花青素抗消化道肿瘤的作用机制研究进展
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摘要
消化道恶性肿瘤的发病率和死亡率均居世界前列。花青素属于酚类化合物中的黄酮类化合物,具有抗氧、抗炎、抗肿瘤、预防心血管疾病等活性。通过对花青素以往的研究,从抗氧化、抗炎、阻滞细胞周期、促进肿瘤细胞凋亡及抑制肿瘤转移和血管生成等方面对其在抗肿瘤领域的进展进行综述。
The morbidity and mortality of digestive tract malignant tumors rank the highest in the world.Anthocyanins are a class of flavonoids which belong to the phenolic group and show some activities such as antioxidant, anti-inflammation, antitumor, and prevention of cardiovascular disease. Based on the previous studies of anthocyanins, the antitumor mechanisms of anthocyanins were reviewed from the aspects of antioxidant, antiinflammation, inducing cell cycle arrest, stimulating apoptosis of tumor cells, inhibition of tumor metastasis and angiogenesis.
The morbidity and mortality of digestive tract malignant tumors rank the highest in the world.Anthocyanins are a class of flavonoids which belong to the phenolic group and show some activities such as antioxidant, anti-inflammation, antitumor, and prevention of cardiovascular disease. Based on the previous studies of anthocyanins, the antitumor mechanisms of anthocyanins were reviewed from the aspects of antioxidant, antiinflammation, inducing cell cycle arrest, stimulating apoptosis of tumor cells, inhibition of tumor metastasis and angiogenesis.
引文
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[2]罗晓玲,徐嘉红,杨武斌,等.蓝莓花色苷抗氧化功能及稳定性研究进展.食品工业科技,2018,39:312-7
[3]Mueller D,Jung K,Winter M,et al.Human intervention study to investigate the intestinal accessibility and bioavailability of anthocyanins from bilberries.Food Chem,2017,231:275-86
[4]Wu X,Prior R L.Systematic identification and characterization of anthocyanins by HPLC-ESI-MS/MS in common foods in the United States:Fruits and berries.JAgric Food Chem,2005,53:2589-99
[5]He XQ,Han KQ.Key component of inflammatory microenvironment and tumor.Int J Oncol,2014,41:169-72
[6]Gorlach S,Fichna J,Lewandowska U.Polyphenols as mitochondria-targeted anticancer drugs.Cancer Lett,2015,366:141-9
[7]Li D,Wang P,Luo Y,et al.Health benefits of anthocyanins and molecular mechanisms:update from recent decade.Crit Rev Food Sci Nutr,2017,57:1729-41
[8]Hariri BM,Mcmahon DB,Chen B,et al.Flavones modulate respiratory epithelial innate immunity:antiinflammatory effects and activation of T2R14 receptor.JBiol Chem,2017,292:8484-97
[9]Fantini M,Benvenuto M,Masuelli L.In vitro and in vivo antitumoral effects of combinations of polyphenols,or polyphenols and anticancer drugs:perspectives on cancer treatment.Int J Mol Sci,2015,16:9236-82
[10]Xiao D,Sandhu A,Huang Y,et al.The effect of dietary factors on strawberry anthocyanins oral bioavailability.Food Funct,2017,8:3970-9
[11]Oghumu S,Casto BC,Ahn-Jarvis J,et al.Inhibition of Pro-inflammatory and anti-apoptotic biomarkers during experimental oral cancer chemoprevention by dietary black raspberries.Front Immunol,2017,8:1325
[12]Baba AB,Kowshik J,Krishnaraj J,et al.Blueberry inhibits invasion and angiogenesis in 7,12-dimethylbenz[a]anthracene(DMBA)-induced oral squamous cell carcinogenesis in hamsters via suppression of TGF-βand NF-κB signaling pathways.J Nutr Biochem,2016,35:37-47
[13]Reen RK,Nines R,Stoner GD.Modulation of N-nitrosomethylbenzylamine metabolism by black raspberries in the esophagus and liver of Fischer 344 rats.Nutr Cancer,2006,54:47-57
[14]Peiffer DS,Zimmerman NP,Wang LS,et al.Chemoprevention of esophageal cancer with black raspberries,their component anthocyanins,and a major anthocyanin metabolite,protocatechuic acid.Cancer Prev Res,2014,7:574-84
[15]Peiffer DS,Wang LS,Zimmerman NP,et al.Dietary consumption of black raspberries or their anthocyanin constituents alters innate immune cell trafficking in esophageal cancer.Cancer Immunol Res,2016,4:72-82
[16]Shi N,Riedl KM,Schwartz SJ,et al.Efficacy comparison of lyophilised black raspberries and combination of celecoxib and PBIT in prevention of carcinogen-induced oesophageal cancer in rats.J Funct Foods,2016,27:84-94
