Effects of anthocyanins on the prevention and treatment of cancer

British Journal of Pharmacology

Volumn 174, Issue 11, 2017, Pages 1226-1243

  Lin, Bo Wen ^a   Gong, Cheng Chen ^a   Song, Hai Fei ^a   Cui, Ying Yu ^a,b  

^a TONGJI UNIVERSITY SCHOOL OF MEDICINE   (China)

^b BEIJING UNIVERSITY OF POSTS AND TELECOMMUNICATIONS   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ANTHOCYANIN; CASPASE 12; CASPASE 7; CYANIDIN; MALVIDIN CHLORIDE; MITOGEN ACTIVATED PROTEIN KINASE P38; PELARGONIDIN; PEONIDIN; PETUNIDIN; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROTEIN BCL 2; PROTEIN P21; PROTEIN P27; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR; ANTINEOPLASTIC AGENT; ANTIOXIDANT;

ANTIANGIOGENIC ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTIINVASION ACTIVITY; ANTIMUTAGENESIS ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; AUTOPHAGY; CANCER CELL; CANCER CHEMOTHERAPY; CANCER GROWTH; CANCER MODEL; CANCER PREVENTION; CANCER STAGING; CELL ADHESION; CELL CYCLE ARREST; CELL TRANSFORMATION; DOWN REGULATION; DRUG ACTIVITY; DRUG EFFECT; DRUG MECHANISM; DRUG SENSITIVITY; DRUG STRUCTURE; ENDOPLASMIC RETICULUM; GENE EXPRESSION REGULATION; HUMAN; INTRACELLULAR SIGNALING; LYSOSOME; MEDICAL RESEARCH; METASTASIS INHIBITION; MULTIDRUG RESISTANCE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; REVIEW; SIGNAL TRANSDUCTION; UPREGULATION; ANIMAL; DRUG EFFECTS; DRUG RESISTANCE; NEOPLASM;

ANIMALS; ANTHOCYANINS; ANTICARCINOGENIC AGENTS; ANTINEOPLASTIC AGENTS; ANTIOXIDANTS; DRUG RESISTANCE, NEOPLASM; HUMANS; NEOPLASMS; SIGNAL TRANSDUCTION;

EID: 84996879678     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.13627     Document Type: Review

References (138)

1. Afaq F, Saleem M, Krueger CG, Reed JD, Mukhtar H (2005). Anthocyanin- and hydrolyzable tannin-rich pomegranate fruit extract modulates MAPK and NF-kappaB pathways and inhibits skin tumorigenesis in CD-1 mice. Int J Cancer 113: 423–433.
2. Alexander SPH, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E et al. (2015a). The Concise Guide to PHARMACOLOGY 2015/16: Overview. Br J Pharmacol 172: 5729–5143.
3. Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE et al. (2015b). The Concise Guide to PHARMACOLOGY 2015/16: Catalytic receptors. Br J Pharmacol 172: 5979–6023.
4. Alexander SPH, Cidlowski JA, Kelly E, Marrion N, Peters JA, Benson HE et al. (2015c). The Concise Guide to PHARMACOLOGY 2015/16: Nuclear hormone receptors. Br J Pharmacol 172: 5956–5978.
5. Alexander SPH, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E et al. (2015d). The Concise Guide to PHARMACOLOGY 2015/16: Transporters. Br J Pharmacol 172: 6110–6202.
6. Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE et al. (2015e). The Concise Guide to PHARMACOLOGY 2015/16: Enzymes. Br J Pharmacol 172: 6024–6109.
7. Alvarez-Suarez JM, Giampieri F, Tulipani S, Casoli T, Stefano GD, González-Paramás AM et al. (2014). One-month strawberry-rich anthocyanin supplementation ameliorates cardiovascular risk, oxidative stress markers and platelet activation in humans. J Nutr Biochem 25: 289–294.
8. Andres-Lacueva C, Shukitt-Hale B, Galli RL, Jauregui O, Lamuela-Raventos RM, Joseph JA (2005). Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutr Neurosci 8: 111–120.
9. Anwar S, Fratantonio D, Ferrari D, Saija A, Cimino F, Speciale A (2016). Berry anthocyanins reduce proliferation of human colorectal carcinoma cells by inducing caspase-3 activation and p21 upregulation. Mol Med Rep 14: 1397–1403.
10. Aqil F, Gupta A, Munagala R, Jeyabalan J, Kausar H, Sharma RJ et al. (2012). Antioxidant and antiproliferative activities of anthocyanin/ellagitannin-enriched extracts from Syzygium cumini L. Jamun, the Indian Blackberry. Nutr Cancer 64: 428–438.
