Table 3.
Anticarcinogenic effects of berry extracts or constituents in vitro and/or in vivo models of colon cancer.
| Berry Extracts/Fraction/Component | Model (Cell Lines or Animal) | Duration and Dose/Intervention | Effects on Colon Cancer | References |
|---|---|---|---|---|
| Raspberry | ||||
| In vitro | ||||
| Polyphenolic-rich extracts | HT-29 and HCT-115 cells | 0, 3.125, 6.25, 12.5, 25, 50 μg/mL for 24 h | -Inhibit initiation, promotion and invasion. | [131] |
| Anthocyanins rich extracts of black raspberry | HCT-116, Caco-2 and SW480 cells | 0.5, 5, and 25 μg/mL for 3 days | -Inhibit proliferation. -Suppress DNMT1 and DNMT3B proteins. -Suppress downstream of Wnt pathway. -Induce apoptosis. |
[130] |
| ET and their derivatives from black raspberry seeds | HT-29 cells | 5 to 30 μg/mL for 24 and 48 h | -Arrest cell cycle. -Induce apoptosis by extrinsic and intrinsic pathways. |
[132] |
| Aqueous extracts of black raspberry | HT-29 cells | 0 to 400 µg/mL for 24 to 48 h | -Inhibit cancer cell growth -Induce apoptosis. |
[133] |
| Red raspberry extracts | LoVo cells | 5%, 7.5%, and 10% for 24 to 48 h | -Reduce the survival of cells. | [134] |
| Black raspberry extracts | HT-29 and HCT-116 cells | 25–200 µg/mL for 48 h | -Induce cytotoxic effects. | [59] |
| Gastrointestinal digestion and colonic fermentation | HT-29 and HT-115 cells | 0–50 µg/mL gallic acid equivalents (GAE) for 24 h. | -Exert anti-genotoxic, anti-mutagenic and anti-invasive activity. | [116] |
| Freeze-dried extracts from black raspberry | HT-29 cells | 0.6 and 1.2 mg of extract/mL for 48 h | -Retain their anticancer activity after digestion. | [135] |
| In vivo | ||||
| Lyophilized black raspberry | AOM induced Fischer 344 rat | 0%, 2.5%, 5%, or 10% (wt/wt) for 9 to 33 weeks | -Decrease the multiplicity of ACF, total tumors, adenomas, and adenocarcinomas. | [136] |
| Black raspberry extracts | Interleukin-10 knock-out mouse | 5% for 8 weeks | -Decrease colonic ulceration. | [137] |
| Freeze-dried black raspberry | Apc1638+/− mice and Muc2−/− mice | 10% for 12 weeks | -Lower tumor incidence and multiplicity. | [138] |
| DSS induced male C57BL/6J mice | 5%–10% for 7–14 days | -Ameliorates ulcerative colitis. -Suppresses inflammation. |
[139] | |
| DSS induced male C57BL/6J mice | 5% for 28 days | -Suppresses colonic ulceration by correcting promoter hypermethylation of suppressor genes. | [140] | |
| Blueberry | ||||
| In vitro | ||||
| Dried extracts and fractions | HT-29 and Caco-2 cells | 50–10,000 µg/mL for 48 h | -Inhibit cancer cell proliferation. -Induce apoptosis. |
[141] |
| Ethanol/water extracts | HT-29 cells | 0.025%–0.5% dry wt for 24 h | -Exert antiproliferative activity. | [142] |
| Anthocyanin-rich extracts | Caco-2 cells | 0.1–100 nM for 1 h | -Act as an intracellular antioxidant. | [143] |
| DLD-1 and COLO205 cells | 50–250 μg/mL for 24 h | -Repress the proliferation. -Induce apoptosis. |
[144] | |
| Blueberry extracts | HT-29 and HCT116 cells | 25–200 µg/mL for 24 to 48 h | -Inhibit cancer cell proliferation. | [145] |
| IVD and colonic fermentation | HT-29 or CRL-1790 cells | 10, 25, 50, 75 or 100 µg/mL for 24 to 48 h | -Alter antiproliferative and antioxidant activity after digestion. | [146] |
| Delphinidin | HCT116 cells | 30–240 mM for 48 h | -Inhibit cancer cell growth. -Induce apoptosis. -Arrest cell cycle. |
