Effects of IL-6 and TNF-α Cytokines on Cell Proliferation in Androgen Dependent/Independent Prostate Cancer Cell Lines

Year 2024, , 1 - 8, 15.03.2024

Serhad Onat , Sümeyye Aydoğan Türkoğlu , Feray Köçkar

https://doi.org/10.28979/jarnas.1282119

Abstract

Prostate cancer is the second most common types of cancer among men worldwide. Prostate cancer, caused by abnormal and uncontrolled growth of the cells that make up the prostate tissue, is second only to related deaths in men. Cytokines, which have a significant impact on the response of the immune system, play an active role in the development of prostate cancer. This study determined the effect of proinflammatory cytokines, IL-6 and TNF-α on the proliferation of prostate cancer (PCα) cell lines. MTT test was used for the effect of cytokines applied at different doses and hours on cell viability. According to our results, IL-6 cytokine caused a high increase in proliferation in androgen-dependent LNCaP cells, while androgen-independent PC-3 cells showed different proliferative effects in time and dose-dependent manner. TNF-α cytokine had a negative effect on the proliferation of androgen-dependent LNCaP cells, while it increased the proliferation level of androgen-independent PC-3 cells. These results show that the effects of cell lines-on the proliferation of cells are different depending on their androgen sensitivity, which will be used in different cytokinetic studies to determine the inflammatory response to treat prostate cancer. It is especially important to consider this condition during the advancement of prostate cancer treatment strategies.

