The association was Citrsu strengthened when Citrus bioflavonoids and prostate health for age at diagnosis, Gleason scoreand Bioflavonoide tumor, Citrus bioflavonoids and prostate health, metastasis Citurs, with an HR of bioflavonoifs. Lycopene Non-GMO pet food a phytochemical that belongs to a group of pigments known as carotenoids. Submitted: December 5, Accepted: January 8, Concerningly, men who received high-dose selenium and had the highest baseline plasma selenium levels, had a higher PSA velocity than did men in the placebo group. Human prostate cancer cells were treated with isoflavones, curcumin, or a combination of the two.

Citrus bioflavonoids and prostate health -

Something went wrong. Try again? Cited by. Download options Please wait Article type Paper. Submitted 24 Jan Accepted 18 Apr First published 18 Apr Download Citation. Food Funct. Request permissions. Potent anti-cancer effects of citrus peel flavonoids in human prostate xenograft tumors C.

Social activity. Search articles by author Ching-Shu Lai. Shiming Li. Yutaka Miyauchi. Michiko Suzawa. Chi-Tang Ho. Biomed Chromatogr. Kunimasa K, Ikekita M, Sato M, Ohta T, Yamori Y, Ikeda M, Kuranuki S, Oikawa T: Nobiletin, a citrus polymethoxy flavonoid, suppresses multiple angiogenesis-related endothelial cell functions and angiogenesis in vivo.

Cancer Sci. Nichenametla S, Taruscio TG, Barney DL, Exon JH: A review of the effects and mechanisms of polyphenolics in cancer. Crit Rev Food Sci Nutr. Murakami A, Nakamura Y, Torikai K, Tanaka T, Koshiba T, Koshimizu K, Kuwahara S, Takahashi Y, Ogawa K, Yano M, Tokuda H, Nishino H, Mimaki Y, Sashida Y, Kitanaka S, Ohigashi H: Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice.

Cancer Res. Kim SJ, Uehara H, Yazici S, Langley RR, He J, Tsan R, Fan D, Killion JJ, Fidler IJ: Simultaneous blockade of platelet-derived growth factor-receptor and epidermal growth factor-receptor signaling and systemic administration of paclitaxel as therapy for human prostate cancer metastasis in bone of nude mice.

Kim SJ, Johnson M, Koterba K, Herynk MH, Uehara H, Gallick GE: Reduced c-Met expression by an adenovirus expressing a c-Met ribozyme inhibits tumorigenic growth and lymph node metastases of PC3-LN4 prostate tumor cells in an orthotopic nude mouse model.

Clin Cancer Res. Pulukuri SM, Gondi CS, Lakka SS, Jutla A, Estes N, Gujrati M, Rao JS: RNA interference-directed knockdown of urokinase plasminogen activator and urokinase plasminogen activator receptor inhibits prostate cancer cell invasion, survival, and tumorigenicity in vivo.

Journal of Biological Chemisry. Article CAS Google Scholar. Tang M, Ogawa K, Asamoto M, Hokaiwado N, Seeni A, Suzuki S, Takahashi S, Tanaka T, Ichikawa K, Shirai T: Protective effects of citrus nobiletin and auraptene in transgenic rats developing adenocarcinoma of the prostate TRAP and human prostate carcinoma cells.

Fang J, Zhou Q, Shi XL, Jiang BH: Luteolin inhibits insulin-like growth factor 1receptor signaling in prostate cancer cells. Aggarwal BB: Nuclear-factor-κB: The enemy within.

Cancer Cell. Gilmore TD: Introduction to NF-κB: players, pathways, perspectives. Bharti AC, Aggarwal BB: Nuclear factor-κB and cancer: Its role in prevention and therapy. Biochem Pharmacol. Kim MO, Moon DO, Heo MS, Lee JD, Jung JH, Kim SK, Choi YH, Kim GY: Pectenotoxin-2 abolishes constitutively activated NF-κB, leading to suppression of NF-κB related gene products and potentiation of apoptosis.

Cancer Letter. Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB: NF-κB activation by tumour necrosis factor requires the Akt serine-threonine kinase. Uden PV, Kenneth NS, Rocha S: Regulation of hypoxia-inducible factor-1α by NF-κB.