11. Bagchi D, Sen CK, Bagchi M, Atalay M (2004). Anti-angiogenic, antioxidant, and anti-carcinogenic properties of a novel anthocyanin-rich berry extract formula. Biochemistry (Mosc) 69: 75–80.
12. Bishayee A, Haskell Y, Do C, Siveen KS, Mohandas N, Sethi G et al. (2016). Potential benefits of edible berries in the management of aerodigestive and gastrointestinal tract cancers: preclinical and clinical evidence. Crit Rev Food Sci Nutr 56: 1753–1775.
13. Bishayee A, Mbimba T, Thoppil RJ, Haznagy-Radnai E, Sipos P, Darvesh AS et al. (2011). Anthocyanin-rich black currant (Ribes nigrum L.) extract affords chemoprevention against diethylnitrosamine-induced hepatocellular carcinogenesis in rats. J Nutr Biochem 22: 1035–1046.
14. Bobe G, Wang B, Seeram NP, Nair MG, Bourquin LD (2006). Dietary anthocyanin-rich tart cherry extract inhibits intestinal tumorigenesis in APC(Min) mice fed suboptimal levels of sulindac. J Agric Food Chem 54: 9322–9328.
15. Bornsek SM, Ziberna L, Polak T, Vanzo A, Ulrih NP, Abram V et al. (2012). Bilberry and blueberry anthocyanins act as powerful intracellular antioxidants in mammalian cells. Food Chem 134: 1878–1884.
16. Bowen-Forbes CS, Zhang Y, Nair MG (2010). Anthocyanin content, antioxidant, anti-inflammatory and anticancer properties of blackberry and raspberry fruits. J Food Compos Anal 23: 554–560.
17. Bunea A, Rugina D, Sconta Z, Pop RM, Pintea A, Socaciu C et al. (2013). Anthocyanin determination in blueberry extracts from various cultivars and their antiproliferative and apoptotic properties in B16-F10 metastatic murine melanoma cells. Phytochemistry 95: 436–444.
18. Burton LJ, Smith BA, Smith BN, Loyd Q, Nagappan P, McKeithen D et al. (2015). Muscadine grape skin extract can antagonize Snail-cathepsin L-mediated invasion, migration and osteoclastogenesis in prostate and breast cancer cells. Carcinogenesis 36: 1019–1027.
19. Carbonaro M, Nardini M, Maselli P, Nucara A (2015). Chemico-physical and nutritional properties of traditional legumes (lentil, Lens culinaris L., and grass pea, Lathyrus sativus L.) from organic agriculture: an explorative study. Org Agri 5: 1–9.
20. Cerletti C, de Curtis A, Bracone F, Digesu C, Morganti AG, Iacoviello L et al. (2016). Dietary anthocyanins and health: data from FLORA and ATHENA EU projects. Br J Clin Pharmacol. doi:10.1111/bcp.12943.
21. Četojević-Simin DD, Velićanski AS, Cvetković DD, Markov SL, Ćetković GS, Šaponjac VTT et al. (2015). Bioactivity of Meeker and Willamette raspberry (Rubus idaeus L.) pomace extracts. Food Chem 166: 407–413.
22. Chang H, Yu B, Yu X, Yi L, Chen C, Mi M et al. (2010). Anticancer activities of an anthocyanin-rich extract from black rice against breast cancer cells in vitro and in vivo. Nutr Cancer 62: 1128–1136.
23. Chang YC, Huang HP, Hsu JD, Yang SF, Wang CJ (2005). Hibiscus anthocyanins rich extract-induced apoptotic cell death in human promyelocytic leukemia cells. Toxicol Appl Pharmacol 205: 201–212.
24. Charepalli V, Reddivari L, Radhakrishnan S, Vadde R, Agarwal R, Vanamala JK (2015). Anthocyanin-containing purple-fleshed potatoes suppress colon tumorigenesis via elimination of colon cancer stem cells. J Nutr Biochem 26: 1641–1649.
25. Charepalli V, Reddivari L, Vadde R, Walia S, Radhakrishnan S, Vanamala JK (2016). Eugenia jambolana (Java Plum) fruit extract exhibits anti-cancer activity against early stage human HCT-116 colon cancer cells and colon cancer stem cells. Cancers (Basel) 8: 29.
26. Chen CY, Yi L, Jin X, Zhang T, Fu YJ, Zhu JD et al. (2011). Inhibitory effect of delphinidin on monocyte-endothelial cell adhesion induced by oxidized low-density lipoprotein via ROS/p38MAPK/NF-kappaB pathway. Cell Biochem Biophys 61: 337–348.
