Journal Home > Volume 3 , Issue 3-4
Food Science and Human Wellness 2014, 3(3-4): 104-109 https://doi.org/10.1016/j.fshw.2014.11.001
Research Article | Open Access | Issue | Published: 12 November 2014

Efficacious anti-cancer property of flavonoids from citrus peels

Show Author's Information Nancy E. Rawsona,  Chi-Tang Hob,  Shiming Lic( )
AFB International, 3 Research Park Drive, St. Charles, MO 63304, United States
Department of Food Science, Rutgers University, New Brunswick, NJ 08901, United States
Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization, Huanggang Normal University, Huanggang, China

Peer review under responsibility of Beijing Academy of Food Sciences.

Keywords:
Cancer, Efficacy, Flavonoids, Citrus peels, Polymethoxyflavones
Cite this article:
Rawson NE, Ho C-T, Li S. Efficacious anti-cancer property of flavonoids from citrus peels. Food Science and Human Wellness, 2014, 3(3-4): 104-109. https://doi.org/10.1016/j.fshw.2014.11.001
Download citation
EndNote(RIS)
BibTeX

259

Views

31

Downloads

Citations

54

Crossref

N/A

WoS

0

Scopus

0

CSCD

Abstract Full text About this article

Cancer is one of the two leading human fatal diseases. Drug development for cancer intervention has progressed well in past decades yet existing drugs face many limitations in applications and effectiveness and are often associated with serious of side effects, which can further deteriorate the patients’ quality of life. Recent development of natural product based and therapeutically sound anti-cancer agents have gained popularity in the field of functional foods, in which a few have demonstrated efficacy and minimal toxicity toward the prevention and treatment of carcinogenesis. With multiple active molecular components, citrus peels and derived extracts have demonstrated potent efficacious properties against various cancers due in large part to the rich content of flavonoids present in citrus peels. This review summarizes the results of currently available data regarding the in vivo anti-cancer activity of citrus peel flavonoids, and identifies opportunities for subsequent human clinical trials to assess preventive and therapeutic effects in the near future.


menu
Abstract
Full text
Outline
About this article

Efficacious anti-cancer property of flavonoids from citrus peels

Show Author's information Nancy E. Rawsona, Chi-Tang Hob, Shiming Lic( )
AFB International, 3 Research Park Drive, St. Charles, MO 63304, United States
Department of Food Science, Rutgers University, New Brunswick, NJ 08901, United States
Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization, Huanggang Normal University, Huanggang, China

Peer review under responsibility of Beijing Academy of Food Sciences.

Abstract

Cancer is one of the two leading human fatal diseases. Drug development for cancer intervention has progressed well in past decades yet existing drugs face many limitations in applications and effectiveness and are often associated with serious of side effects, which can further deteriorate the patients’ quality of life. Recent development of natural product based and therapeutically sound anti-cancer agents have gained popularity in the field of functional foods, in which a few have demonstrated efficacy and minimal toxicity toward the prevention and treatment of carcinogenesis. With multiple active molecular components, citrus peels and derived extracts have demonstrated potent efficacious properties against various cancers due in large part to the rich content of flavonoids present in citrus peels. This review summarizes the results of currently available data regarding the in vivo anti-cancer activity of citrus peel flavonoids, and identifies opportunities for subsequent human clinical trials to assess preventive and therapeutic effects in the near future.

Keywords: Cancer, Efficacy, Flavonoids, Citrus peels, Polymethoxyflavones

References(52)

[1]

S. Li, M.H. Pan, C.Y. Lo, et al., Chemistry and health effects of polymethoxyflavones and hydroxylated polymethoxyflavones, J. Funct. Foods 1 (2009) 2-12.
DOI Google Scholar
[2]

J.A. Manthey, K. Grohmann, N. Guthrie, Biological properties of citrus flavonoids pertaining to cancer and inflammation, Curr. Med. Chem. 8 (2) (2001) 135-153.
DOI Google Scholar
[3]

J. Londoño-Londoño, V.R. de Lima, O. Lara, et al., Clean recovery of antioxidant flavonoids from citrus peel: optimizing an aqueous ultrasound-assisted extraction method, Food Chem. 119 (2010) 81-87.
DOI Google Scholar
[4]