Biochemical Journal. Article PubMed PubMed Central Google Scholar. Journal of Pathology. Chu EC, Tarnawski AS: PTEN regulatory functions in tumor suppression and cell biology. Med Sci Monit. Download references.

This research was supported by a West Virginia Experimental Program to Stimulate Competitive Research grant and an NIH grant 5P20RR and 8P20GM from the National Center for Research Resources awarded to the West Virginia IDeA Network of Biomedical Research Excellence. College of Biosystems Engineering and Food Science, Fuli Institute of Food Science, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou, , China.

College of Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV, , USA. Department of Pharmaceutical Science, West Virginia University, Morgantown, WV, , USA. Department of Pharmacology, Physiology and Toxicology, Joan C.

Edwards School of Medicine, Marshall University, Huntington, WV, , USA. You can also search for this author in PubMed Google Scholar. Correspondence to Yi Charlie Chen. JC carried out the majority of experimental work.

YC drafted the manuscript. All authors participated in experimental design and read and approved the final manuscript. This article is published under license to BioMed Central Ltd.

Reprints and permissions. Chen, J. et al. Nobiletin suppresses cell viability through AKT Pathways in PC-3 and DU prostate cancer cells.

BMC Pharmacol Toxicol 15 , 59 Download citation. Received : 06 June Accepted : 14 October Published : 24 October Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Abstract Background Nobiletin is a non-toxic dietary flavonoid that possesses anti-cancer properties.

Methods Nobiletin was isolated from a polymethoxy flavonoid mixture using HPLC, cell viability was analyzed with MTS-based assays. Results Data showed that nobiletin decreased cell viability in both prostate cell lines, with a greater reduction in viability in PC-3 cells. Conclusion Taken together, our results show that nobiletin suppresses cell viability through AKT pathways, with a more profound effect against the more metastatic PC-3 line.

Background Prostate cancer is the second most common cancer in the United States, as well as, the second leading cause of mortality among males in the western world [ 1 ]. Western blot Prostate cancer cells 10 6 were seeded in mm dishes and incubated for 16 h before treatment with nobiletin for 24 h.

Results Isolation and identification of nobiletin Nobiletin was prepared from a polymethoxy flavonoid mixture, which was provided by Zhejiang Quzhou Tiansheng Plant Extraction Co.

Figure 1. Full size image. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Figure 7. Figure 8. Figure 9. Conclusion Our research indicated that nobiletin is a good candidate for the chemoprevention of prostate cancer in humans and could be an effective measure in suppressing prostate cancer cell viability.

References Mohile SG, Shelke AR: Treating prostate cancer in elderly men: how does aging affect the outcome?. Article PubMed Google Scholar Crawford E: Understanding the epidemiology, natural history, and key pathways involved in prostate cancer. Article Google Scholar Bosland MC: The role of steroid hormones in prostate carcinogenesis.

Article CAS PubMed Google Scholar Crawford E: Epidemiology of prostate cancer. Article PubMed Google Scholar Gronberg H: Prostate cancer epidemiology. Article PubMed Google Scholar Whittemore AS, Kolonel LN, Wu AH, John EM, Gallagher RP, Howe GR: Prostate cancer in relation to diet, physical activity, and body size in blacks, whites, and Asians in the United States and Canada.

Article CAS PubMed Google Scholar Gupta S, Kim J, Prasad S, Aggarwal B: Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals.

Article CAS PubMed PubMed Central Google Scholar Meiyanto E, Hermawan A, Anindyajati : Natural products for cancer-targeted therapy: citrus flavonoids as potent chemopreventive agents. Article PubMed Google Scholar Yang C, Wang X, Lu G, Picinich S: Cancer prevention by tea: animal studies, molecular mechanisms and human relevance.

Article CAS PubMed PubMed Central Google Scholar Gates M, Vitonis A, Tworoger S, Rosner B, Titus-Ernstoff L, Hankinson S, Cramer H: Flavonoid intake and ovarian cancer risk in a population based case-control study. Article CAS PubMed PubMed Central Google Scholar McCann S, Freudenheim J, Marshall J, Saxon G: Risk of human ovarian cancer is related to dietary intake of selected nutrients, phytochemicals and food groups.