27. Chen MH, McClung AM, Bergman CJ (2016a). Bran data of total flavonoid and total phenolic contents, oxygen radical absorbance capacity, and profiles of proanthocyanidins and whole grain physical traits of 32 red and purple rice varieties. Data Brief 8: 6–13.
28. Chen PN, Chu SC, Chiou HL, Chiang CL, Yang SF, Hsieh YS (2005). Cyanidin 3-glucoside and peonidin 3-glucoside inhibit tumor cell growth and induce apoptosis in vitro and suppress tumor growth in vivo. Nutr Cancer 53: 232–243.
29. Chen WC, Liu HM, Liu JS (2016b). Progress in the research on anti-carcinogenic activities of anthocyanins (Chinese). Food Res Dev 37: 211–215.
30. Chen XY, Zhou J, Luo LP, Han B, Li F, Chen JY et al. (2015). Black rice anthocyanins suppress metastasis of breast cancer cells by targeting RAS/RAF/MAPK pathway. Biomed Res Int 2015: 1–11.
31. Cocate PG, Natali AJ, Oliveira A, Longo GZ, Alfenas Rde C, Peluzio Mdo C et al. (2014). Fruit and vegetable intake and related nutrients are associated with oxidative stress markers in middle-aged men. Nutrition 30: 660–665.
32. Cooke D, Steward WP, Gescher AJ, Marczylo T (2005). Anthocyans from fruits and vegetables--does bright colour signal cancer chemopreventive activity? Eur J Cancer 41: 1931–1940.
33. Cooper-Driver GA (2001). Contributions of Jeffrey Harborne and co-workers to the study of anthocyanins. Phytochemistry 56: 229–236.
34. Correa-Betanzo J, Allen-Vercoe E, Mcdonald J, Schroeter K, Corredig M, Paliyath G (2014). Stability and biological activity of wild blueberry (Vaccinium angustifolium) polyphenols during simulated in vitro gastrointestinal digestion. Food Chem 165: 522–531.
35. Cui J, Li XY (2014). Progress on anti-tumor mechanisms of anthocyanins Chinese. Food Sci 35: 310–315.
36. Cui YY, Xie H, Wang JF (2005b). Potential biomedical properties of Pinus massoniana bark extract. Phytother Res 19: 34–38.
37. Cui YY, Xie H, Qi KB, He YM, Wang JF (2005a). Effects of Pinus massoniana bark extract on cell proliferation and apoptosis of human hepatoma BEL-7402 cells. World J Gastroenterol 11: 5277–5282.
38. Dai J, Gupte A, Gates L, Mumper RJ (2009). A comprehensive study of anthocyanin-containing extracts from selected blackberry cultivars: extraction methods, stability, anticancer properties and mechanisms. Food Chem Toxicol 47: 837–847.
39. De Ferrars RM, Czank C, Zhang Q, Botting NP, Kroon PA, Cassidy A et al. (2014). The pharmacokinetics of anthocyanins and their metabolites in humans. Br J Pharmacol 171: 3268–3282.
40. Dreiseitel A, Oosterhuis B, Vukman KV, Schreier P, Oehme A, Locher S et al. (2009). Berry anthocyanins and anthocyanidins exhibit distinct affinities for the efflux transporters BCRP and MDR1. Br J Pharmacol 158: 1942–1950.
41. Esposito D, Chen A, Grace MH, Komarnytsky S, Lila MA (2014). Inhibitory effects of wild blueberry anthocyanins and other flavonoids on biomarkers of acute and chronic inflammation in vitro. J Agric Food Chem 62: 7022–7028.
42. Esselen M, Boettler U, Teller N, Bachler S, Hutter M, Rufer CE et al. (2011). Anthocyanin-rich blackberry extract suppresses the DNA-damaging properties of topoisomerase I and II poisons in colon carcinoma cells. J Agric Food Chem 59: 6966–6973.
43. Feng R, Wang SY, Shi YH, Fan J, Yin XM (2010). Delphinidin induces necrosis in hepatocellular carcinoma cells in the presence of 3-methyladenine, an autophagy inhibitor. J Agric Food Chem 58: 3957–3964.
44. Fernandes I, Faria A, Calhau C, Freitas VD, Mateus N (2014). Bioavailability of anthocyanins and derivatives. J Funct Foods 7: 54–66.
45. Filipiak K, Hidalgo M, Silvan JM, Fabre B, Carbajo RJ, Pineda-Lucena A et al. (2014). Dietary Gallic acid and anthocyanin cytotoxicity on human fibrosarcoma HT1080 cells. A study on the mode of action. Food Funct 5: 381–389.
