Mini-reviewAnthocyanins and their role in cancer prevention
Introduction
Anthocyanins occur ubiquitously in the plant kingdom and confer the bright red, blue and purple colors to fruits and vegetables such as berries, grapes, apples, purple cabbage and corn. Of potential importance to human health is the relatively high concentration of anthocyanins in the diet. The daily intake of anthocyanins in the U.S. diet is estimated to be between 180 and 215 mg whereas, the intake of other dietary flavonoids such as genistein, quercetin and apigenin is only 20–25 mg/day [1]. Epidemiologic studies suggest that the consumption of anthocyanins lowers the risk of cardiovascular disease, diabetes, arthritis and cancer due, at least in part, to their anti-oxidant and anti-inflammatory activities [2].
In the present review, we highlight recent studies on the cancer preventative activities of the anthocyanins, including results from in vitro cell culture and in vivo animal model tumor systems, as well as data from human epidemiological studies. Although laboratory studies have provided some clues on the molecular mechanism(s) by which anthocyanins inhibit carcinogenesis, there is still much to be learned. In addition, the relevance of the in vitro studies to the in vivo situation needs to be confirmed in view of the high concentrations of anthocyanins employed in the in vitro studies.
Section snippets
Chemistry of anthocyanins
Anthocyanins occur naturally in fruits and vegetables as glycosides, having glucose, galactose, rhamnose, xylose or arabinose attached to an aglycon nucleus [3], [4]. In contrast to other flavonoids, the anthocyanins carry a positive charge in acidic solution [3]. They are water-soluble and, depending upon pH and the presence of chelating metal ions, are intensely colored in blue, purple, or red. The de-glycosylated or aglycone forms of anthocyanins are known as anthocyanidins (Fig. 1). The six
Antioxidant effects
The phenolic structure of anthocyanins is responsible for their antioxidant activity; i.e., ability to scavenge reactive oxygen species (ROS) such as superoxide , singlet oxygen (‘O2), peroxide (ROO−), hydrogen peroxide (H2O2), and hydroxyl radical (OH) [5]. The antioxidant effects of anthocyanins in vitro have been demonstrated using several cell culture systems including colon [6], [7], endothelial [8], liver [9], [10], breast [11], [12] and leukemic cells [13], and keratinocytes [14].
Pharmacokinetics and metabolism of anthocyanins
The bioavailability, pharmacokinetics of distribution, and metabolism of anthocyanins in animals and in humans have been summarized in a recent review [60]. In general, in both animals and humans, the anthocyanins are absorbed as intact glycosides, and their absorption and elimination is rapid. However, the efficiency of their absorption is relatively poor [60], [61]. We investigated the absorption and metabolism of black raspberry anthocyanins in humans when administered orally at high doses
Conclusions
Anthocyanins have been shown to exhibit anti-carcinogenic activity against multiple cancer cell types in vitro and tumor types in vivo. Potential cancer chemopreventive activities of anthocyanins revealed from in vitro studies include radical scavenging activity, stimulation of phase II detoxifying enzymes, reduced cell proliferation, inflammation, angiogenesis and invasiveness, and induction of apoptosis and differentiation. The anthocyanins modulate the expression and activation of multiple
References (63)
- et al.
Cyanidin-3-rutinoside, a natural polyphenol antioxidant, selectively kills leukemic cells by induction of oxidative stress
J. Biol. Chem.
(2007) - et al.
Delphinidin, an anthocyanidin in pigmented fruits and vegetables, protects human HaCaT keratinocytes and mouse skin against UVB-mediated oxidative stress and apoptosis
J. Invest. Dermatol.
(2007) - et al.
Analysis and biological activities of anthocyanins
Phytochemistry
(2003) - et al.
Effects of anthocyanidin on the inhibition of proliferation and induction of apoptosis in human gastric adenocarcinoma cells
Food Chem. Toxicol.
(2005) - et al.