CAS PubMed Google Scholar Bernini R, Crisante F, Ginnasi MC: A convenient and safe O-methylation offlavonoids with dimethyl carbonate DMC. Article CAS PubMed Google Scholar Knekt P, Järvinen R, Seppänen R, Heliövaara M, Teppo L, Pukkala E, Aromaa A: Dietary flavonoids and the risk of lung cancer and other malignant neoplasms.

Article CAS PubMed Google Scholar Li S, Yu H, Ho CT: Nobiletin: efficient and large quantity isolation from orange peel extract. Article CAS PubMed Google Scholar Kunimasa K, Ikekita M, Sato M, Ohta T, Yamori Y, Ikeda M, Kuranuki S, Oikawa T: Nobiletin, a citrus polymethoxy flavonoid, suppresses multiple angiogenesis-related endothelial cell functions and angiogenesis in vivo.

Article CAS PubMed Google Scholar Nichenametla S, Taruscio TG, Barney DL, Exon JH: A review of the effects and mechanisms of polyphenolics in cancer. Article CAS PubMed Google Scholar Murakami A, Nakamura Y, Torikai K, Tanaka T, Koshiba T, Koshimizu K, Kuwahara S, Takahashi Y, Ogawa K, Yano M, Tokuda H, Nishino H, Mimaki Y, Sashida Y, Kitanaka S, Ohigashi H: Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice.

CAS PubMed Google Scholar Kim SJ, Uehara H, Yazici S, Langley RR, He J, Tsan R, Fan D, Killion JJ, Fidler IJ: Simultaneous blockade of platelet-derived growth factor-receptor and epidermal growth factor-receptor signaling and systemic administration of paclitaxel as therapy for human prostate cancer metastasis in bone of nude mice.

Article CAS PubMed Google Scholar Kim SJ, Johnson M, Koterba K, Herynk MH, Uehara H, Gallick GE: Reduced c-Met expression by an adenovirus expressing a c-Met ribozyme inhibits tumorigenic growth and lymph node metastases of PC3-LN4 prostate tumor cells in an orthotopic nude mouse model. Alam MA, Subhan N, Rahman MM, et al.

Effect of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanisms of action. Adv Nutr ; Fuhrman B, Aviram M. Flavonoids protect LDL from oxidation and attenuate atherosclerosis. Curr Opin Lipidol ; Naderi GA, Asgary S, Sarraf-Zadegan GN, Shirvany H.

Antioxidant effect of flavonoids on the susceptibility of LDL oxidation. Mol Cell Biochem ; Mahmoud AM, Hernández Bautista RJ, Mansur A, et al. Beneficial effects of citrus flavonoids on cardiovascular and metabolic health.

Oxid Med Cell Longev ; Kurowska EM, Borradaile NM, Spence JD, Carroll KK. Hypocholesterolemic effects of dietary citrus juices in rabbits. Nutr Res ; Kim HK, Jeong TS, Lee MK, et al.

Lipid lowering efficacy of hesperetin metabolites in high-cholesterol fed rats. Clin Chim Acta ; Chtourou Y, Fetoui H, Jemai R, et al.

Naringenin reduces cholesterol induced hepatic inflammation in rats by modulating matrix metalloproteinases-2, 9 via inhibition of nuclear factor κB pathway.

Eur J Pharmacol ; Kurowska EM, Manthey JA. Hypolipidemic effects and absorption of citrus polymethoxylated flavones in hamsters with diet induced hypercholesterolemia. Park HJ, Jung UJ, Cho SJ, et al. Lee S, Park YB, Bae KH, et al. Cholesterol lowering activity of naringenin via inhibition of 3- hydroxymethylglutaryl coenzyme A reductase and acyl coenzyme A: cholesterol acyltransferase in rats.