46. Fimognari C, Berti F, Nusse M, Cantelli-Forti G, Hrelia P (2004). Induction of apoptosis in two human leukemia cell lines as well as differentiation in human promyelocytic cells by cyanidin-3-O-beta-glucopyranoside. Biochem Pharmacol 67: 2047–2056.
47. Ha US, Bae WJ, Kim SJ, Yoon BI, Hong SH, Lee JY et al. (2015). Anthocyanin induces apoptosis of DU-145 cells in vitro and inhibits xenograft growth of prostate cancer. Yonsei Med J 56: 16–23.
48. Hafidh RR, Abdulamir AS, Bakar FA, Jalilian FA, Jahanshiri F, Abas F et al. (2013). Novel anticancer activity and anticancer mechanisms of Brassica oleracea L. var. capitata F. rubra. Eur J Intern Med 5: 450–464.
49. Hagiwara A, Miyashita K, Nakanishi T, Sano M, Tamano S, Kadota T et al. (2001). Pronounced inhibition by a natural anthocyanin, purple corn color, of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-associated colorectal carcinogenesis in male F344 rats pretreated with 1,2-dimethylhydrazine. Cancer Lett 171: 17–25.
50. Haseeb A, Chen D, Haqqi TM (2013). Delphinidin inhibits IL-1beta-induced activation of NF-kappaB by modulating the phosphorylation of IRAK-1(Ser376) in human articular chondrocytes. Rheumatology (Oxford) 52: 998–1008.
51. He J, Giusti MM (2010). Anthocyanins: natural colorants with health-promoting properties. Annu Rev Food Sci Technol 1: 163–187.
52. Ho ML, Chen PN, Chu SC, Kuo DY, Kuo WH, Chen JY et al. (2010). Peonidin 3-glucoside inhibits lung cancer metastasis by downregulation of proteinases activities and MAPK pathway. Nutr Cancer 62: 505–516.
53. Holton TA, Cornish EC (1995). Genetics and biochemistry of anthocyanin biosynthesis. Plant Cell 7: 1071–1083.
54. Hou DX, Kai K, Li JJ, Lin S, Terahara N, Wakamatsu M et al. (2004). Anthocyanidins inhibit activator protein 1 activity and cell transformation: structure–activity relationship and molecular mechanisms. Carcinogenesis 25: 29–36.
55. Hou DX, Yanagita T, Uto T, Masuzaki S, Fujii M (2005). Anthocyanidins inhibit cyclooxygenase-2 expression in LPS-evoked macrophages: structure–activity relationship and molecular mechanisms involved. Biochem Pharmacol 70: 417–425.
56. Huang HP, Chang YC, Wu CH, Hung CN, Wang CJ (2012). Anthocyanin-rich Mulberry extract inhibit the gastric cancer cell growth in vitro and xenograft mice by inducing signals of p38/p53 and c-jun. Food Chem 129: 1703–1709.
57. Huang L, Zhang Z, Zhang S, Ren J, Zhang R, Zeng H et al. (2011). Inhibitory action of Celastrol on hypoxia-mediated angiogenesis and metastasis via the HIF-1alpha pathway. Int J Mol Med 27: 407–415.
58. Jeong JW, Lee WS, Shin SC, Kim GY, Choi BT, Choi YH (2013). Anthocyanins downregulate lipopolysaccharide-induced inflammatory responses in BV2 microglial cells by suppressing the NF-kappaB and Akt/MAPKs signaling pathways. Int J Mol Sci 14: 1502–1515.
59. Jian H, Giusti MM (2010). Anthocyanins: natural colorants with health-promoting properties. Annu Rev Food Sci Technol 1: 163–187.
60. Jiang X, Tang X, Zhang P, Liu G, Guo H (2014). Cyanidin-3- O -β-glucoside protects primary mouse hepatocytes against high glucose-induced apoptosis by modulating mitochondrial dysfunction and the PI3K/Akt pathway. Biochem Pharmacol 90: 135–144.
61. Jin HL, Lim JD, Choung MG (2013). Studies on the anthocyanin profile and biological properties from the fruits of Acanthopanax senticosus Siberian ginseng. J Funct Foods 5: 380–388.
62. Jing P, Giusti MM (2010). Contribution of Berry Anthocyanins to Their Chemopreventive Properties. Springer: New York, pp. 3–40.
63. Kang NJ, Lee KW, Kwon JY, Hwang MK, Rogozin EA, Heo YS et al. (2008). Delphinidin attenuates neoplastic transformation in JB6 Cl41 mouse epidermal cells by blocking Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling. Cancer Prev Res (Phila) 1: 522–531.
64. Kausar H, Jeyabalan J, Aqil F, Chabba D, Sidana J, Singh IP et al. (2012). Berry anthocyanidins synergistically suppress growth and invasive potential of human non-small-cell lung cancer cells. Cancer Lett 325: 54–62.
