Chemopreventive effect of apple and berry fruits against colon cancer

Table 1 In vitro and in vivo effects of apple extracts against colon cancer

Apple juice and itsComponents	Models(cell line/animal)	Observation/result	Ref.
Apple extracts	HT29 and LT97 colon adenoma cell line	SCFA increased 1.5 fold in fermented samples	[19]
		SCFA stimulates apoptosis, differentiation and growth arrest
Composite mixture of apple extracts	HT29 cells	PKC activity was decreased by 50% after 24 h exposure of 403 mg/mL	[17]
		Upstream signaling elements targeted after longer duration of exposure
Polyphenolic mixtures from cider, table apples and apple pomace; Phenolics such as phlorizin, rutin, quercetin and phloretin	Caco-2 cells and HT29 colonic cell lines	Reduced oxidative damage	[14]
		Reduced the presence of butyl hydroperoxide-induced ROS
	Caco-2 cells	Induction of p450 1A1 expression and inhibition of catalytic activity of the enzyme
Anthocyanidin-rich fraction of apple juice	HT29 and MCF-7 breast cancer cell line	Significant dose reduction in HT29 cells and not in MCF-7 cells	[15]
		MCF-7 cells are less responsive to extract exposure
Procyanidins of apple juice (polymeric polyphenols)	SW620 adenocarcinoma-derived metastatic cells of colon cancer	Dose-dependent inhibition of cell growth	[16]
		50% of inhibition at 45 mg/mL and total inhibition at 70 mg/mL
		Downregulation of signaling pathway such as cell proliferation and differentiation, PKC and enzymes involved in polyamine biosynthesis and stimulation of catabolism
		Increased number of apoptotic cells and interruption in cell cycle
Apple phytochemicals	Rats injected with azoxymethane	Reduction in preneoplastic lesions and 50% fewer aberrant crypts
Apple juice extract; Synthetic mixture, isolated components	HT29 cells	Decreased growth rate efficiently for 24, 48 and 72 h	[18]
		Increased the expression of genes which include phase-2 enzymes, including glutathone-s-transferases and sulfotransferases, which are involved in chemoprevention
		Growth rate inhibition was less efficient comparatively
		Lesser effectiveness than either mixture
Two preparation methods of apple juice: clear and cloudy (higher content of pectin and procyanidin)	Rat model (induced with 1,2-dimethylhydrazine)	Protection from dimethylhydrazine-induced genotoxic damage	[20]
		Important markers were reduced including decreased number of large aberrant crypt foci in the distal colon, reduced DNA damage and reduced hyper-proliferation
Polyphenolic-rich extracts	Rat model (induced with 1,2-dimethylhydrazine)	Juice fractions were found to be more effective in protecting from damage compared to isolated fractions	[21]

PKC: Protein kinase C; ROS: Reactive oxygen species; SCFA: Short-chain fatty acids.

Table 2 In vitro and in vivo effects of berry extracts against colon cancer

Berry juice and itsComponents	Models(cell line/animal)	Observation/result	Ref.
Anthocyanin fractions of berry juice	HCT-15 cells	Inhibited growth of human intestinal carcinoma cells	[31,33]
	HCT-116 cells	Inhibited the growth of colon cancer cells
Chokeberry ARE	HT29 cells	Percentage of cells increased and blockade in G1/G0 phase of cell cycle	[32,33]
		Increased expression of p21WAF1 and p27KIP1 genes
		Decreased percentage of cells in S phase indicating that cells moved to G2/M phase	[35]
Predominant anthocyanin: cyanidin-3-galactoside	HT29 cells	65% growth inhibition after 24 h exposure	[34]
		High cell viability observed indicating cytostatic inhibition
		Inactivation of COX-1 and COX-2 enzymes
Anthocyanins (cyanidin-3-glucosylrutinoside and cyanidin-3-rutinoside)	HT29 cells	Growth inhibition of cells may occur in a COX-independent manner	[37]
Phytochemicals of berry juice; Carotenoid (β-carotene) and flavonoid (tangeritin)	HT29 cells	Upregulation of p21WAF1 and p27KIP1 expression	[35]
		p21WAF1 CDKI blocks G1 and G2 phase cyclin-CDK complexes
Anthocyanin-rich purple corn color of berry juice	Rats injected with PhIP	Decrease in incidence of early colon cancer lesions, decrease in aberrant crypt foci and a protective effect against PhIP-induced colon carcinogenesis	[33]
Anthocyanin-rich black raspberries	Rodents with colorectal cancer/polyp tissue	Biomarkers of proliferation and angiogenesis were significantly reduced while apoptosis of cancer cells was enhanced
Mirtocyan of bilberry extract	Patients with colorectal adenocarcinoma and colorectal liver metastases	Significant reduction in IGF-1 levels thereby reducing carcinogenesis	[40]

ARE: Anthocyanin-rich extract; CDK: Cyclin-dependent kinase; CDKI: CDK inhibitor; COX: Cyclooxygenase; IGF-1: Insulin-like growth factor-1; PhIP: 2-amino-1-methyl-6-phenylimidazol(4,5-b) pyridine.