[17]Petrick JL,Steck SE,Bradshaw PT,et al.Dietary intake of flavonoids and oesophageal and gastric cancer:incidence and survival in the United States of America(USA).Br J Cancer,2015,112:1291-300
[18]Sugata M,Lin CY,Shih YC.Anti-inflammatory and anticancer activities of taiwanese purple-fleshed sweet potatoes(Ipomoea batatas L.Lam)extracts.Biomed Res Int,2015,2015:768093
[19]Lu JN,Lee WS,Nagappan A,et al.Anthocyanins from the fruit of Vitiscoignetiae Pulliat potentiate the cisplatin activity by inhibiting PI3K/Akt signaling pathways in human gastric cancer cells.J Cancer Prev,2015,20:50-6
[20]Pan P,Kang S,Wang Y,et al.Black raspberries enhance natural killer cell infiltration into the colon and suppress the progression of colorectal cancer.Front Immunol,2017,8:997
[21]Shin DY,Lu JN,Kim GY,et al.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,2011,25:567-72
[22]陈琦,李少伟,贾宇臣,等.p53在蓝莓花青素诱导Lovo细胞凋亡中的作用.生物技术,2014,24:34-8
[23]Mazewski C,Liang K,Gonzalez EDM.Comparison of the effect of chemical composition of anthocyanin-rich plant extracts on colon cancer cell proliferation and their potential mechanism of action using in vitro,in silico,and biochemical assays.Food Chem,2018,242:378-88
[24]Fernández J,García L,Monte J,et al.Functional anthocyanin-rich sausages diminish colorectal cancer in an animal model and reduce pro-inflammatory bacteria in the intestinal microbiota.Genes,2018,9:133
[25]徐春明,庞高阳,李婷.花青素的生理活性研究进展.中国食品添加剂,2013,3:205-10
[26]Higgins JA,Zainol M,Brown K,et al.Anthocyans as tertiary chemopreventive agents in bladder cancer:antioxidant mechanisms and interaction with mitomycin C.Mutagenesis,2014,29:227-35
[27]Alvarez-Suarez JM,Dragana D,Slavica R,et al.Strawberry polyphenols attenuate ethanol-induced gastric lesions in rats by activation of antioxidant enzymes and attenuation of MDA increase.PLoS One,2011,6:e25878
[28]Sousa A,Araujo P,Azevedo J,et al.Antioxidant and antiproliferative properties of 3-deoxyanthocyanidins.Food Chem,2016,192:142-8
[29]Shih PH,Yeh CT,Yen GC.Anthocyanins induce the activation of phase II enzymes through the antioxidant response element pathway against oxidative stress-induced apoptosis.J Agric Food Chem,2007,55:9427-35
[30]Knobloch TJ,Uhrig LK,Pearl DK,et al.Suppression of pro-inflammatory and pro-survival biomarkers in oral cancer patients consuming a black raspberry phytochemicalrich troche.Cancer Prev Res,2016,9:159-71
[31]Kim JM,Kim KM,Park EH,et al.Anthocyanins from black soybean inhibit Helicobacter pylori-induced inflammation in human gastric epithelial AGS cells.Microbiol Immunol,2013,57:366-73
[32]Medda R,Lyros O,Schmidt JL,et al.Anti inflammatory and anti angiogenic effect of black raspberry extract on human esophagea land intestinal microvascular endothelial cells.Microvasc Res,2015,97:167-80
[33]Sofia R,Spalinger MR,Claudia G,et al.Bilberry-derived anthocyanins modulate cytokine expression in the intestine of patients with ulcerative colitis.PLoS One,2016,11:e0154817
[34]Chen L,Jiang B,Zhong C,et al.Chemoprevention of colorectal cancer by black raspberry anthocyanins involved the modulation of gut microbiota and SFRP2demethylation.Carcinogenesis,2018,39:471-81
[35]Baba AB,Nivetha R,Indranil C,et al.Blueberry and malvidin inhibit cell cycle progression and induce mitochondrial-mediated apoptosis by abrogating the JAK/STAT-3 signalling pathway.Food Chem Toxicol,2017,109:534-43
[36]陈琦,李少伟,贾宇臣,等.蓝莓花青素通过下调p53基因DNA甲基化抑制口腔癌KB细胞增殖及诱导细胞凋亡.遗传,2014,36:566-73
[37]刘春远,赵豹猛,蒋宏,等.黑米花青素对结肠癌细胞增殖、细胞周期及凋亡的影响.中华结直肠疾病电子杂志,2014,3:42-4
[38]Wang Y,Zhang XN,Xie WH,et al.The growth of SGC-7901 tumor xenografts was suppressed by Chinese bayberry anthocyanin extract through upregulating KLF6gene expression.Nutrients,2016,8:599
[39]侯锐,王利,李少伟,等.蓝莓花青素诱导结肠癌LS174T细胞凋亡和抑制其增殖.基础医学与临床,2016,36:1467-71