Keywords

Cytokine, IL-6, prostate cancer, proliferation, TNF-α

References

• M. Daniyal, Z. A. Siddiqui, M. Akram, H. M. Asif, S. Sultana, A. Khan, Epidemiology, etiology, diagnosis and treatment of prostate cancer, Asian Pacific Journal of Cancer Prevention: APJCP 15 (22) (2014) 9575–9578.
• S. Sandhu, C. M. Moore, E. Chiong, H. Beltran, R. G. Bristow, S. G. Williams, Prostate cancer. The Lancet 398 (10305) (2021) 1075–1090.
• B. J. Feldman, D. Feldman, The development of androgen-independent prostate cancer, Nature Reviews Cancer 1 (1) (2001) 34–45.
• M. M. Shen, C. Abate-Shen, Molecular genetics of prostate cancer: New prospects for old challenges, Genes & Development 24 (18) (2010) 1967–2000.
• T. Karantanos, P. G. Corn, T. C. Thompson, Prostate cancer progression after androgen deprivation therapy: Mechanisms of castrate resistance and novel therapeutic approaches, Oncogene 32 (49) (2013) 5501–5511.
• T. O. Adekoya, R. M. Richardson, Cytokines and chemokines as mediators of prostate cancer metastasis, International Journal of Molecular Sciences 21 (12) (2020) Article Number 4449 29 pages.
• C. B. Siegall, G. Schwab, R. P. Nordan, D. J. FitzGerald, I. Pastan, Expression of the interleukin 6 receptor and interleukin 6 in prostate carcinoma cells, Cancer Research 50 (24) (1990) 7786–7788.
• F. Balkwill, Tumour necrosis factor and cancer, Nature Reviews Cancer 9 (5) (2009) 361–371.
• H. Wang, R. Fang, X. F. Wang, F. Zhang, D. Y. Chen, B. Zhou, H. S. Wang, S. H. Cai, J. Du, Stabilization of Snail through AKT/GSK-3β signaling pathway is required for TNF-α-induced epithelial-mesenchymal transition in prostate cancer PC3 cells, European Journal of Pharmacology 714 (1-3) (2013) 48–55.
• V. Michalaki, K. Syrigos, P. Charles, J. Waxman, Serum levels of IL-6 and TNF-alpha correlate with clinicopathological features and patient survival in patients with prostate cancer, British Journal of Cancer 90 (12) (2004) 2312–2316.
• R. Nader, J. E. Amm, J. B. Aragon-Ching, Role of chemotherapy in prostate cancer, Asian Journal of Andrology 20 (3) (2018) 221–229.
• J. Zhou, H. Chen, Y. Wu, B. Shi, J. Ding, J. Qi, Plasma IL-6 and TNF-α levels correlate significantly with grading changes in localized prostate cancer, Prostate 82 (5) (2022) 531–539.
• S. A. Türkoğlu, F. Koçkar, SP1 and USF differentially regulate ADAMTS1 gene expression un-der normoxic and hypoxic conditions in hepatoma cells, Gene 575 (1) (2016) 48–57.
• E. Tokay, R. I. Sağkan, F. Koçkar, TNF-α induces URG-4/URGCP gene expression in hepatoma cells through starvation dependent manner, Biochemical Genetics 59 (1) (2021) 300–314.
• N. Hacıoğlu, T. Güngör, E. Tokay, F. C. Önder, M. Ay, F. Köçkar, Synthesis and biological evaluation of 2,4,6-trinitroaniline derivatives as potent antitumor agents, Monatshefte für Chemie-Chemical Monthly 151 (10) (2020) 1629–164.
• M. T. Spiotto, T. D. Chung, STAT3 mediates IL-6-induced neuroendocrine differentiation in prostate cancer cells, The Prostate 42 (3) (2000) 186–195.
• Z. Culig, M. Puhr, Interleukin-6: A multifunctional targetable cytokine in human prostate cancer, Molecular and Cellular Endocrinology 360 (1-2) (2012) 52–58.
• C. Hacıoğlu, S. Kaçar, F. Kar, G. Kanbak, V. Şahintürk, Concentration-dependent effects of zinc sulfate on DU-145 human prostate cancer cell line: Oxidative, apoptotic, inflammatory, and morphological analyzes, Biological Trace Element Research 195 (2) (2020) 436–444.
• F. Kar, C. Hacıoğlu, S. Kaçar, V. Şahintürk, G. Kanbak, Betaine suppresses cell proliferation by increasing oxidative stress-mediated apoptosis and inflammation in DU-145 human prostate cancer cell line, Cell Stress Chaperones 24 (5) (2019) 871-881.
• T. Chen, L. H. Wang, W. L. Farrar, Interleukin 6 activates androgen receptor-mediated gene expression through a signal transducer and activator of transcription 3-dependent pathway in LNCaP prostate cancer cells, Cancer Research 60 (8) (2000) 2132–2135.
• D. Giri, M. Özen, M. Ittmann, Interleukin-6 is an autocrine growth factor in human prostate cancer, The American Journal of Pathology 159 (6) (2001) 2159–2165.
• N. Craft, Y. Shostak, M. Carey, C. L. Sawyers, A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase, Nature Medicine 5 (3) (1999) 280–285.
• K. Jennbacken, T. Tesan, W. Wang, H. Gustavsson, J. E. Damber, K. Welén, N-cadherin inc-reases after androgen deprivation and is associated with metastasis in prostate cancer, Endocrine-Related Cancer 17 (2) (2010) 469–479.
• Z. Culig, G. Bartsch, A. Hobisch, Interleukin-6 regulates androgen receptor activity and prostate cancer cell growth, Molecular and Cellular Endocrinology 197 (1-2) (2002) 231–238.
• F. R. Santer, K. Malinowska, Z. Culig, I. T. Cavarretta, Interleukin-6 trans-signalling differentially regulates proliferation, migration, adhesion and maspin expression in human prostate cancer cells, Endocrine-Related Cancer 17 (1) (2010) 241–253.
• W. Lou, Z. Ni, K. Dyer, D. J. Tweardy, A. C. Gao, Interleukin-6 induces prostate cancer cell growth accompanied by activation of stat3 signaling pathway, The Prostate 42 (3) (2000) 239–242.
• G. Rodríguez-Berriguete, B. Fraile, R. Paniagua, P. Aller, M. Royuela, Expression of NF-κB-related proteins and their modulation during TNF-α-provoked apoptosis in prostate cancer cells, The Prostate 72 (1) (2012) 40–50.
• S. Harada, E. T. Keller, N. Fujimoto, K. Koshida, M. Namiki, T. Matsumoto, A. Mizokami, Long-term exposure of tumor necrosis factor alpha causes hypersensitivity to androgen and anti-androgen withdrawal phenomenon in LNCaP prostate cancer cells, The Prostate 46 (4) (2001) 319–326.
• Y. Nakajima, A. M. DelliPizzi, C. Mallouh, N. R. Ferreri, TNF-mediated cytotoxicity and resistance in human prostate cancer cell lines, The Prostate 29 (5) (1996) 296–302.
• D. Yu, Y. Zhong, X. Li, Y. Li, X. Li, J. Cao, H. Fan, Y. Yuan, Z. Ji, B. Qiao, J.-G. Wen, M. Zhang, G. Kvalheim, J. M. Nesland, Z. Suo, ILs-3, 6 and 11 increase, but ILs-10 and 24 decrease stemness of human prostate cancer cells in vitro, Oncotarget 6 (40) (2015) 42687–42703.
• H. G. Van der Poel, Androgen receptor and TGFbeta1/Smad signaling are mutually inhibitory in prostate cancer, European Urology 48 (6) (2005) 1051–1058.
• A. Mizokami, A. Gotoh, H. Yamada, E. T. Keller, T. Matsumoto, Tumor necrosis factor-alpha represses androgen sensitivity in the LNCaP prostate cancer cell line, The Journal of Urology 164 (3) (2000) 800–805.
• P. C. Smith, A. Hobisch, D. L. Lin, Z. Culig, E. T. Keller, Interleukin-6 and prostate cancer progression, Cytokine & Growth Factor Reviews 12 (1) (2001) 33–40.