65. Kay CD (2006). Aspects of anthocyanin absorption, metabolism and pharmacokinetics in humans. Nutr Res Rev 19: 137–146.
66. Kitagawa S (2006). Inhibitory effects of polyphenols on p-glycoprotein-mediated transport. Biol Pharm Bull 29: 1–6.
67. Kocic B, Filipovic S, Nikolic M, Petrovic B (2011). Effects of anthocyanins and anthocyanin-rich extracts on the risk for cancers of the gastrointestinal tract. J BUON 16: 602–608.
68. Konczak-Islam I, Yoshimoto M, Hou DX, Terahara N, Yamakawa O (2003). Potential chemopreventive properties of anthocyanin-rich aqueous extracts from in vitro produced tissue of sweetpotato Ipomoea batatas L. J Agric Food Chem 51: 5916–5922.
69. Kresty LA, Frankel WL, Hammond CD, Baird ME, Mele JM, Stoner GD et al. (2006). Transitioning from preclinical to clinical chemopreventive assessments of lyophilized black raspberries: interim results show berries modulate markers of oxidative stress in Barrett's esophagus patients. Nutr Cancer 54: 148–156.
70. Kuntz S, Kunz C, Rudloff S (2015). Inhibition of pancreatic cancer cell migration by plasma anthocyanins isolated from healthy volunteers receiving an anthocyanin-rich berry juice. Eur J Nutr 22: 1–12.
71. Lamy S, Beaulieu E, Labbe D, Bedard V, Moghrabi A, Barrette S et al. (2008). Delphinidin, a dietary anthocyanidin, inhibits platelet-derived growth factor ligand/receptor (PDGF/PDGFR) signaling. Carcinogenesis 29: 1033–1041.
72. Lamy S, Lafleur R, Bedard V, Moghrabi A, Barrette S, Gingras D et al. (2007). Anthocyanidins inhibit migration of glioblastoma cells: structure–activity relationship and involvement of the plasminolytic system. J Cell Biochem 100: 100–111.
73. Lee SH, Park SM, Park SM, Park JH, Shin DY, Kim GY et al. (2009). Induction of apoptosis in human leukemia U937 cells by anthocyanins through down-regulation of Bcl-2 and activation of caspases. Int J Oncol 34: 1077–1083.
74. Lee YK, Lee WS, Kim GS, Park OJ (2010). Anthocyanins are novel AMPKalpha1 stimulators that suppress tumor growth by inhibiting mTOR phosphorylation. Oncol Rep 24: 1471–1477.
75. Li D, Zhang Y, Liu Y, Sun R, Xia M (2015a). Purified anthocyanin supplementation reduces dyslipidemia, enhances antioxidant capacity, and prevents insulin resistance in diabetic patients. J Nutr 145: 742–748.
76. Li K, Li Q, Li J, Zhang T, Han Z, Gao D et al. (2007). Antitumor activity of the procyanidins from Pinus koraiensis bark on mice bearing U14 cervical cancer. Yakugaku Zasshi 127: 1145–1151.
77. Li WX, Bao YH, Wang ZY (2011). Morphological observation of apoptotic human colon cancer cells ht29 induced by anthocyanins from Lonicera edulis (Chinese). Acta Nutrimenta Sinica 33: 575–579.
78. Li X, Xu J, Tang X, Liu Y, Yu X, Wang Z et al. (2016a). Anthocyanins inhibit trastuzumab-resistant breast cancer in vitro and in vivo. Mol Med Rep 13: 4007–4013.
79. Li YW, Wang D, Li XG, Jin Y (2014). Anthocyanins extracted from Chinese blueberry and its anticancer effects on HepG2 cells. Adv Mat Res : 887–888.
80. Li YY, Feng J, Zhang XL, Cui YY (2015b). Pine bark extracts: nutraceutical, pharmacological, and toxicological evaluation. J Pharmacol Exp Ther 353: 9–16.
81. Li YY, Feng J, Zhang XL, Li MQ, Cui YY (2016b). Effects of Pinus massoniana bark extract on the invasion capability of HeLa cells. J Funct Foods 24: 520–526.
82. Lila MA, Burton-Freeman B, Grace M, Kalt W (2016). Unraveling anthocyanin bioavailability for human health. Annu Rev Food Sci Technol 7: 375–393.
83. Lim S, Xu J, Kim J, Chen TY, Su X, Standard J et al. (2013a). Role of anthocyanin-enriched purple-fleshed sweet potato p40 in colorectal cancer prevention. Mol Nutr Food Res 57: 1908–1917.
