Volume 10, Issue 1 (Vol.10 No.1 Apr 2021)                   rbmb.net 2021, 10(1): 69-75 | Back to browse issues page

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Mousavi N, Rahimi S, Yavari S, Kazemi A H, Mohammad Taghi Kashi R, Heidarian R et al . The Effect of Quercetin Nanosuspension on Prostate Cancer Cell Line LNCaP via Hedgehog Signaling Pathway. rbmb.net. 2021; 10 (1) :69-75
URL: http://rbmb.net/article-1-581-en.html
Department of Genetic, Tonekabon Branch, Islamic Azad University, Tehran, Iran.
Abstract:   (827 Views)
Background: Prostate cancer (PCa) is the second leading cause of cancer death in American population. In this manner, novel therapeutic approaches for identification of therapeutic targets for PCa has significant clinical implications. Quercetin is a potent cancer therapeutic agent and dietary antioxidant present in fruit and vegetables.

Methods: To investigate the underlying mechanism by which the PCa was regulated, nanoparticles of quercetin were administrated to cells. For in vitro experiments, human PCa cell line LNCaP were involved. Cell viability assay and quantitative RT-PCR (qRT-PCR) for hedgehog signaling pathway genes were used to determine the key signaling pathway regulated for PCa progression.

Results: The cell viability gradually decreased with increased concentration of quercetin nanoparticles. At 48 h, 40 mM concentration of quercetin treatment showed near 50% of viable cells. Quercetin nanoparticles upregulates Su(Fu) mRNA expressions and downregulates gli mRNA expressions in the LNCaP cells.

Conclusions: The results showed that the hedgehog signaling targeted inhibition may have important implications of PCa therapeutics. Additionally, the outcomes provided new mechanistic basis for further examination of quercetin nanoparticles to discover potential treatment strategies and new targets for PCa inhibition.
Full-Text [PDF 277 kb]   (316 Downloads)    
Type of Article: Original Article | Subject: Molecular Biology
Received: 2020/09/30 | Accepted: 2020/10/13 | Published: 2021/05/9