[147] |
| Anthocyanin-enriched fractions | HT-29 cells | 50–150 µg/mL for 6 h | -Induce apoptosis. | [148] |
| Pterostilbene | HT-29 cells | 50 µM for 4 h | -Suppresses cell growth. -Suppresses inflammation. |
[149] |
| In vivo | ||||
| Pterostilbene | AOM induce Fisher 344 male | 40 p.p.m. (0.004%) for 45 weeks | -Reduce tumor multiplicity, by inhibiting the Wnt/β-catenin signaling pathway. | [149] |
| Blueberry extracts | AOM induce Fisher 344 male | 50 g/kg for 13 weeks | -Reduce formation of AOM-induced ACF and increase in hepatic GST activity. | [150] |
| Blueberry husks and mixture of three probiotic | DSS treatment rat | 50 g /kg diet for 6 months | -Reduce colonic ulcers and dysplastic lesions. | [151] |
| Grape | ||||
| In vitro | ||||
| Grape seed proanthocyanidin extract | Caco-2 cells | 10–100 µg/mL for 24 h | -Inhibits cancer cell proliferation. -Reduces PI3k/PKB signaling pathway. -Induces caspase-3 dependent apoptosis. |
[152] |
| Anthocyanin-rich extracts | HT-29 cells | 0 to 200 μg/mL for 48 h | -Inhibit cell proliferation. | [153] |
| HT-29 cells | 10–75 µg of monomeric anthocyanin/mL for 24–72 h | -Induce anti-proliferative activity. | [154] | |
| HT-29 cells | 500 µg/ml for 72 h | -Protect DNA damaging properties of topoisomerase poisons. | [155] | |
| Obacunone and obacunone glucoside (OG) from seeds of marsh white grape | SW480 cells | 6.25, 12.5, 50, and 100 µM for 24, 48 and 72 h | -Induce intrinsic pathway of apoptosis. | [156] |
| Grape waste | Caco-2 cells | 0.5, 1.5, 10, 50, or 100 mL/L for 24 h | -Induce strong antiradical and antiproliferative activity. -Arrest cells cycle. |
[157] |
| In vivo | ||||
| Anthocyanin-rich extracts | AOM treated Fischer 344 male rats | 3.85 g of monomeric anthocyanin/kg body weight for 14 weeks | -Inhibit colonic aberrant crypt foci formation. | [158] |
| Total pholyphenolic extracts | DMH induced F344 rats | 0.11 % (w/w) for 16 weeks | -Decrease number of adenomas. | [159] |
| Proanthocyanidin-rich dietary fiber | C57BL/6J mice | 10 mL/kg body weight for 2 weeks | -Alters the expression of tumor suppressor genes and proto-oncogenes. -Modulates genes associated with lipid biosynthesis, energy metabolism, cell cycle, and apoptosis. |
[160] |
| Strawberry | ||||
| In vitro | ||||
| Crude extracts and purified compounds | HT-29 and HCT-116 cells | 250 μg/mL (crude extract) and 100 μg/mL (pure compounds) for 48 h | -Inhibit cell proliferation. | [161] |
| Polyphenol-rich extracts | Caco-2 cells | 25, 50, and 75 μg of GAE /mL | -Show anti neoplastic activity. | [162] |
| Strawberry extracts | HT-29 cells | 0.025%, 0.05%, 0.25%, 0.5% for 24 h | -Organically grow strawberry extracts show higher antiproliferative activity. | [163] |
| HT-29 and HCT-116 cells | 25–200 µg/mL for 24 to 72 h | -Inhibit cancer cell proliferation. | [145] | |
| IVD and fecal fermentation | HT-29 and HT-115 cells | 0–50 µg/mL GAE for 24 h | -Exerts anti-genotoxic, anti-mutagenic and anti-invasive activity. | [116] |
| Extracts from strawberries treated with essential oils | HT-29 cells | 3 mg/mL for 24 h to 96 h | -Exhibit strong radical scavenging capacity and antiproliferative activity. | [164] |
| Kaempferol | HT-29 cells | 0 or 60 μmol/L for 24 to 72 h | -Inhibit cancer cells growth. -Arrest cell cycle. |
[165] |
