Targeting Crosstalk Between Nrf-2, NF-κB and Androgen Receptor Signaling in Prostate Cancer

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2018 Sep 28

PMID 30257470

Citations 35

Authors

Namrata Khurana

Suresh C Sikka

Affiliations

Soon will be listed here.

Abstract

Oxidative stress, inflammation and androgen receptor (AR) signaling play a pivotal role in the initiation, development and progression of prostate cancer (PCa). Numerous papers in the literature have documented the interconnection between oxidative stress and inflammation; and how antioxidants can combat the inflammation. It has been shown in the literature that both oxidative stress and inflammation regulate AR, the key receptor involved in the transition of PCa to castration resistant prostate cancer (CRPC). In this review, we discuss about the importance of targeting Nrf-2-antioxidant signaling, NF-κB inflammatory response and AR signaling in PCa. Finally, we discuss about the crosstalk between these three critical pathways as well as how the anti-inflammatory antioxidant phytochemicals like sulforaphane (SFN) and curcumin (CUR), which can also target AR, can be ideal candidates in the chemoprevention of PCa.

Citing Articles

Synergistic Strategies for Castration-Resistant Prostate Cancer: Targeting AR-V7, Exploring Natural Compounds, and Optimizing FDA-Approved Therapies.

Rahman M, Akter K, Ahmed K, Maharub Hossain Fahim M, Aktary N, Park M Cancers (Basel). 2024; 16(16).

PMID: 39199550 PMC: 11352813. DOI: 10.3390/cancers16162777.

Prognostic relevance and validation of ARPC1A in the progression of low-grade glioma.

Dai J, Gao J, Dong H Aging (Albany NY). 2024; 16(14):11162-11184.

PMID: 39012280 PMC: 11315382. DOI: 10.18632/aging.205952.

The Growth Inhibitory Effect of Resveratrol and Gallic Acid on Prostate Cancer Cell Lines through the Alteration of Oxidative Stress Balance: The Interplay between , and Genes.

Moghadam D, Zarei R, Rostami A, Samare-Najaf M, Ghojoghi R, Savardashtaki A Anticancer Agents Med Chem. 2024; 24(16):1220-1232.

PMID: 38984567 DOI: 10.2174/0118715206317999240708062744.

Structure based docking and biological evaluation towards exploring potential anti-cancerous and apoptotic activity of 6-Gingerol against human prostate carcinoma cells.

Khan H, Azad I, Arif Z, Parveen S, Kumar S, Rais J BMC Complement Med Ther. 2024; 24(1):8.

PMID: 38166796 PMC: 10759763. DOI: 10.1186/s12906-023-04269-1.

Bunge Ameliorates Benign Prostatic Hyperplasia through Regulation of Oxidative Stress via Nrf-2/HO-1 Activation.

Choi Y, Wedamulla N, Kim S, Oh M, Seo K, Han J J Microbiol Biotechnol. 2023; 34(5):1059-1072.

PMID: 37994101 PMC: 11180924. DOI: 10.4014/jmb.2308.08053.

References

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014; 136(5):E359-86. DOI: 10.1002/ijc.29210. View

JACOBS M, Harrison S . Structure of an IkappaBalpha/NF-kappaB complex. Cell. 1998; 95(6):749-58. DOI: 10.1016/s0092-8674(00)81698-0. View

Schultz M, Hagan S, Datta A, Zhang Y, Freeman M, Sikka S . Nrf1 and Nrf2 transcription factors regulate androgen receptor transactivation in prostate cancer cells. PLoS One. 2014; 9(1):e87204. PMC: 3899380. DOI: 10.1371/journal.pone.0087204. View

Dakubo G, Parr R, Costello L, Franklin R, Thayer R . Altered metabolism and mitochondrial genome in prostate cancer. J Clin Pathol. 2006; 59(1):10-6. PMC: 1860255. DOI: 10.1136/jcp.2005.027664. View

Ahmed S, Luo L, Namani A, Wang X, Tang X . Nrf2 signaling pathway: Pivotal roles in inflammation. Biochim Biophys Acta Mol Basis Dis. 2016; 1863(2):585-597. DOI: 10.1016/j.bbadis.2016.11.005. View

Suzuki H, Ueda T, Ichikawa T, Ito H . Androgen receptor involvement in the progression of prostate cancer. Endocr Relat Cancer. 2003; 10(2):209-16. DOI: 10.1677/erc.0.0100209. View