1. Ward AB, Mir H, Kapur N, Gales DN, Carriere PP, Singh S. Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways. World J Surg Oncol. 2018;16(1):108. [DOI:10.1186/s12957-018-1400-z] [PMID] [PMCID]
2. Hosseini MS, Hosseini F, Ahmadi A, Mozafari M, Amjadi I. Antiproliferative Activity of Hypericum perforatum, Achillea millefolium, and Aloe vera in Interaction with the Prostatic Activity of CD82. Rep Biochem Mol Biol. 2019;8(3):260-268.
3. Taipale J, Beachy PA. The Hedgehog and Wnt signalling pathways in cancer. Nature. 2001;411(6835):349-54. [DOI:10.1038/35077219] [PMID]
4. Sheng T, Li C, Zhang X, Chi S, He N, Chen K, et al. Activation of the hedgehog pathway in advanced prostate cancer. Mol Cancer. 2004;3:29. [DOI:10.1186/1476-4598-3-29] [PMID] [PMCID]
5. Leube B, Drechsler M, Muhlmann K, Schafer R, Schulz WA, Santourlidis S, et al. Refined mapping of allele loss at chromosome 10q23-26 in prostate cancer. Prostate. 2002;50(3):135-44. [DOI:10.1002/pros.10038] [PMID]
6. Berman DM, Desai N, Wang X, Karhadkar SS, Reynon M, Abate-Shen C, et al. Roles for Hedgehog signaling in androgen production and prostate ductal morphogenesis. Dev Biol. 2004;267(2):387-98. [DOI:10.1016/j.ydbio.2003.11.018] [PMID]
7. Wang BE, Shou J, Ross S, Koeppen H, De Sauvage FJ, Gao WQ. Inhibition of epithelial ductal branching in the prostate by sonic hedgehog is indirectly mediated by stromal cells. J Biol Chem. 2003;278(20):18506-13. [DOI:10.1074/jbc.M300968200] [PMID]
8. Ślusarz A, Shenouda NS, Sakla MS, Drenkhahn SK, Narula AS, MacDonald RS, et al. Common botanical compounds inhibit the hedgehog signaling pathway in prostate cancer. Cancer Res. 2010;70(8):3382-90. [DOI:10.1158/0008-5472.CAN-09-3012] [PMID]
9. Senthilkumar K, Arunkumar R, Elumalai P, Sharmila G, Gunadharini DN, Banudevi S, et al. Quercetin inhibits invasion, migration and signalling molecules involved in cell survival and proliferation of prostate cancer cell line (PC‐3). Cell Biochem Funct. 2011;29(2):87-95. [DOI:10.1002/cbf.1725] [PMID]
10. Xing N, Chen Y, Mitchell SH, Young CY. Quercetin inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells. Carcinogenesis. 2001;22(3):409-14. [DOI:10.1093/carcin/22.3.409] [PMID]
11. Bhattacharyya SS, Paul S, De A, Das D, Samadder A, Boujedaini N, et al. Poly (lactide-co-glycolide) acid nanoencapsulation of a synthetic coumarin: cytotoxicity and bio-distribution in mice, in cancer cell line and interaction with calf thymus DNA as target. Toxicol Appl Pharmacol. 2011;253(3):270-81. [DOI:10.1016/j.taap.2011.04.010] [PMID]
12. Maitland ML, Schilsky RL. Clinical trials in the era of personalized oncology. CA Cancer J Clin. 2011;61(6):365-81. [DOI:10.3322/caac.20135] [PMID] [PMCID]
13. Hashemzaei M, Delarami Far A, Yari A, Heravi RE, Tabrizian K, Taghdisi SM, et al. Anticancer and apoptosis‑inducing effects of quercetin in vitro and in vivo. Oncol Rep. 2017;38(2):819-828. [DOI:10.3892/or.2017.5766] [PMID] [PMCID]
14. Bandyopadhyay S, Romero JR, Chattopadhyay N. Kaempferol and quercetin stimulate granulocyte-macrophage colony-stimulating factor secretion in human prostate cancer cells. Mol Cell Endocrinol. 2008;287(1-2):57-64. [DOI:10.1016/j.mce.2008.01.015] [PMID]
15. Azarian M, Amani A, Faramarzi MA, Divsalar A, Eidi A. Design and optimization of noscapine nanosuspensions and study of its cytotoxic effect. J Biomol Struct Dyn. 2019;37(1):147-55. [DOI:10.1080/07391102.2017.1420490] [PMID]
16. Tsao R. Chemistry and biochemistry of dietary polyphenols. Nutrients. 2010;2(12):1231-46. [DOI:10.3390/nu2121231] [PMID] [PMCID]
17. Dong Ys, Wang Jl, Feng Dy, Qin Hz, Wen H, Yin Zm, et al. Protective effect of quercetin against oxidative stress and brain edema in an experimental rat model of subarachnoid hemorrhage. Int J Med Sci. 2014;11(3):282-90. [DOI:10.7150/ijms.7634] [PMID] [PMCID]
