Combination of quercetin and hyperoside inhibits prostate cancer cell growth and metastasis via regulation of microRNA‑21

Yang,Feng‑Qiang; Liu,Min; Li,Wei; Che,Jian‑Ping; Wang,Guang‑Chun; Zheng,Jun‑Hua

doi:10.3892/mmr.2014.2813

Combination of quercetin and hyperoside inhibits prostate cancer cell growth and metastasis via regulation of microRNA‑21

Authors:
- Feng‑Qiang Yang
- Min Liu
- Wei Li
- Jian‑Ping Che
- Guang‑Chun Wang
- Jun‑Hua Zheng
View Affiliations

Affiliations: Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, P.R. China
Published online on: October 29, 2014 https://doi.org/10.3892/mmr.2014.2813
Pages: 1085-1092

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Previous studies have reported that hyperoside and quercetin in combination (QH; 1:1) inhibited the growth of human leukemia cells. The aim of the present study was to investigate the anti‑cancer effect of QH on prostate cancer cells. The results demonstrated that QH decreased the production of reactive oxygen species (ROS) and increased antioxidant capacity in PC3 cells at various concentrations (2.5‑60 µg/ml) with peak inhibition and augmentation changes of 3.22‑ and 3.00‑fold, respectively. Following treatment with QH for 48 and 72 h, the IC50-values on PC3 cells were 19.7 and 12.4 µg/ml, respectively. Western blot analysis revealed that QH induced apoptosis in human prostate cancer cells via activation of caspase‑3 and cleavage of poly(adenosine diphosphate ribose) polymerase. In addition, QH significantly inhibited the invasion and migration of PC3 cells as well as reduced the expression of numerous prostate tumor‑associated microRNAs (miRs), including miR‑21, compared to that of untreated human prostate cancer cells. QH was also found to enhance the expression of tumor suppressor programmed cell death protein 4, which was negatively regulated by miR‑21. Furthermore, induced overexpression of miR‑21 using pre‑miR‑21 oligonucleotides attenuated the beneficial effect of QH on prostate cancer cells. In conclusion, the results of the present study indicated that QH exerted an anti‑cancer effect on human prostate cancer cells, the mechanism of which proceeded, at least in part, via the inhibition of the miR‑21 signaling pathway.