Ann Nutr Metab ; Lee MK, Moon SS, Lee SE, et al. Naringenin 7-O-cetyl ether as inhibitor of HMG-CoA reductase and modulator of plasma and hepatic lipids in high cholesterol-fed rats. Bioorg Med Chem ; Chanet A, Milenkovic D, Deval C, et al. Naringin, the major grapefruit flavonoid, specifically affects atherosclerosis development in diet-induced hypercholesterolemia in mice.

Lee CH, Jeong TS, Choi YK, et al. Anti-atherogenic effect of citrus flavonoids, naringin and naringenin, associated with hepatic ACAT and aortic VCAM-1 and MCP-1 in high cholesterol-fed rabbits.

Biophys Res Commun ; Lee S, Lee CH, Moon SS, et al. Naringenin derivatives as anti-atherogenic agents. Bioorg Med Chem Lett ; Mulvihill EE, Assini JM, Sutherland BG, et al.

Naringenin decreases progression of atherosclerosis by improving dyslipidemia in high fat-fed low density lipoprotein receptor-null mice. Arterioscler Thromb Vasc Biol ; Oboh G, Bello FO, Ademosun AO.

Hypocholesterolemic properties of grapefruit Citrus paradisii and shaddock Citrus maxima juices and inhibition of angiotensinconverting enzyme activity. J Food Drug Anal ; Angelone T, Pasqua T, Di Majo D, et al. Distinct signalling mechanisms are involved in the dissimilar myocardial and coronary effects elicited by quercetin and myricetin, two red wine flavonols.

Nutr Metab Cardiovasc Dis ; Mink PJ, Scrafford CG, Barraj LM, et al. Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. Am J Clin Nutr ;85; Aptekmann NP, Cesar TB. Long-term orange juice consumption is associated with low LDL-cholesterol and apolipoprotein B in normal and moderately hypercholesterolemic subjects.

Lipids Health Dis ; Yamada T, Hayasaka S, Shibata Y, et al. Frequency of citrus fruit intake is associated with the incidence of cardiovascular disease: the Jichi Medical School cohort study.

J Epidemiol ; Gorinstein S, Caspi A, Libman I, et al. Red grapefruit positively influences serum triglyceride level in patients suffering from coronary atherosclerosis: studies in vitro and in humans.

J Agr Food Chem ; Miwa Y, Yamada M, Sunayama T, et al. Effects of glucosyl hesperidin on serum lipids in hyperlipidemic subjects: preferential reduction in elevated serum triglyceride level. J Nutr Sci Vitaminol ; Miwa Y, Mitsuzumi H, Sunayama T, et al.

Glucosyl hesperidin lowers serum triglyceride level in hypertriglyceridemic subjects through the improvement of very low density lipoprotein metabolic abnormality. Jung UJ, Kim HJ, Lee JS, et al. Naringin supplementation lowers plasma lipids and enhances erythrocyte antioxidant enzyme activities in hypercholesterolemic subjects.

Clin Nutr ; Roza JM, Xian-Liu Z, Guthrie N. Effect of citrus flavonoids and tocotrienols on serum cholesterol levels in hypercholesterolemic subjects. Altern Ther Health Med ; Reshef N, Hayari Y, Goren C, et al.

Antihypertensive effect of sweetie fruit in patients with stage I hypertension. Am J Hypertens ; Morand C, Dubray C, Milenkovic D, et al. Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers.

Rizza S, Muniyappa R, Iantorno M, et al. Citrus polyphenol hesperidin stimulates production of nitric oxide in endothelial cells while improving endothelial function and reducing in-flammatory markers in patients with metabolic syndrome.

J Clin Endocrinol Metab ; Benavente-Garcìa O, Castillo J, Marin FR, et al. Uses and properties of citrus flavonoids. Manach C, Regerat F, Texier O, et al. Bioavailability, metabolism and physiological impact of 4-oxo-flavonoids.

Van Wauwe J, Goossens J. Effects of antioxidants on cyclooxygenase and lipoxygenase activities in intact human platelets: Comparison with indomethacin and ETYA.

Prostaglandins ; Tzeng SH, Ko WC, Ko FN, Teng CM. Inhibition of platelet aggregation by some flavonoids. Thromb Res ; Alcaraz MJ, Ferrandiz ML. Modification of arachidonic metabolism by flavonoids. J Ethnopharmacol ; Reyes-Farias M, Carrasco-Pozo C.