| ET extracts, EA and UA. | Human 293T cells | 10–1000 µg/mL for 48 h | -Inhibit the canonical Wnt signaling pathway. | [166] |
| In vivo | ||||
| Freeze-dried strawberry | AOM/DSS induced male Crj: CD-1 mice | 2.5%, 5.0% or 10.0% for 20 weeks | -Reduce proinflammatory mediators and oncogenic signaling pathways. | [167] |
| Bilberry | ||||
| In vitro | ||||
| Ethanol extracts | HCT-116 cells | 4 mg/mL for 24 or 48 h | -Inhibit cancer cell proliferation. | [168] |
| Anthocyanin-rich extracts | HT-29 cell | 25–75 μg/mL (equivalents as cyanidin 3 glucoside) for 48 h | -Inhibit cell proliferation | [153] |
| HT-29 cells | 0–60 mg/mL for 24 h | -Inhibit cancer cell proliferation. -Induce apoptosis. |
[168] | |
| HT-29 cells | 50–500 µg/mL for 72 h | -Suppress the DNA-damaging properties. | [155] | |
| HT-29 cells | 5–500 µg/mL for 1 to 24 h | -Exhibit cytotoxicity. -Decrease DNA damage and ROS level. |
[169] | |
| Anthocyanin-rich extracts | HT-29 and NCM460 cells | 10–75 µg of monomeric anthocyanin/mL for 24–72 h | -Inhibit cancer cell proliferation. | [154] |
| Anthocyanin-rich extracts | Caco-2 cells | 0.1–100 nM for 1 h | -Exert potent intracellular antioxidant activity. | [143] |
| In vivo | ||||
| Anthocyanin-rich extracts | AOM treated Fischer 344 male rats | 3.85 g of monomeric anthocyanin/kg for 14 weeks | -Decrease the number of total and large ACF. | [158] |
| Mirtoselect and cyanidin-3-glucoside | Apc Min/+ mouse | 0.03%–0.3% for 12 weeks | -Decrease the total numbers of intestine adenomas. | [170] |
| Freeze-dried bilberry | Apc Min/+ mouse | 1564 mg/kg for 10 weeks | -Inhibit the formation of intestinal adenoma. | [171] |
| Cranberry | ||||
| In vitro | ||||
| Cranberry presscake and whole cranberry extract | HT-29 cells | 0–600 mg/mL for 4 days | -Exhibit antiproliferative activity. | [172] |
| Cranberry extracts and polyphenol fraction | HCT-116, SW480 and SW620 cells | 50–200 μg/mL (extract) and 6.5–78.8 μg/mL (fractions) for 48 h | -Enhance antiproliferative activity. | [173] |
| In vivo | ||||
| Cranberry extracts and dried cranberry | DSS induced murine colitis | 0.1% creanberry extract and 1.5% dry cranberry for 1 week | -Prevent colitis. -Decrease inflammatory cytokines. |
[174] |
| Cranberry products | AOM induced Fisher 344 male | 50 g/kg for 17 weeks | -Inhibit colonic ACF formation. | [150] |
| Fr6 and purified proanthocyanidin | Xenografts Balb/c mice | 100 mg/kg proanthocyanidin and 250 mg/kg Fr6 for every 2 days for 3 weeks | -Decrease tumor growth and volume. | [175] |
| Juice of high-bush cranberry | DMH treated mouse | 65% gilaburu pulp and 45% water (pH: 3.09) for 30 weeks | -Inhibit tumor lesion at the initiation stage. | [176] |
| Mangosteen | ||||
| In vitro | ||||
| α-Mangostin and other xanthones extracts | HCT-116 cells | 2.5–30 μg/mL for 48 h | -Induce cytotoxicity and apoptosis. | [71] |
| α-Mangostin | HCT-116 cells | 14.8–25.6 µM for 24 h | -Inhibit proliferation. -Induce apoptosis and arrest cell cycle. |
[177] |
| DLD-1 cells | 0 to 20 µM for 24 h | -Inhibit proliferation. -Induce apoptosis. |
[178] | |
| HT-29 cells | 6–12 μM for 24 h | -Exert anti-proliferative activity. -Decrease Bcl-2 and β-catenin expresion. |
[179] | |
| γ-Mangostin | HT-29 cells | 10–200 μM for 24 h | -Inhibits cancer cell proliferation. -Induces apoptosis and increases ROS. |
[180] |
| In vivo | ||||