18. Kobori M, Takahashi Y, Sakurai M, Akimoto Y, Tsushida T, Oike H, et al. Quercetin suppresses immune cell accumulation and improves mitochondrial gene expression in adipose tissue of diet‐induced obese mice. Mol Nutr Food Res. 2016;60(2):300-12. [DOI:10.1002/mnfr.201500595] [PMID] [PMCID]
19. Shoskes DA, Manickam K. Herbal and complementary medicine in chronic prostatitis. World J Urol. 2003;21(2):109-13. [DOI:10.1007/s00345-003-0332-5] [PMID]
20. Sandhu JS. Prostate cancer and chronic prostatitis. Curr Urol Rep. 2008;9(4):328-32. [DOI:10.1007/s11934-008-0056-6] [PMID]
21. Iyer AK, Khaled G, Fang J, Maeda H. Exploiting the enhanced permeability and retention effect for tumor targeting. Drug discovery today. 2006;11(17-18):812-818. [DOI:10.1016/j.drudis.2006.07.005] [PMID]
22. Cho HJ, Yoon HY, Koo H, Ko SH, Shim JS, Lee JH, et al. Self-assembled nanoparticles based on hyaluronic acid-ceramide (HA-CE) and Pluronic® for tumor-targeted delivery of docetaxel. Biomaterials. 2011;32(29):7181-90. [DOI:10.1016/j.biomaterials.2011.06.028] [PMID]
23. Sharma Vijay K, Mishra D, Sharma A, Srivastava B. Liposomes: present prospective and future challenges. International Journal of Current Pharmaceutical Review & Research. 2010;1(2):6-16.
24. Sanchez P, Hernández AM, Stecca B, Kahler AJ, DeGueme AM, Barrett A, et al. Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling. Proc Natl Acad Sci U S A. 2004;101(34):12561-6. [DOI:10.1073/pnas.0404956101] [PMID] [PMCID]
25. Karhadkar SS, Bova GS, Abdallah N, Dhara S, Gardner D, Maitra A, et al. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature. 2004;431(7009):707-12. [DOI:10.1038/nature02962] [PMID]
26. Ross RK, Pike MC, Coetzee GA, Reichardt JK, Mimi CY, Feigelson H, et al. Androgen metabolism and prostate cancer: establishing a model of genetic susceptibility. Cancer Res. 1998;58(20):4497-504.
27. Huang Y, Jiang X, Liang X, Jiang G. Molecular and cellular mechanisms of castration resistant prostate cancer. Oncol Lett. 2018;15(5):6063-6076. [DOI:10.3892/ol.2018.8123] [PMID] [PMCID]
28. Denis LJ, Griffiths K. Endocrine treatment in prostate cancer. Semin Surg Oncol. 2000;18(1)52-74. https://doi.org/10.1002/(SICI)1098-2388(200001/02)18:1<52::AID-SSU8>3.0.CO;2-6 [DOI:10.1002/(SICI)1098-2388(200001/02)18:13.0.CO;2-6]
29. Priyadarsini RV, Murugan RS, Maitreyi S, Ramalingam K, Karunagaran D, Nagini S. The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-κB inhibition. Eur J Pharmacol. 2010;649(1-3):84-91. [DOI:10.1016/j.ejphar.2010.09.020] [PMID]
30. Chan ST, Yang NC, Huang CS, Liao JW, Yeh SL. Quercetin enhances the antitumor activity of trichostatin A through upregulation of p53 protein expression in vitro and in vivo. PLoS One. 2013;8(1):e54255. [DOI:10.1371/journal.pone.0054255] [PMID] [PMCID]
31. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. cell. 2011;144(5):646-74. [DOI:10.1016/j.cell.2011.02.013] [PMID]
32. Senthilkumar K, Elumalai P, Arunkumar R, Banudevi S, Gunadharini ND, Sharmila G, et al. Quercetin regulates insulin like growth factor signaling and induces intrinsic and extrinsic pathway mediated apoptosis in androgen independent prostate cancer cells (PC-3). Mol Cell Biochem. 2010;344(1-2):173-84. [DOI:10.1007/s11010-010-0540-4] [PMID]
33. Yuan H, Young CY, Tian Y, Liu Z, Zhang M, Lou H. Suppression of the androgen receptor function by quercetin through protein-protein interactions of Sp1, c-Jun, and the androgen receptor in human prostate cancer cells. Mol Cell Biochem. 2010;339(1-2):253-62. [DOI:10.1007/s11010-010-0388-7] [PMID]
34. Yue S, Chen Y, Cheng S. Hedgehog signaling promotes the degradation of tumor suppressor Sufu through the ubiquitin-proteasome pathway. Oncogene. 2009;28(4):492-9. [DOI:10.1038/onc.2008.403] [PMID]

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