A. Gosslau, K.Y. Chen, C.T. Ho, et al., Anti-inflammatory effects of characterized orange peel extracts enriched with bioactive polymethoxyflavones, Food Sci. Hum. Wellness 3 (1) (2014) 26-35.
DOI Google Scholar
[5]

S. Li, H. Wang, L. Guo, et al., Chemistry and bioactivity of nobiletin and its metabolites, J. Funct. Foods 6 (2014) 2-10.
DOI Google Scholar
[6]

A. Gosslau, S. Li, K.Y. Chen, et al., The importance of natural product characterization in studies on their anti-inflammatory activity, Mol. Nutr. Food Res. 55 (2011) 74-82.
DOI Google Scholar
[7]

S. Li, Y.C. Lin, C.T. Ho, et al., Formulated extract from multiple citrus peels impairs dendritic cell functions and attenuates allergic contact hypersensitivity, Int. Immunopharmacol. 20 (2014) 12-23.
DOI Google Scholar
[8]

M.C. Kou, S.H. Fu, C.Y. Weng, et al., Effects of citrus flavonoids 5-hydroxy-3,5,6,7,8,3′,4′-hexamethoxyflavone and 3,5,6,7,8,3′,4′-heptamethoxyflavone, on the activities of macrophage scavenger receptors and the hepatic LDL receptor, Food Funct. 4 (2013) 602-609.
DOI Google Scholar
[9]

E.M. Kurowska, J.A. Manthey, Hypolipidemic effects and absorption of citrus polymethoxylated flavones in hamsters with diet-induced hypercholesterolemia, J. Agric. Food Chem. 52 (10) (2004) 2879-2886.
DOI Google Scholar
[10]

S. Gorinstein, A. Caspi, I. Libman, et al., Red grapefruit positively influences serum triglyceride level in patients suffering from coronary atherosclerosis: studies in vitro and in humans, J. Agric. Food Chem. 54 (5) (2006) 1887-1892.
DOI Google Scholar
[11]

J.M. Assini, E.E. Mulvihill, M.W. Huff, Citrus flavonoids and lipid metabolism, Curr. Opin. Lipidol. 24 (1) (2013) 34-40.
DOI Google Scholar
[12]

A. Chanet, D. Milenkovic, C. Manach, et al., Citrus flavones: what is their role in cardiovascular protection? J. Agric. Food Chem. 60 (2012) 8809-8822.
DOI Google Scholar
[13]

N. Parkar, V. Addepalli, Nobiletin ameliorates streptozotocin induced diabetic retinopathy in experimental rats, Discov. Phytomed. 1 (2014) 3-7.
DOI Google Scholar
[14]

A. Nakajima, Y. Aoyama, T.T. Nguyen, et al., Nobiletin, a citrus flavonoid, ameliorates cognitive impairment, oxidative burden, and hyperphosphorylation of tau in senescence-accelerated mouse, Behav. Brain Res. 250 (2013) 351-360.
DOI Google Scholar
[15]

Y. Yabuki, Y. Ohizumi, A. Yokosuka, et al., Nobiletin treatment improves motor and cognitive deficits seen in MPTP-induced Parkinson model mice, Neuroscience 259 (2014) 126-141.
DOI Google Scholar
[16]

S. Li, C.Y. Lo, C.T. Ho, Hydroxylated polymethoxyflavones and methylated flavonoids in sweet orange (Citrus sinensis) peel, J. Agric. Food Chem. 54 (2006) 4176-4185.
DOI Google Scholar
[17]

M.H. Pan, S. Li, C.S. Lai, et al., Inhibition of citrus flavonoids on 12-O-tetradecanoylphorbol 13-acetate-induced skin inflammation and tumorigenesis in mice, Food Sci. Hum. Wellness 1 (2012) 65-73.
DOI Google Scholar
[18]

S. Li, M.H. Pan, C.S. Lai, et al., Isolation and syntheses of polymethoxyflavones and hydroxylated polymethoxyflavones as inhibitors of HL-60 cell lines, Bioorg. Med. Chem. 15 (2007) 3381-3389.
DOI Google Scholar
[19]

C.C. Martinez, V.O. Vicente, Y. Gascon, et al., Treatment of metastatic melanoma B16F10 by the flavonoids tangeretin, rutin, and diosmin, J. Agric. Food Chem. 53 (2005) 6791-6797.
DOI Google Scholar
[20]