| Extracts of mangosteen pericarp | Established subcutaneous tumor of HCT-116 cells in NCR nude mice | 0.25% and 0.5% for 20 days | -Inhibit tumor growth and fewer blood vessels in tumor. | [181] |
| α-Mangostin | HT-29 colon cell xenogrft Balb/c nu/nu mice | 900 mg /kg for 2 or 4 weeks | -Decrease tumor masses and anti-apoptotic protein, Bcl-2, and β-catenin. | [179] |
| Her2/CT26 colon cell xenografts mice | 20 mg/kg daily for 3 days | -Reduce tumor growth by autophagy activation. | [182] | |
| DMH induce Fisher 344 rats | 0.02% and 0.05% for 5 weeks | -Inhibit development of ACF. -Decreases dysplastic foci, β-catenin accumulated crypts and lower PCNA. |
[183] | |
| Crude methanolic extract | Mice were implanted with NL-17 cells | 0–250 mg/kg for 14 days | -Increase life span by decreasing tumor growth. | [184] |
| Blackberry | ||||
| In vitro | ||||
| Blackberry extract | HT-29 and HCT-116 cells | 25–200 µg/mL for 24 to 48 h | -Exert antiproliferative effects. | [145] |
| Anthocyanin-rich extracts from hull and crude blackberry | HT-29 cells | 13.6 to 49.2 µg of monomeric anthocyanins/mL for 48 to 72 h | -Induce significant antioxidant and antiproliferative activity. | [185] |
| Anthocyanin-rich extracts from crude blackberry | Caco-2 cells | 0.8, 1.6, 3.1, 6.3, 12.5 and 25 µg/mL for 24 h | -Inhibit peroxyl radical induced apoptosis. | [186] |
| In vivo | ||||
| Blackberry products | AOM induced Fisher 344 male | 50 g/kg for 17 weeks | -Inhibit colonic ACF formation. | [150] |
| Blackcurrant | ||||
| In vitro | ||||
| Black currant press residue extracts | Caco-2, HT-29, and HCT-116 cells | 0–125 μg GAE/mL for 24 to 48 h | -Suppress cancer cell proliferation. | [187] |
| Black currant extracts | HT-29 cells | 0.025% to 0.5% dry wt for 24 h | -Exert antiproliferative effect. | [142] |
| Methanol extracts of blackcurren | HT-29 cells | 0–60 mg/mL for 24 h | -Diminish cell proliferation via the p21WAF1 pathway. | [168] |
| IVD digestion and fecal fermentation | HT-29 and HT-115 cells | 0–50 µg/mL GAE for 24 h | -Exert anti-genotoxic, anti-mutagenic and anti-invasive activity. | [116] |
| Chokeberry | ||||
| In vitro | ||||
| In vitro gastric and pancreatic digestion of chokeberry juice | Caco-2 cells | 0 to 800 µM for 2 h a day for 4 days period | -Inhibit cell proliferation. -Arrest cell cycle at G2/M phase -Upregulate tumor suppressor CEACAM1 gene expresion. |
[125] |
| Anthocyanin-rich extracts | HT-29 cells | 0 to 200 μg/mL for 48 h | -Suppress cancer cell proliferation. | [153] |
| HT-29 cells | 10–75 µg of monomeric anthocyanin/mL for 24–72 h | -Inhibit cancer cell proliferation. | [154] | |
| HT-29 cells | 50 μg monomeric anthocyanin/mL for 24 h | -Inhibit cell proliferation. -Block the cell cycle and increase cell cycle regulatory protein. |
[188] | |
| In vivo | ||||
| Anthocyanin-rich extracts | AOM treated Fischer 344 male rats | 3.85 g of monomeric anthocyanin/kg for 14 weeks | -Inhibit colonic ACF formation. | [158] |
| Cloudberry | ||||
| In vitro | ||||
| Polyphenol-rich extracts | Caco-2 cells | 25, 50, and 75 μg of GAE/mL | -Inhibit cancer cell proliferation. | [162] |
| Methanolic extraction | HT-29 cells | 0–60 mg/mL for 24 to 48 h | -Disrupt cell proliferation. -Increases p21WAF1pathway. |
[168] |
| In vivo | ||||
| Freeze dried cloubberry | Apc Min/+ mouse | 1564 mg/kg for 10 weeks | -Inhibits the formation of intestinal adenoma. | [171] |