84. Lim TG, Jung SK, Kim JE, Kim Y, Lee HJ, Jang TS et al. (2013b). NADPH oxidase is a novel target of delphinidin for the inhibition of UVB-induced MMP-1 expression in human dermal fibroblasts. Exp Dermatol 22: 428–430.
85. Limtrakul P, Yodkeeree S, Pitchakarn P, Punfa W (2015). Suppression of inflammatory responses by black rice extract in RAW 264.7 macrophage cells via downregulation of NF-kB and AP-1 signaling pathways. Asian Pac J Cancer Prev 16: 4277–4283.
86. Liu HL, Jiang WB, Xie MX (2010). Flavonoids: recent advances as anticancer drugs. Recent Pat Anticancer Drug Discov 5: 152–164.
87. Liu J, Zhou J, Wu Z, Wang X, Liu L, Yao C (2016). Cyanidin 3-O-beta-glucoside ameliorates ethanol-induced acute liver injury by attenuating oxidative stress and apoptosis: the role of SIRT1/FOXO1 signaling. Alcohol Clin Exp Res 40: 457–466.
88. Liu-Smith F, Meyskens FL (2016). Molecular mechanisms of flavonoids in melanin synthesis and the potential for the prevention and treatment of melanoma. Mol Nutr Food Res 60: 1264–1274.
89. Longo L, Platini F, Scardino A, Alabiso O, Vasapollo G, Tessitore L (2008). Autophagy inhibition enhances anthocyanin-induced apoptosis in hepatocellular carcinoma. Mol Cancer Ther 7: 2476–2485.
90. Luo LP, Han B, Yu XP, Chen XY, Zhou J, Chen W et al. (2014). Anti-metastasis activity of black rice anthocyanins against breast cancer: analyses using an ErbB2 positive breast cancer cell line and tumoral xenograft model. Asian Pac J Cancer Prev 15: 6219–6225.
91. Malik M, Zhao C, Schoene N, Guisti MM, Moyer MP, Magnuson BA (2003). Anthocyanin-rich extract from Aronia meloncarpa E induces a cell cycle block in colon cancer but not normal colonic cells. Nutr Cancer 46: 186–196.
92. Marko D, Puppel N, Tjaden Z, Jakobs S, Pahlke G (2004). The substitution pattern of anthocyanidins affects different cellular signaling cascades regulating cell proliferation. Mol Nutr Food Res 48: 318–325.
93. Martincorena I, Campbell PJ (2015). Somatic mutation in cancer and normal cells. Science 349: 1483–1489.
94. Mauray A, Felgines C, Morand C, Mazur A, Scalbert A, Milenkovic D (2012). Bilberry anthocyanin-rich extract alters expression of genes related to atherosclerosis development in aorta of apo E-deficient mice. Nutr Metab Cardiovas 22: 72–80.
95. McGhie TK, Walton MC (2007). The bioavailability and absorption of anthocyanins: towards a better understanding. Mol Nutr Food Res 51: 702–713.
96. Miyake S, Takahashi N, Sasaki M, Kobayashi S, Tsubota K, Ozawa Y (2012). Vision preservation during retinal inflammation by anthocyanin-rich bilberry extract: cellular and molecular mechanism. Lab Invest 92 (1): 102–109.
97. Naomi K, Keiko I, Tojiro T, Koji Y, Masuko K (2003). Induction of apoptosis in cancer cells by Bilberry (Vaccinium myrtillus) and the anthocyanins. J Agric Food Chem 51 (1): 68–75.
98. Nimptsch K, Zhang X, Cassidy A, Song M, O'Reilly EJ, Lin JH et al. (2016). Habitual intake of flavonoid subclasses and risk of colorectal cancer in 2 large prospective cohorts. Am J Clin Nutr 103: 184–191.
99. Núñez-Sánchez MA, Gonzalez-Sarrias A, Romo-Vaquero M, Garcia-Villalba R, Selma MV, Tomas-Barberan FA et al. (2015). Dietary phenolics against colorectal cancer--From promising preclinical results to poor translation into clinical trials: Pitfalls and future needs. Mol Nutr Food Res 59: 1274–1291.
100. Oak MH, Bedoui JE, Madeira SV, Chalupsky K, Schini-Kerth VB (2006). Delphinidin and cyanidin inhibit PDGF(AB)-induced VEGF release in vascular smooth muscle cells by preventing activation of p38 MAPK and JNK. Br J Pharmacol 149: 283–290.
101. Pace C, Giacosa S, Torchio F, Segade SR, Cagnasso E, Rolle L (2014). Extraction kinetics of anthocyanins from skin to pulp during carbonic maceration of winegrape berries with different ripeness levels. Food Chem 165: 77–84.
