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Journals / Online Türk Sağlık Bilimleri Dergisi / 2024 / Cilt: 9 Sayı: 1

The Effect of Thymoquinone on the Protein Levels of PLA2G7, UCP2, and NEDD4L Genes Associated with Lipid Droplets Formation in Prostate Cancer

Prostat Kanserinde Lipid Damlacık Oluşumu ile İlişkili PLA2G7, UCP2 ve NEDD4L Genlerinin Protein Seviyeleri Üzerine Timokinonun Etkisi

Abdelhak Hadjmimoune(ANKARA YILDIRIM BEYAZIT ÜNİVERSİTESİ)0000-0001-7525-955X
Ahmet Çarhan(ANKARA YILDIRIM BEYAZIT ÜNİVERSİTESİ)0000-0003-1584-0072
Beyza Ecem Öz Bedir(ANKARA YILDIRIM BEYAZIT ÜNİVERSİTESİ)0000-0002-0596-834X
Hümeyra Yılmaz(ANKARA YILDIRIM BEYAZIT ÜNİVERSİTESİ)0000-0001-7530-4568
Mustafa Emre Ercın(ANKARA YILDIRIM BEYAZIT ÜNİVERSİTESİ)0000-0002-7340-8045
Ender Şimşek(ANKARA YILDIRIM BEYAZIT ÜNİVERSİTESİ)0000-0001-6635-4125
Pages
97–102
Publication Date
2024-03-11
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Further investigations are needed to confirm the efficacy of TQ and explore its potential utility as a therapeutic agent for PCa treatment.

📌 3 Key Takeaways

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Objective & Hypothesis:Objective: Prostate cancer (PCa) patients suffer severe side effects of standard treatment beside the resistance to castration.
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Key Findings & Data:PCa cells shows increased lipogenesis.
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Conclusion & Impact:Further investigations are needed to confirm the efficacy of TQ and explore its potential utility as a therapeutic agent for PCa treatment.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:NEDD4L · PLA2G7 · prostat kanser metabolizması

Abstract

Objective: Prostate cancer (PCa) patients suffer severe side effects of standard treatment beside the resistance to castration. PCa cells shows increased lipogenesis. Thymoquinone (TQ) inhibits cell proliferation, metastasis, and invasion. However, there was no study on the effect of TQ on the levels of NEDDL4, PLA2G7, and UCP2 lipid droplets (LD) related proteins. Hence, the study aims to investigate the impact of TQ on PLA2G7, UCP2, and NEDD4L proteins on DU145 and PC3 cell lines. Materials and Methods: Cells were cultured and treated with TQ with a IC50 of 60 µM and 80 µM for DU145 and PC3, respectively. PLA2G7, UCP2, and NEDD4L levels were measured using the ELISA. Results: TQ has significantly increased the level of NEDD4L (p<0.01 for DU145 and p<0.001 for PC3) and decreased the level of UCP2 proteins (p<0.05). Conclusions: Our preliminary findings suggest that TQ may impact NEDD4L and UCP2, indicating a potential role in repressing LD. Further investigations are needed to confirm the efficacy of TQ and explore its potential utility as a therapeutic agent for PCa treatment.

Özet

Amaç: Prostat kanseri (PCa) hastalarına yönelik standart tedavide, kastrasyona dirençli tipin gelişmesinin yanı sıra ciddi yan etkiler de yaşanmaktadır. PCa hücrelerinin esas olarak artmış lipogenez ile karakterize olduğu bilinmektedir. Timokinonun (TQ) hücre proliferasyonunu, metastazı ve invazyonu inhibe ettiği gösterilmiştir. Ancak literatürde TQ'nun NEDDL4, PLA2G7 ve UCP2 lipit damlacığı ile ilişkili proteinlerin düzeylerine etkisine ilişkin bir çalışma bulunmamaktadır. Bu çalışmanın temel amacı, TQ'nun PLA2G7, UCP2 ve NEDD4L proteinleri üzerindeki DU145 ve PC3 hücre hatları üzerindeki etkisini araştırmaktır. Materyal ve Metot: Hücreler çoğaldı ve DU145 ve PC3 için sırasıyla 60 μM ve 80 μM IC50 ile TQ ile tedavi edildi. İnkübasyondan sonra, PLA2G7, UCP2 ve NEDD4L seviyeleri ELISA yöntemi kullanılarak ölçüldü. Bulgular: TQ, NEDD4L düzeyini önemli ölçüde artırmıştır (DU145 için p<0.01 ve PC3 için p<0.001). Ayrıca, TQ'nun UCP2 protein düzeyini azalttığı da gösterilmiştir (p<0.05). Sonuç: Çalışmamızın başlangıç bulguları, TQ'nun öncelikle NEDD4L ve UCP2 üzerinde etkisi olabileceğini göstermektedir. Bu, TQ'nun LD üzerinde baskılayıcı bir etkiye sahip olabileceğini ve daha fazla araştırma ile PCa tedavisi için faydalı bir molekül olabileceğini öne sürmektedir