Human tumor cell growth inhibition by nontoxic anthocyanidins, the pigments in fruits and vegetables
Life Sci.
(2005) - et al.
Cyanidins: metabolism and biological properties
J. Nutr. Biochem.
(2004) - et al.
Hibiscus anthocyanins rich extract-induced apoptotic cell death in human promyelocytic leukemia cells
Toxicol. Appl. Pharmacol.
(2005) - et al.
Peonidin inhibits phorbol-ester-induced COX-2 expression and transformation in JB6 P+ cells by blocking phosphorylation of ERK-1 and -2
Ann. N. Y. Acad. Sci.
(2007) - et al.
The 1.8-A crystal structure of a matrix metalloproteinase 8-barbiturate inhibitor complex reveals a previously unobserved mechanism for collagenase substrate recognition
J. Biol. Chem.
(2001) - et al.
Black rice anthocyanins inhibit cancer cell invasion via repression of MMPs and u-PA expression
Chem. Biol. Interact.
(2006)
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.
Cancer prevention with freeze-dried berries and berry components
Semin. Cancer Biol.
Chemoprevention of esophageal squamous cell carcinoma
Toxicol. Appl. Pharmacol.
Tart cherry anthocyanins inhibit tumor development in Apc(Min) mice and reduce proliferation of human colon cancer cells
Cancer Lett.
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.
Cyanidin-3-glucoside, a natural product derived from blackberry, exhibits chemopreventive and chemotherapeutic activity
J. Biol. Chem.
Anthocyans from fruits and vegetables – does bright colour signal cancer chemopreventive activity?
Eur. J. Cancer
Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands
Nutr. Cancer
Anthocyanins: structural characteristics that result in unique metabolic patterns and biological activities
Free Radic. Res.
Anthocyanins in grapes and grape products
Crit. Rev. Food Sci. Nutr.
The anthocyanins
Scavenging capacity of berry crops on superoxide radicals, hydrogen peroxide, hydroxyl radicals, and singlet oxygen
J. Agric. Food Chem.
Response of cell cycle/stress-related protein expression and DNA damage upon treatment of CaCo2 cells with anthocyanins
Br. J. Nutr.
Chemical compositions, antioxidant capacities, and antiproliferative activities of selected fruit seed flours
J. Agric. Food Chem.
Anti-angiogenic, antioxidant, and anti-carcinogenic properties of a novel anthocyanin-rich berry extract formula
Biochemistry (Mosc.)
Anthocyanins induce the activation of phase II enzymes through the antioxidant response element pathway against oxidative stress induced apoptosis
J. Agric. Food Chem.
Antioxidant and antiproliferative activities of strawberries
J. Agric. Food Chem.
Anthocyanin-rich grape extract blocks breast cell DNA damage
J. Med. Food
Inhibition of cancer cell proliferation in vitro by fruit and berry extracts and correlations with antioxidant levels
J. Agric. Food Chem.
Suppression of the tumorigenic phenotype in human oral squamous cell carcinoma cells by an ethanol extract derived from freeze-dried black raspberries
Nutr. Cancer
Blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts inhibit growth and stimulate apoptosis of human cancer cells in vitro
J. Agric. Food Chem.
Cited by (820)
Pharmaceutical characterization and exploration of Arkeshwara rasa in MDA-MB-231 cells
2024, Journal of Ayurveda and Integrative MedicineDcbHLH1 interacts with DcMYB1 and DcMYB2 to dynamically regulate petal pigmentation in Dianthus caryophyllus
2024, Industrial Crops and ProductsThe cubosome-based nanoplatforms in cancer therapy: Seeking new paradigms for cancer theranostics
2023, Environmental ResearchRecent advances in tea seeds (Camellia Sinensis (L.) O. Kuntze): Active ingredients, health effects, and potential applications
2023, Trends in Food Science and TechnologyPackaging effects on highly nutritional value beverage obtained by a mix of typical sicilian fruits in accelerated storage
2023, Food Packaging and Shelf Life