102. Pal HC, Sharma S, Strickland LR, Agarwal J, Athar M, Elmets CA et al. (2013). Delphinidin reduces cell proliferation and induces apoptosis of non-small-cell lung cancer cells by targeting EGFR/VEGFR2 signaling pathways. PLoS One 8: 108–110.
103. Park MY, Kim JM, Kim JS, Choung MG, Sung MK (2015). Chemopreventive Action of anthocyanin-rich black soybean fraction in APC (Min/+) intestinal polyposis model. J Cancer Prev 20: 193–201.
104. Pascual-Teresa SD (2014). Molecular mechanisms involved in the cardiovascular and neuroprotective effects of anthocyanins. Arch Biochem Biophys 559: 68–74.
105. Peiffer DS, Zimmerman NP, Wang LS, Ransom BW, Carmella SG, Kuo CT et al. (2014). Chemoprevention of esophageal cancer with black raspberries, their component anthocyanins, and a major anthocyanin metabolite, protocatechuic acid. Cancer Prev Res (Phila) 7: 574–584.
106. Reddivari L, Vanamala J, Chintharlapalli S, Safe SH, Miller JC Jr (2007). Anthocyanin fraction from potato extracts is cytotoxic to prostate cancer cells through activation of caspase-dependent and caspase-independent pathways. Carcinogenesis 28: 2227–2235.
107. Rugina D, Sconta Z, Leopold L, Pintea A, Bunea A, Socaciu C (2012). Antioxidant activities of chokeberry extracts and the cytotoxic action of their anthocyanin fraction on HeLa human cervical tumor cells. J Med Food 15: 700–706.
108. Sarma AD, Sreelakshmi Y, Sharma R (1997). Antioxidant ability of anthocyanins against ascorbic acid oxidation. Phytochemistry 45: 671–674.
109. Schiavano GF, De Santi M, Brandi G, Fanelli M, Bucchini A, Giamperi L et al. (2015). Inhibition of breast cancer cell proliferation and in vitro tumorigenesis by a new red apple cultivar. PLoS One 10: 1–17.
110. Semaming Y, Pannengpetch P, Chattipakorn SC, Chattipakorn N (2015). Pharmacological properties of protocatechuic acid and its potential roles as complementary medicine. Evid Based Complement Alternativ Med 2015: 1–11.
111. Serafino A, Sinibaldi-Vallebona P, Lazzarino G, Tavazzi B, Rasi G, Pierimarchi P et al. (2004). Differentiation of human melanoma cells induced by cyanidin-3-O-beta-glucopyranoside. FASEB J 18: 1940–1942.
112. Shih PH, Yeh CT, Yen GC (2007). Anthocyanins induce the activation of phase II enzymes through the antioxidant response element pathway against oxidative stress-induced apoptosis. J Agric Food Chem 55: 9427–9435.
113. Shin DY, Lu JN, Kim GY, Jung JM, Kang HS, Lee WS et al. (2011). Anti-invasive activities of anthocyanins through modulation of tight junctions and suppression of matrix metalloproteinase activities in HCT-116 human colon carcinoma cells. Oncol Rep 25: 567–572.
114. Singletary KW, Jung KJ, Giusti M (2007). Anthocyanin-rich grape extract blocks breast cell DNA damage. J Med Food 10: 244–251.
115. Song NR, Yang H, Park J, Kwon JY, Kang NJ, Yong SH et al. (2012). Cyanidin suppresses neoplastic cell transformation by directly targeting phosphatidylinositol 3-kinase. Food Chem 133: 658–664.
116. Southan C, Sharman JL, Benson HE, Faccenda E, Pawson AJ, Alexander SP et al. (2016). NC-IUPHAR. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. Nucleic Acids Res 44 (D1): D1054–D1068.
117. Srivastava A, Akoh CC, Fischer J, Krewer G (2007). Effect of anthocyanin fractions from selected cultivars of Georgia-grown blueberries on apoptosis and phase II enzymes. J Agric Food Chem 55: 3180–3185.
118. Stoner GD, Sardo C, Apseloff G, Mullet D, Wargo W, Pound V et al. (2005). Pharmacokinetics of anthocyanins and ellagic acid in healthy volunteers fed freeze-dried black raspberries daily for 7 days. J Clin Pharmacol 45: 1153–1164.
119. Syed DN, Afaq F, Sarfaraz S, Khan N, Kedlaya R, Setaluri V et al. (2008). Delphinidin inhibits cell proliferation and invasion via modulation of Met receptor phosphorylation. Toxicol Appl Pharmacol 231: 52–60.
120. Teller N, Thiele W, Boettler U, Sleeman J, Marko D (2009a). Delphinidin inhibits a broad spectrum of receptor tyrosine kinases of the ErbB and VEGFR family. Mol Nutr Food Res 53: 1075–1083.