View Figures

View References

1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
2	Mottet N, Bellmunt J, Bolla M, et al: EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer. Actas Urol Esp. 35:565–579. 2011.(In Spanish). View Article : Google Scholar : PubMed/NCBI
3	Chuu CP, Kokontis JM, Hiipakka RA, et al: Androgens as therapy for androgen receptor-positive castration-resistant prostate cancer. J Biomed Sci. 18:632011. View Article : Google Scholar : PubMed/NCBI
4	Harzstark AL and Small EJ: Castrate-resistant prostate cancer: therapeutic strategies. Expert Opin Pharmacother. 11:937–945. 2010. View Article : Google Scholar : PubMed/NCBI
5	Theodoratou E, Kyle J, Cetnarskyj R, et al: Dietary flavonoids and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 16:684–693. 2007. View Article : Google Scholar : PubMed/NCBI
6	Choi JA, Kim JY, Lee JY, et al: Induction of cell cycle arrest and apoptosis in human breast cancer cells by quercetin. Int J Oncol. 19:837–844. 2001.PubMed/NCBI
7	Kim MJ, Kim YJ, Park HJ, Chung JH, Leem KH and Kim HK: Apoptotic effect of red wine polyphenols on human colon cancer SNU-C4 cells. Food Chem Toxicol. 44:898–902. 2006. View Article : Google Scholar
8	Tang SN, Singh C, Nall D, Meeker D, Shankar S and Srivastava RK: The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelial-mesenchymal transition. J Mol Signal. 5:142010. View Article : Google Scholar : PubMed/NCBI
9	Srivastava RK, Tang SN, Zhu W, Meeker D and Shankar S: Sulforaphane synergizes with quercetin to inhibit self-renewal capacity of pancreatic cancer stem cells. Front Biosci (Elite Ed). 3:515–528. 2011. View Article : Google Scholar
10	Zou Y, Lu Y and Wei D: Antioxidant activity of a flavonoid-rich extract of Hypericum perforatum L. in vitro. J Agric Food Chem. 52:5032–5039. 2004. View Article : Google Scholar : PubMed/NCBI
11	Gao LL, Feng L, Yao ST, et al: Molecular mechanisms of celery seed extract induced apoptosis via s phase cell cycle arrest in the BGC-823 human stomach cancer cell line. Asian Pac J Cancer Prev. 12:2601–2606. 2011.
12	Mertens-Talcott SU, Talcott ST and Percival SS: Low concentrations of quercetin and ellagic acid synergistically influence proliferation, cytotoxicity and apoptosis in MOLT-4 human leukemia cells. J Nutr. 133:2669–2674. 2003.PubMed/NCBI
13	George J, Singh M, Srivastava AK, et al: Resveratrol and black tea polyphenol combination synergistically suppress mouse skin tumors growth by inhibition of activated MAPKs and p53. PLoS One. 6:e233952011. View Article : Google Scholar : PubMed/NCBI
14	Farazi TA, Spitzer JI, Morozov P and Tuschl T: miRNAs in human cancer. J Pathol. 223:102–115. 2011. View Article : Google Scholar :
15	Si ML, Zhu S, Wu H, Lu Z, Wu F and Mo YY: miR-21-mediated tumor growth. Oncogene. 26:2799–2803. 2007. View Article : Google Scholar
16	Zhu S, Wu H, Wu F, Nie D, Sheng S and Mo YY: MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res. 18:350–359. 2008. View Article : Google Scholar : PubMed/NCBI
17	Chen Y, Liu W, Chao T, et al: MicroRNA-21 down-regulates the expression of tumor suppressor PDCD4 in human glioblastoma cell T98G. Cancer Lett. 272:197–205. 2008. View Article : Google Scholar : PubMed/NCBI
18	Frémont L: Biological effects of resveratrol. Life Sci. 66:663–673. 2000. View Article : Google Scholar : PubMed/NCBI
19	Brauns SC, Dealtry G, Milne P, Naudé R and Van de Venter M: Caspase-3 activation and induction of PARP cleavage by cyclic dipeptide cyclo(Phe-Pro) in HT-29 cells. Anticancer Res. 25:4197–4202. 2005.PubMed/NCBI
20	Selcuklu SD, Donoghue MT and Spillane C: miR-21 as a key regulator of oncogenic processes. Biochem Soc Trans. 37(Pt 4): 918–925. 2009. View Article : Google Scholar : PubMed/NCBI
21	Carew JS and Huang P: Mitochondrial defects in cancer. Mol Cancer. 9:92002. View Article : Google Scholar
22	Fresco P, Borges F, Diniz C and Marques MP: New insights on the anticancer properties of dietary polyphenols. Med Res Rev. 26:747–766. 2006. View Article : Google Scholar : PubMed/NCBI
23	Schumacker PT: Reactive oxygen species in cancer cells: live by the sword, die by the sword. Cancer Cell. 10:175–176. 2006. View Article : Google Scholar : PubMed/NCBI
24	Ling YH, Liebes L, Zou Y and Perez-Soler R: Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic response to Bortezomib, a novel proteasome inhibitor, in human H460 non-small cell lung cancer cells. J Biol Chem. 278:33714–33723. 2003. View Article : Google Scholar : PubMed/NCBI
25	Biasutto L, Szabo’ I and Zoratti M: Mitochondrial effects of plant-made compounds. Antioxid Redox Signal. 15:3039–3059. 2011. View Article : Google Scholar : PubMed/NCBI
26	Hsu SC, Lu JH, Kuo CL, et al: Crude extracts of Solanum lyratum induced cytotoxicity and apoptosis in a human colon adenocarcinoma cell line (colo 205). Anticancer Res. 28(2A): 1045–1054. 2008.PubMed/NCBI
27	Schlachterman A, Valle F, Wall KM, et al: Combined resveratrol, quercetin, and catechin treatment reduces breast tumor growth in a nude mouse model. Transl Oncol. 1:19–27. 2008. View Article : Google Scholar : PubMed/NCBI
28	Tan J, Wang B and Zhu L: Regulation of survivin and Bcl-2 in HepG2 cell apoptosis induced by quercetin. Chem Biodivers. 6:1101–1110. 2009. View Article : Google Scholar : PubMed/NCBI
29	Shakibaei M, John T, Seifarth C and Mobasheri A: Resveratrol inhibits IL-1 beta-induced stimulation of caspase-3 and cleavage of PARP in human articular chondrocytes in vitro. Ann NY Acad Sci. 1095:554–563. 2007. View Article : Google Scholar : PubMed/NCBI
30	Wang ZQ, Stingl L, Morrison C, et al: PARP is important for genomic stability but dispensable in apoptosis. Genes Dev. 11:2347–2358. 1997. View Article : Google Scholar : PubMed/NCBI
31	Hsu CP, Lin YH, Chou CC, et al: Mechanisms of grape seed procyanidin-induced apoptosis in colorectal carcinoma cells. Anticancer Res. 29:283–289. 2009.PubMed/NCBI
32	Li T, Li D, Sha J, Sun P and Huang Y: MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells. Biochem Biophys Res Commun. 383:280–285. 2009. View Article : Google Scholar : PubMed/NCBI
33	Ribas J, Ni X, Haffner M, et al: miR-21: an androgen receptor-regulated microRNA that promotes hormone-dependent and hormone-independent prostate cancer growth. Cancer Res. 69:7165–7169. 2009. View Article : Google Scholar : PubMed/NCBI
34	Pang Y, Young CY and Yuan H: MicroRNAs and prostate cancer. Acta Biochim Biophys Sin (Shanghai). 42:363–369. 2010. View Article : Google Scholar
35	Arbuzova A, Schmitz AA and Vergères G: Cross-talk unfolded: MARCKS proteins. Biochem J. 362(Pt 1): 1–12. 2002. View Article : Google Scholar : PubMed/NCBI
36	Yang HS, Jansen AP, Komar AA, et al: The transformation suppressor Pdcd4 is a novel eukaryotic translation initiation factor 4A binding protein that inhibits translation. Mol Cell Biol. 23:26–37. 2003. View Article : Google Scholar :
37	Bitomsky N, Böhm M and Klempnauer KH: Transformation suppressor protein Pdcd4 interferes with JNK-mediated phosphorylation of c-Jun and recruitment of the coactivator p300 by c-Jun. Oncogene. 23:7484–7493. 2004. View Article : Google Scholar : PubMed/NCBI