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Cite This Article

Hadjmimoune, A., Çarhan, A., Bedir, B. E. Ö., Yılmaz, H., Ercın, M. E., Şimşek, E., *, E. Ş. (2024). The Effect of Thymoquinone on the Protein Levels of PLA2G7, UCP2, and NEDD4L Genes Associated with Lipid Droplets Formation in Prostate Cancer. Online Türk Sağlık Bilimleri Dergisi, Cilt: 9 Sayı: 1, 97–102. https://doi.org/10.26453/otjhs.1422576

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References (30)

  1. Sung H, Ferlay J, Siegel RL, 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(3):209-249. doi:10.3322/caac.21660
  2. Draisma G, Etzioni R, Tsodikov A, et al. Lead time and overdiagnosis in prostate-specific antigen screening: Importance of methods and context. J Natl Cancer Inst. 2009;101(6):374-383. doi:10.1093/jnci/djp001
  3. Lowrance WT, Breau RH, Chou R, et al. Advanced prostate cancer: AUA/ASTRO/SUO guideline part I. J Urol. 2021;205(1):14-21. doi:10.1097/JU.0000000000001375
  4. e Bono JS, Oudard S, Ozguroglu M, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: A randomised open-Label trial. Lancet. 2010;376(9747):1147-1154. doi:10.1016/S0140-6736(10)61389-X
  5. Asaduzzaman Khan M, Tania M, Fu S, Fu J. Thymoquinone, as an anticancer molecule: From basic research to clinical investigation. oncotarget. 2017;8(31):51907-51919. doi:10.18632/oncotarget.17206
  6. Dirican A, Atmaca H, Bozkurt E, Erten C, Karaca B, Uslu R. Novel Combination of docetaxel and thymoquinone induces synergistic cytotoxicity and apoptosis in Du-145 human prostate cancer cells by modulating pı3k-Akt pathway. Clin Transl Oncol. 2015;17(2):145-151. doi:10.1007/s12094-014-1206-6
  7. Scaglia N, Frontini-López YR, Zadra G. Prostate cancer progression: as a matter of fats. Front Oncol. 2021;11:719865. doi:10.3389/fonc.2021.719865
  8. Nardi F, Fitchev P, Brooks KM, et al. Lipid droplet velocity is a microenvironmental sensor of aggressive tumors regulated by v-Atpase and PEDF. Lab Invest. 2019;99(12):1822-1834. doi:10.1038/s41374-019-0296-8
  9. Guijas C, Rodríguez JP, Rubio JM, Balboa MA, Balsinde J. Phospholipase A2 regulation of lipid droplet formation. Biochim Biophys Acta. 2014;1841(12):1661-1671. doi:10.1016/j.bbalip.2014.10.004
  10. Aguilar E, Esteves P, Sancerni T, et al. UCP2 Deficiency Increases colon tumorigenesis by promoting lipid synthesis and depleting NADPH for antioxidant defenses. Cell Rep. 2019;28(9):2306-2316.e5. doi:10.1016/j.celrep.2019.07.097
  11. Hu XY, Xu YM, Fu Q, Yu JJ, Huang J. Nedd4L Expression is downregulated in prostate cancer compared to benign prostatic hyperplasia. Eur J Surg Oncol. 2009;35(5):527-531. doi:10.1016/j.ejso.2008.09.015
  12. Hooper C, Puttamadappa SS, Loring Z, Shekhtman A, Bakowska JC. Spartin Activates atrophin-1-interacting protein 4 (AIP4) E3 ubiquitin ligase and promotes ubiquitination of adipophilin on lipid droplets. BMC Biol. 2010;8:72. doi:10.1186/1741-7007-8-72
  13. Bermúdez MA, Balboa MA, Balsinde J. Lipid Droplets, Phospholipase A2, arachidonic acid, and atherosclerosis. Biomedicines. 2021;9(12):1891. doi:10.3390/biomedicines9121891