121. Teller N, Thiele W, Marczylo TH, Gescher AJ, Boettler U, Sleeman J et al. (2009b). Suppression of the kinase activity of receptor tyrosine kinases by anthocyanin-rich mixtures extracted from bilberries and grapes. J Agric Food Chem 57: 3094–3101.
122. Thoppil RJ, Bhatia D, Barnes KF, Haznagy-Radnai E, Hohmann J, Darvesh AS et al. (2012). Black currant anthocyanins abrogate oxidative stress through Nrf2- mediated antioxidant mechanisms in a rat model of hepatocellular carcinoma. Curr Cancer Drug Targets 12: 1244–1257.
123. Thwe A, Valan Arasu M, Li X, Park CH, Kim SJ, Al-Dhabi NA et al. (2016). Effect of different agrobacterium rhizogenes strains on hairy root induction and phenylpropanoid biosynthesis in tartary buckwheat (Fagopyrum tataricum Gaertn). Front Microbiol 7: 1–10.
124. Tsai TC, Huang HP, Chang YC, Wang CJ (2014). An anthocyanin-rich extract from Hibiscus sabdariffa linnaeus inhibits N-nitrosomethylurea-induced leukemia in rats. J Agric Food Chem 62: 1572–1580.
125. Tsuyuki S, Fukui S, Watanabe A, Akune S, Tanabe M, Yoshida K (2012). Delphinidin induces autolysosome as well as autophagosome formation and delphinidin-induced autophagy exerts a cell protective role. J Biochem Mol Toxicol 26: 445–453.
126. Wang LS, Stoner GD (2008). Anthocyanins and their role in cancer prevention. Cancer Lett 269: 281–290.
127. Wang LS, Hecht SS, Carmella SG, Yu N, Larue B, Henry C et al. (2009). Anthocyanins in black raspberries prevent esophageal tumors in rats. Cancer Prev Res (Phila) 2: 84–93.
128. Weisel T, Baum M, Eisenbrand G, Dietrich H, Will F, Stockis JP et al. (2006). An anthocyanin/polyphenolic-rich fruit juice reduces oxidative DNA damage and increases glutathione level in healthy probands. Biotechnol J 1: 388–397.
129. Welch CR, Wu Q, Simon JE (2008). Recent advances in anthocyanin analysis and characterization. Curr Anal Chem 4: 75–101.
130. Wu T, Yu Z, Tang Q, Song H, Gao Z, Chen W et al. (2013). Honeysuckle anthocyanin supplementation prevents diet-induced obesity in C57BL/6 mice. Food Funct 4: 1654–1661.
131. Xu M, Bower KA, Wang S, Frank JA, Chen G, Ding M et al. (2010). Cyanidin-3-glucoside inhibits ethanol-induced invasion of breast cancer cells overexpressing ErbB2. Mol Cancer 9: 285.
132. Yang M, Koo SI, Song WO, Chun OK (2011). Food matrix affecting anthocyanin bioavailability: review. Curr Med Chem 18: 291–300.
133. Yi L, Chen CY, Jin X, Mi MT, Yu B, Chang H et al. (2010). Structural requirements of anthocyanins in relation to inhibition of endothelial injury induced by oxidized low-density lipoprotein and correlation with radical scavenging activity. FEBS Lett 584: 583–590.
134. Yoshimoto M, Okuno S, Yoshinaga M, Yamakawa O, Yamaguchi M, Yamada J (1999). Antimutagenicity of sweetpotato (Ipomoea batatas) roots. Biosci Biotechnol Biochem 63: 537–541.
135. Yu J, Xu Y, Khaoustov V, Yoffe B (2011). Identification of components of grape powder with anti-apoptotic effects. Toxicol Ind Health 27: 19–28.
136. Yun JW, Lee WS, Min JK, Jing NL, Kang MH, Kim HG et al. (2010). Characterization of a profile of the anthocyanins isolated from Vitis coignetiae Pulliat and their anti-invasive activity on HT-29 human colon cancer cells. Food Chem Toxicol 48: 903–909.
137. Zhang JH, Feng DR, Ma HL, Liu B, Wang HB, Xie H et al. (2012). Antitumor effects of Pinus massoniana bark extract in murine sarcoma S180 both in vitro and in vivo. Am J Chin Med 40: 861–875.
138. Zhu H, Ma J, Wang Q, Hou M, Tang Z, Guo H (2008). Anthocyanin attenuates CD40-mediated endothelial cell activation and apoptosis by inhibiting CD40-induced MAPK activation. Atherosclerosis 202: 41–47.