The anticancer effect of quercetin: Molecular implications in cancer metabolism. Int J Mol Sci ; Aghajanpour M, Nazer MR, Obeidavi Z, et al. Functional foods and their role in cancer prevention and health promotion: a comprehensive review. Am J Cancer Res ; Rawson NE, Ho CT, Li S.

Efficacious anticancer property of flavonoids from citrus peels. Food Sci Human Wellness ; Shimoi K, Masuda S, Furogori M, et al. Radioprotective affect of antioxidative flavonoids in c-ray irradiated mice. Carcinogenesis ; Jeon SM, Bok SH, Jang MK, et al. Antioxidative activity of naringin and lovastatin in high cholesterol-fed rabbits.

Life Sci ; Heo HY, Lee SJ, Kwon CH, et al. Anticlastogenic effects of galangin against bleomycin-induced chromosomal aberrations in mouse spleen lymphocytes. Mut Res ; So FV, Guthrie N, Chambers AF, et al. Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices.

Nutr Cancer ; Wesołowska O, Wisniewski J, Roda-Pomianek KS, et al. Multidrug resistance reversal and apoptosis induction in human colon cancer cells by some flavonoids present in citrus plants. J Nat Prod ; Scambia G, Ranelletti FO, Benedetti-Panici P, et al.

Quercetin potentiates the effect of adriamycin in a multidrug resistant MCF-7 human breast cancer cell line: P-glycoprotein as a possible target. Cancer Chemother Pharmacol ; Manthey JA, Guthrie N. Antiproliferative activities of citrus flavonoids against six human cancer cell lines.

Larocca LM, Piantelli M, Leone G, et al. Type II oestrogen binding sites in acute lymphoid and myeloid leukaemias: Growth inhibitory effect of oestrogen and flavonoids.

Br J Haematol ; Yoshida M, Sakai T, Hosokawa N, et al. The effect of quercetin on cell cycle progression and growth of human gastric cancer cells. FEBS Lett ; Inhibitory effect of quercetin on OVCA cells and presence of type II oestrogen binding sites in primary ovariun tumors and cultured cells.

Br J Cancer ; Feletto E, Yu XQ, Lew JB, et al. Trends in colon and rectal cancer incidence in Australia from to Analysis of data on over , cases. Cancer Epidemiol Biomarkers Prev ; Miyamoto S, Yasui Y, Tanaka T, et al.

Complementary Hydration and weight loss Citrus bioflavonoids and prostate health prostqte CAM is a form of treatment used in addition to complementary or instead of alternative standard treatments. In prosate Citrus bioflavonoids and prostate health States, about biorlavonoids out of Citrs 8 men bioflqvonoids be bioflavonoidw with prostate cancer. It is the most second-most common cancer in men in the United States. CAM use among men with prostate cancer is common. Studies of why men with prostate cancer decide to use CAM show that their choice is based on medical historybeliefs about the safety and side effects of CAM compared to standard treatments, and a need to feel in control of their treatment. CAM treatments used by men with prostate cancer include certain foods, dietary supplementsherbsvitaminsand minerals. Bioflwvonoids fruits are Creatine and diabetes main fruits of the Mediterranean prostaet and Citrus bioflavonoids and prostate health been prostaet recognized for their beneficial Citrus bioflavonoids and prostate health on human health. Cittus studies have shown a significant association between dietary flavonoid intake and reduced risk of cardiovascular and malignant diseases. The beneficial effects of citrus Citrus bioflavonoids and prostate health on human health appear to be due to their high content in vitamins, minerals and fibers. In particular, the antioxidant and anti-inflammatory activities have been indicated as some of the mechanisms through which citrus fruits may thwart the development of chronic degenerative diseases such as atherosclerosis and cancer. This review would critically examine the results from numerous experimental and clinical studies carried out in order assess the contribute of citrus flavonoids to the prevention of chronic pathological conditions including atherosclerosis and cancer. Adefegha SA. Functional foods and nutraceuticals as dietary intervention in chronic diseases; novel perspectives for health promotion and disease prevention.