Jin R, Yi Y, Yull F, Blackwell T, Clark P, Koyama T . NF-κB gene signature predicts prostate cancer progression. Cancer Res. 2014; 74(10):2763-72. PMC: 4024337. DOI: 10.1158/0008-5472.CAN-13-2543. View

Soares M, Seldon M, Gregoire I, Vassilevskaia T, Berberat P, Yu J . Heme oxygenase-1 modulates the expression of adhesion molecules associated with endothelial cell activation. J Immunol. 2004; 172(6):3553-63. DOI: 10.4049/jimmunol.172.6.3553. View

Li W, Khor T, Xu C, Shen G, Jeong W, Yu S . Activation of Nrf2-antioxidant signaling attenuates NFkappaB-inflammatory response and elicits apoptosis. Biochem Pharmacol. 2008; 76(11):1485-9. PMC: 2610259. DOI: 10.1016/j.bcp.2008.07.017. View

10.

Gibbs A, Schwartzman J, Deng V, Alumkal J . Sulforaphane destabilizes the androgen receptor in prostate cancer cells by inactivating histone deacetylase 6. Proc Natl Acad Sci U S A. 2009; 106(39):16663-8. PMC: 2757849. DOI: 10.1073/pnas.0908908106. View

11.

Pelicano H, Carney D, Huang P . ROS stress in cancer cells and therapeutic implications. Drug Resist Updat. 2004; 7(2):97-110. DOI: 10.1016/j.drup.2004.01.004. View

12.

Kwon O, Kim K, Kim S, Ha R, Oh W, Kim M . NF-kappaB inhibition increases chemosensitivity to trichostatin A-induced cell death of Ki-Ras-transformed human prostate epithelial cells. Carcinogenesis. 2006; 27(11):2258-68. DOI: 10.1093/carcin/bgl097. View

13.

Cheung P, Woolcock B, Adomat H, Sutcliffe M, Bainbridge T, Jones E . Protein profiling of microdissected prostate tissue links growth differentiation factor 15 to prostate carcinogenesis. Cancer Res. 2004; 64(17):5929-33. DOI: 10.1158/0008-5472.CAN-04-1216. View

14.

Storka A, Vcelar B, Klickovic U, Gouya G, Weisshaar S, Aschauer S . Safety, tolerability and pharmacokinetics of liposomal curcumin in healthy humans. Int J Clin Pharmacol Ther. 2014; 53(1):54-65. DOI: 10.5414/CP202076. View

15.

Xu C, Shen G, Chen C, Gelinas C, Kong A . Suppression of NF-kappaB and NF-kappaB-regulated gene expression by sulforaphane and PEITC through IkappaBalpha, IKK pathway in human prostate cancer PC-3 cells. Oncogene. 2005; 24(28):4486-95. DOI: 10.1038/sj.onc.1208656. View

16.

Choi S, Lew K, Xiao H, Herman-Antosiewicz A, Xiao D, Brown C . D,L-Sulforaphane-induced cell death in human prostate cancer cells is regulated by inhibitor of apoptosis family proteins and Apaf-1. Carcinogenesis. 2006; 28(1):151-62. DOI: 10.1093/carcin/bgl144. View

17.

Wu Z, Yuan Y, Geng H, Xia S . Influence of immune inflammation on androgen receptor expression in benign prostatic hyperplasia tissue. Asian J Androl. 2011; 14(2):316-9. PMC: 3735085. DOI: 10.1038/aja.2011.154. View

18.

Martin K, Barrett J . Reactive oxygen species as double-edged swords in cellular processes: low-dose cell signaling versus high-dose toxicity. Hum Exp Toxicol. 2002; 21(2):71-5. DOI: 10.1191/0960327102ht213oa. View

19.

Keum Y, Khor T, Lin W, Shen G, Kwon K, Barve A . Pharmacokinetics and pharmacodynamics of broccoli sprouts on the suppression of prostate cancer in transgenic adenocarcinoma of mouse prostate (TRAMP) mice: implication of induction of Nrf2, HO-1 and apoptosis and the suppression of Akt-dependent.... Pharm Res. 2009; 26(10):2324-31. DOI: 10.1007/s11095-009-9948-5. View

20.

Khurana N, Kim H, Chandra P, Talwar S, Sharma P, Abdel-Mageed A . Multimodal actions of the phytochemical sulforaphane suppress both AR and AR-V7 in 22Rv1 cells: Advocating a potent pharmaceutical combination against castration-resistant prostate cancer. Oncol Rep. 2017; 38(5):2774-2786. PMC: 5780030. DOI: 10.3892/or.2017.5932. View