  14. Alberts P, Rotin D. Regulation of lipid droplet turnover by ubiquitin ligases. BMC Biol. 2010;8:94. doi:10.1186/1741-7007-8-94
  15. Kou B, Liu W, Zhao W, et al. Thymoquinone inhibits epithelial-mesenchymal transition in prostate cancer cells by negatively regulating the TGF-Β/Smad2/3 signaling pathway. Oncol Rep. 2017;38(6):3592-3598. doi:10.3892/or.2017.6012
  16. Nguyen, S., Nguyen, H., & Truong, K. Comparative cytotoxic effects of methanol, ethanol and DMSO on human cancer cell cines. Biomedical Research And Therapy. 2020;7(7):3855-3859. doi.org/10.15419/bmrat.v7i7.614
  17. Kimmelman AC. Metabolic dependencies in RAS-driven cancers. Clin Cancer Res. 2015;21(8):1828-1834. doi:10.1158/1078-0432.CCR-14-2425
  18. Datta D, Aftabuddin M, Gupta DK, Raha S, Sen P. Human prostate cancer hallmarks map. Sci Rep. 2016;6:30691. doi:10.1038/srep30691
  19. Wu X, Daniels G, Lee P, Monaco ME. Lipid metabolism in prostate cancer. Am J Clin Exp Urol. 2014;2(2):111-120.
  20. Butler LM, Perone Y, Dehairs J, et al. Lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention. Adv Drug Deliv Rev. 2020;159:245-293. doi:10.1016/j.addr.2020.07.013
  21. Butler LM, Perone Y, Dehairs J, et al. Lipids and cancer: emerging roles in pathogenesis, diagnosis and therapeutic intervention. Adv Drug Deliv Rev. 2020;159:245-293. doi:10.1016/j.addr.2020.07.013
  22. van Bokhoven A, Varella-Garcia M, Korch C, et al. Molecular characterization of human prostate carcinoma cell lines. Prostate. 2003;57(3):205-225. doi:10.1002/pros.10290
  23. Sun B, Zhang X, Talathi S, Cummings BS. Inhibition of Ca2+-independent phospholipase A2 decreases prostate cancer cell growth by P53-dependent and independent mechanisms. J Pharmacol Exp Ther. 2008;326(1):59-68. doi:10.1124/jpet.108.138958
  24. Patel MI, Singh J, Niknami M, et al. Cytosolic phospholipase A2-alpha: A potential therapeutic target for prostate cancer. Clin Cancer Res. 2008;14(24):8070-8079. doi:10.1158/1078-0432.CCR-08-0566
  25. Cho YS. Genipin, an inhibitor of UCP2 as a promising new anticancer agent: A review of the literature. Int J Mol Sci. 2022;23(10):5637. doi:10.3390/ijms23105637
  26. Yu J, Shi L, Lin W, Lu B, Zhao Y. UCP2 promotes proliferation and chemoresistance through regulating the NF-Κb/Β-catenin axis and mitochondrial ROS in gallbladder cancer. Biochem Pharmacol. 2020;172:113745. doi:10.1016/j.bcp.2019.113745
  27. Hua J, Zhang Z, Zhang L, Sun Y, Yuan Y. UCP-2 Inhibitor enhanced the efficacy of trastuzumab against HER2 positive breast cancer cells. Cancer Chemother Pharmacol. 2021;88(4):633-642. doi:10.1007/s00280-021-04303-4
  28. ERCIN ME, ŞİMŞEK E. Programming of energy metabolism in prostate carcinoma: In silico analysis. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi. 2021;9(4):350-356. doi:10.37989/gumussagbil.797335
  29. Huang X, Chen J, Cao W, et al. The many substrates and functions of NEDD4-1. Cell Death Dis. 2019;10(12):904. doi:10.1038/s41419-019-2142-8
  30. Qian W, Yu D, Zhang J, et al. Wogonin attenuates isoprenaline-induced myocardial hypertrophy in mice by suppressing the PI3K/Akt pathway. Front Pharmacol. 2018;9:896. doi:10.3389/fphar.2018.00896