Genistein inhibits lung cancer cell stem-like characteristics by modulating MnSOD and FoxM1 expression. Oncol Lett. 2020;20:2506-2515.
  • Rasheed S, Rehman K, Shahid M, Suhail S, Akash MSH. Therapeutic potentials of genistein: New insights and perspectives. J Food Biochem. 2022;46:e14228.
  • Jordaens L, Arias-Alvarez M, Pintelon I, Thys S, Valckx S, Dezhkam Y et al. Elevated non-esterified fatty acid concentrations hamper bovine oviductal epithelial cell physiology in three different in vitro culture systems. Theriogenology. 2015;84:899-910.
  • Wynne S, Djakiew D. NSAID inhibition of prostate cancer cell migration is mediated by Nag-1 Induction via the p38 MAPK-p75(NTR) pathway. Mol Cancer Res. 2010;8:1656-64.
  • Goncu B, Sevgi E, Kizilarslan Hancer C, Gokay G, Ozten N. Differential anti-proliferative and apoptotic effects of lichen species on human prostate carcinoma cells. PLoS One. 2020;15:e0244831.
  • Wang C, Ding K, Xie X, Zhou J, Liu P, Wang S et al. Soy product consumption and the risk of cancer: a systematic review and meta-analysis of observational studies. Nutrients. 2024;16:986.
  • Alorda-Clara M, Torrens-Mas M, Morla-Barcelo PM, Roca P, Sastre-Serra J, Pons DG et al. High concentrations of genistein decrease cell viability depending on oxidative stress and inflammation in colon cancer cell lines. Int J Mol Sci. 2022;23:7526.
  • Borrás C, Gambini J, Gómez-Cabrera MC, Sastre J, Pallardó FV, Mann GE et al. Genistein, a soy isoflavone, up-regulates expression of antioxidant genes: involvement of estrogen receptors, ERK1/2, and NFκB. FASEB J. 2006;20:2136-2138.
  • Terzioglu-Usak S, Yildiz MT, Goncu B, Ozten-Kandas N. Achieving the balance: Biphasic effects of genistein on PC-3 cells. J Food Biochem. 2019;43:e12951.
  • Pavese JM, Farmer RL, Bergan RC. Inhibition of cancer cell invasion and metastasis by genistein. Cancer Metastasis Rev. 2010;29:465-82.
  • Messina M. Impact of soy foods on the development of breast cancer and the prognosis of breast cancer patients. Forsch Komplementmed. 2016;23:75-80.
  • Yang G, Shu XO, Li HL, Chow WH, Wen W, Xiang YB, et al. Prediagnosis soy food consumption and lung cancer survival in women. J Clin Oncol. 2013;31:1548-53.
  • Kumar B, Koul S, Khandrika L, Meacham RB, Koul HK. Oxidative stress is inherent in prostate cancer cells and is required for aggressive phenotype. Cancer Res. 2008;68:1777-85.
  • Tuli HS, Tuorkey MJ, Thakral F, Sak K, Kumar M, Sharma AK et al. Molecular mechanisms of action of genistein in cancer: recent advances. Front Pharmacol. 2019;10:1336
There are 21 citations in total.

Details

Primary Language English
Subjects Urology, Cancer Cell Biology
Journal Section Research
Authors

Nur Özten Kandaş 0000-0002-0441-8397

Şule Terzioğlu Uşak 0000-0002-4594-2697

Beyza Göncü 0000-0001-6026-8218

Project Number Project no. 12. 2014/30
Publication Date March 31, 2025
Submission Date February 5, 2025
Acceptance Date March 24, 2025
Published in Issue Year 2025 Volume: 50 Issue: 1

Cite

MLA Özten Kandaş, Nur et al. “Impact of Genistein on Androgen-Independent PC3 Prostate Cancer Cells”. Cukurova Medical Journal, vol. 50, no. 1, 2025, pp. 231-40, doi:10.17826/cumj.1633575.