K.L. Morley, P.J. Ferguson, J. Koropatnick, Tangeretin and nobiletin induce G1 cell cycle arrest but not apoptosis in human breast and colon cancer cells, Cancer Lett. 251 (2007) 168-178.
DOI Google Scholar
[21]

S.S. Van, V.S. Parmar, S.K. Sharma, et al., Tangeretin inhibits extracellular-signal-regulated kinase (ERK) phosphorylation, FEBS Lett. 579 (2005) 1665-1669.
DOI Google Scholar
[22]

K.H. Chen, M.S. Weng, J.K. Lin, Tangeretin suppresses IL-1 beta-induced cyclooxygenase (COX-2) expression through inhibition of p38 MAPK, JNK, and AKT activation in human lung carcinoma cells, Biochem. Pharmacol. 73 (2007) 215-227.
DOI Google Scholar
[23]

S. Kawaii, Y. Tomono, E. Katase, et al., Antiproliferative activity of flavonoids on several cancer cell lines, Biosci. Biotechnol. Biochem. 63 (1999) 896-899.
DOI Google Scholar
[24]

R. Suzuki, H. Kohno, A. Murakami, et al., Citrus nobiletin inhibits azoxymethane-induced large bowel carcinogenesis in rats, Biofactors 22 (2004) 111-114.
DOI Google Scholar
[25]

K. Kunimasa, M. Ikekita, M. Sato, et al., Nobiletin, a citrus polymethoxyflavonoid, suppresses multiple angiogenesis-related endothelial cell functions and angiogenesis in vivo, Cancer Sci. 101 (11) (2010) 2462-2469.
DOI Google Scholar
[26]

M. Tang, K. Ogawa, M. Asamoto, et al., Protective effects of citrus nobiletin and auraptene in transgenic rats developing adenocarcinoma of the prostate (TRAP) and human prostate carcinoma cells, Cancer Sci. 98 (2007) 471-477.
DOI Google Scholar
[27]

O. Benavente-Garcia, J. Castillo, M. Alcaraz, et al., Beneficial action of citrus flavonoids on multiple cancer-related biological pathways, Curr. Cancer Drug Targets 7 (2007) 795-809.
DOI Google Scholar
[28]

R.R.J. Arroo, K.M. Beresford, A.S. Bhambra, et al., Phytoestrogens as natural prodrugs in cancer prevention: towards a mechanistic model, Phytochem. Rev. (2014), http://dx.doi.org/10.1007/s11101-014-9355-3.
DOI Google Scholar
[29]

A. Murakami, Y. Nakamura, K. Torikai, et al., Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice, Cancer Res. 60 (2000) 5059-5066.
Google Scholar
[30]

N.B. Janakiram, C.V. Rao, Molecular markers and targets for colorectal cancer prevention, Acta Pharmacol. Sin. 29 (2008) 1-20.
DOI Google Scholar
[31]

T. Takayama, S. Katsuki, Y. Takahashi, et al., Aberrant crypt foci of the colon as precursors of adenoma and cancer, N. Engl. J. Med. 339 (1998) 1277-1284.
DOI Google Scholar
[32]

S. Miyamoto, Y. Yasui, T. Tanaka, et al., Suppressive effects of nobiletin on hyperleptinemia and colitis related colon carcinogenesis in male ICR mice, Carcinogenesis 29 (2008) 1057-1063.
DOI Google Scholar
[33]

S. Miyamoto, Y. Yasui, H. Ohigashi, et al., Dietary flavonoids suppress azoxymethane-induced colonic preneoplastic lesions in male C57BL/KsJ-db/db mice, Chem. Biol. Interact. 183 (2010) 276-283.
DOI Google Scholar
[34]

C.S. Lai, S. Li, C.B. Liu, et al., Effective suppression of azoxymethane-induced aberrant crypt foci formation in mice with citrus peel flavonoids, Mol. Nutr. Food Res. 57 (2013) 551-555.
DOI Google Scholar
[35]

M. Takahashi, K. Wakabayashi, Gene mutations and altered gene expression in azoxymethane-induced colon carcinogenesis in rodents, Cancer Sci. 95 (6) (2004) 475-480.
DOI Google Scholar
[36]

M.X. Tang, K. Ogawa, M. Asamoto, et al., Effects of nobiletin on PhIP-induced prostate and colon carcinogenesis in F344 rats, Nutr. Cancer 63 (2011) 227-233.
DOI Google Scholar
[37]