| Seabuckthorn | ||||
| In vitro | ||||
| Polyphenol rich extracts | HT-29 cells | 0.025%–0.5% dry wt for 24 h | -Inhibit cancer cell proliferation. | [142] |
| Isorhamnetin | HT-29, HCT-116 and SW480 cells | 0–80 μmol/L for 3 days | -Decreases cancer cell proliferation. -Inhibits signaling pathway and arrests cell cycle. |
[189] |
| In vivo | ||||
| Seabuckthorn seed oil | PhIP exposure Wistar rats | 2 to 8 mL/kg body wt for 12 to 36 h | -Improves oxidative stress and decreases abnormal cancer related gene expression. | [190] |
| Lingonberry | ||||
| In vitro | ||||
| Polyphenol-rich extracts | Caco-2 cells | 25, 50, and 75 μg of GAE/mL | -Induce antiproliferative activity. | [162] |
| Anthocyanin-rich extract | HT-29 cells | 0.025%–0.5% dry wt for 24 h | -Suppress the growth of cancer cells. | [142] |
| HT-29 cells | 0–60 mg/mL for 24 to 48 h | -Decrease cell proliferation proliferation via p21WAF1pathway. | [168] | |
| In vivo | ||||
| Freeze dried lingonberry | Apc Min/+ mouse | 1564 mg/kg for 10 weeks | -Decrease adenoma formation. | [171] |
| Barberry | ||||
| In vitro | ||||
| Berberine | SW480 cells | 5–50 µM for 12–72 h | -Suppresses cells growth. -Arrests cell cycle. -Induces apoptosis. -Inhibits angiogenesis and inflammation markers. |
[191] |
| Acai Berry | ||||
| In vitro | ||||
| Polyphenolic extracts | SW480, HT-29 and CCD-18Co cells | 5–20 mg/L for 48 h | -Suppress cells growth. -Show anti-inflammatory activity. |
[192] |
| In vivo | ||||
| Spray-dried acai powder | DMH in male Wistar rats | 2.5% or 5.0% acai power for 20 weeks | -Reduces the number of aberrant crypts, invasive tumors and tumor multiplicity. | [193] |
| Goji berry | ||||
| In vitro | ||||
| Lycium barbarum polysaccharides | SW480 and Caco-2 cells | 100–1000 mg/L for 1, 2, 3, 4,or 5 days | -Decreases cells growth by intrupting cell cycle. | [194] |
| Silverberry | ||||
| In vitro | ||||
| Extracts from seed and flesh of cherry silverberry | HT-29 cells | Seed extract (100–1600 g/mL) and flesh extract (200–3200 g/mL) for 48 h | -Exert anti-inflammation and anti-proliferation activities. | [195] |
| White currant | ||||
| In vivo | ||||
| Freeze dried white currant | Min mice | 10% for 10 weeks | -Prevents cancer initiation and progression. | [196] |
| Arctic bramble | ||||
| In vitro | ||||
| Polyphenol-rich extracts | Caco 2 cells | 25, 50, and 75 μg of GAE/mL | -Reduce cancer cell proliferation. | [162] |
| Elderberry | ||||
| In vitro | ||||
| Anthocyanin-rich extracts | HT-29 cells | 0 to 200 μg/mL for 48 h | -Inhibit cancer cell proliferation. | [153] |
| Jamun berry | ||||
| In vitro | ||||
| ETs rich jamun berry extracts | Human 293T cells | 10–1000 µg/mL for 48 h | -Exert chemopreventive activity. -Inhibit the canonical Wntsignaling pathway. |
[166] |
| Rosehip | ||||
| In vitro | ||||
| Polyphenol rich extracts | HT-29 cells | 0.025,0.05, 0.25, and 0.5% dry wt for 24 h | -Inhibit cancer cell proliferation. | [142] |
| 62.5–1000 g/L for 24 h | -Suppress cancer cell growth. | [93] | ||
| Emblic | ||||
| In vitro | ||||
| Ethanolic extracts | HT-29 cells | 10-100 μg/mL for 48 h | -Inhibit cancer cell proliferation. | [197] |
| Water extract | COLO320 cells | 0, 20, 40, 80, or 160 μg/mL PE for 24, 48, 72, or 96 h | -Suppress necrosis and delays mitotic progression. -Induce apoptosis. |
[198] |