J.A. Hanley, Mortality reductions produced by sustained prostate cancer screening have been underestimated, J. Med. Screen. 17 (3) (2010) 147-151.
DOI Google Scholar
[38]

M.M. Shen, C. Shen, Molecular genetics of prostate cancer: new prospects for old challenges, Genes Dev. 24 (18) (2010) 1967-2000.
DOI Google Scholar
[39]

Z. Obertova, C. Brown, M. Holmes, et al., Prostate cancer incidence and mortality in rural men – a systematic review of the literature, Rural Remote Health 12 (2) (2012) 2039.
DOI Google Scholar
[40]

C. Priolo, M. Agostini, N. Vena, et al., Establishment and genomic characterization of mouse xenografts of human primary prostate tumors, Am. J. Pathol. 176 (4) (2010) 1901-1913.
DOI Google Scholar
[41]

C.S. Lai, S. Li, Y. Miyauchi, et al., Potent anti-cancer effects of citrus peel flavonoids in human prostate xenograft tumors, Food Funct. 4 (6) (2013) 944-949.
DOI Google Scholar
[42]
American Cancer Society. http://www.cancer.org/research/cancerfactsstatistics (accessed 13.10.14).
[43]

G. Luo, X. Guan, L. Zhou, Apoptotic effect of citrus fruit extract nobiletin on lung cancer cell line A549 in vitro and in vivo, Cancer Biol. Ther. 7 (2008) 966-973.
DOI Google Scholar
[44]

H. Ohnishi, M. Asamoto, K. Tujimura, et al., Inhibition of cell proliferation by nobiletin, a dietary phytochemical, associated with apoptosis and characteristic gene expression, but lack of effect on early rat hepatocarcinogenesis in vivo, Cancer Sci. 95 (2004) 936-942.
DOI Google Scholar
[45]

X. Ma, S. Jin, Y. Zhang, et al., Inhibitory effects of nobiletin on heptacellular carcinoma in vitro and in vivo, Phytother. Res. 28 (2014) 560-567.
DOI Google Scholar
[46]

E. Tripoli, M.L. Guardia, S. Giammanco, et al., Citrus flavonoids: molecular structure, biological activity and nutritional properties: a review, Food Chem. 104 (2007) 466-479.
DOI Google Scholar
[47]

G. Gattuso, D. Barreca, C. Gargiulli, et al., Flavonoid composition of citrus juices, Molecules 12 (2007) 1641-1673.
DOI Google Scholar
[48]

M. Lopez-Lazaro, Flavonoids as anti-cancer agents: structure activity relationship study, Curr. Med. Chem. Anticancer Agents 2 (2002) 691-714.
DOI Google Scholar
[49]

L. Wang, J. Wang, L. Fang, et al., Minireview on the anticancer activities of citrus peel polymethoxyflavones related to angiogenesis and others, BioMed Res. Int. 453972 (2014) 1-10.
DOI Google Scholar
[50]

N. Ma, C.S. Lai, C.H. Chung, et al., 5-Demethyltangeretin is more potent than tangeretin in inhibiting dimethylbenz(a)anthrene (DMBA)/12-O-tetradecanoylphorbol-13-acetate(TPA)- induced skin tumorigenesis, J. Funct. Foods 6 (2014) , http://dx.doi.org/10.1016/j.jff.2014.08.009.
DOI Google Scholar
[51]

C.S. Lai, S. Li, C.Y. Chai, et al., Inhibitory effect of citurs 5-hydroxy-3 6,7,8,3′,4′-hexamethoxyflavone on 12-O-tetradecanoylphorbol 13-acetate-induced skin inflammation and tumor promotion in mice, Carcinogenesis 28 (2007) 2582-2588.
DOI Google Scholar
[52]

C.S. Lai, M.L. Tsai, A.C. Cheng, et al., Chemoprevention of colonic tumorigenesis by dietary hydroxylated polymethoxyflavones in azoxymethane-treated mice, Mol. Nutr. Food Res. 55 (2011) 278-290.
DOI Google Scholar
Publication history
Copyright
Rights and permissions

Publication history

Received: 15 October 2014
Accepted: 05 November 2014
Published: 12 November 2014
Issue date: December 2014

Copyright

© 2014 Beijing Academy of Food Sciences.

Rights and permissions

Return