[40]Charepalli V,Reddivari L,Radhakrishnan S,et al.Anthocyanin-containing purple-fleshed potatoes suppress colon tumorigenesis via elimination of colon cancer stem cells.J Nutr Biochem,2015,26:1641-9
[41]Charepalli V,Reddivari L,Vadde R,et al.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,2016,8:29
[42]Huang HP,Chang YC,Wu CH,et al.Anthocyanin-rich Mulberry,extract inhibit the gastric cancer cell growth in vitro,and xenograft mice by inducing signals of p38/p53and c-jun.Food Chem,2011,129:1703-9
[43]Fan MJ,Wang IC,Hsiao YT,et al.Anthocyanins from black rice(Oryza sativa L.)demonstrate antimetastatic properties by reducing MMPs and NF-κB expressions in human oral cancer CAL 27 cells.Nutr Cancer,2015,67:327-38
[44]Wang LS,Kuo CT,Cho SJ,et al.black raspberry-derived anthocyanins demethylate tumor suppressor genes through the inhibition of DNMT1 and DNMT3B in colon cancer cells.Nutr Cancer,2013,65:118-25
[45]Mazewski C,Liang K,Mejia EGD.Inhibitory potential of anthocyanin-rich purple and red corn extracts on human colorectal cancer cell proliferation in vitro.J Funct Foods,2017,34:254-65
[46]Wang LS,Hecht SS,Carmella SG,et al.Anthocyanins in black raspberries prevent esophageal tumors in rats.Cancer Prev Res,2009,2:84-93
[47]Forester SC,Choy YY,Waterhouse AL,et al.The anthocyanin metabolites gallic acid,3-O-methylgallic acid,and 2,4,6-trihydroxybenzaldehyde decrease human colon cancer cell viability by regulating pro-oncogenic signals.Mol Carcinog,2014,53:432-9
[2]罗晓玲,徐嘉红,杨武斌,等.蓝莓花色苷抗氧化功能及稳定性研究进展.食品工业科技,2018,39:312-7
[3]Mueller D,Jung K,Winter M,et al.Human intervention study to investigate the intestinal accessibility and bioavailability of anthocyanins from bilberries.Food Chem,2017,231:275-86
[4]Wu X,Prior R L.Systematic identification and characterization of anthocyanins by HPLC-ESI-MS/MS in common foods in the United States:Fruits and berries.JAgric Food Chem,2005,53:2589-99
[5]He XQ,Han KQ.Key component of inflammatory microenvironment and tumor.Int J Oncol,2014,41:169-72
[6]Gorlach S,Fichna J,Lewandowska U.Polyphenols as mitochondria-targeted anticancer drugs.Cancer Lett,2015,366:141-9
[7]Li D,Wang P,Luo Y,et al.Health benefits of anthocyanins and molecular mechanisms:update from recent decade.Crit Rev Food Sci Nutr,2017,57:1729-41
[8]Hariri BM,Mcmahon DB,Chen B,et al.Flavones modulate respiratory epithelial innate immunity:antiinflammatory effects and activation of T2R14 receptor.JBiol Chem,2017,292:8484-97
[9]Fantini M,Benvenuto M,Masuelli L.In vitro and in vivo antitumoral effects of combinations of polyphenols,or polyphenols and anticancer drugs:perspectives on cancer treatment.Int J Mol Sci,2015,16:9236-82
[10]Xiao D,Sandhu A,Huang Y,et al.The effect of dietary factors on strawberry anthocyanins oral bioavailability.Food Funct,2017,8:3970-9
[11]Oghumu S,Casto BC,Ahn-Jarvis J,et al.Inhibition of Pro-inflammatory and anti-apoptotic biomarkers during experimental oral cancer chemoprevention by dietary black raspberries.Front Immunol,2017,8:1325
[12]Baba AB,Kowshik J,Krishnaraj J,et al.Blueberry inhibits invasion and angiogenesis in 7,12-dimethylbenz[a]anthracene(DMBA)-induced oral squamous cell carcinogenesis in hamsters via suppression of TGF-βand NF-κB signaling pathways.J Nutr Biochem,2016,35:37-47
[13]Reen RK,Nines R,Stoner GD.Modulation of N-nitrosomethylbenzylamine metabolism by black raspberries in the esophagus and liver of Fischer 344 rats.Nutr Cancer,2006,54:47-57
[14]Peiffer DS,Zimmerman NP,Wang LS,et al.Chemoprevention of esophageal cancer with black raspberries,their component anthocyanins,and a major anthocyanin metabolite,protocatechuic acid.Cancer Prev Res,2014,7:574-84
[15]Peiffer DS,Wang LS,Zimmerman NP,et al.Dietary consumption of black raspberries or their anthocyanin constituents alters innate immune cell trafficking in esophageal cancer.Cancer Immunol Res,2016,4:72-82
[16]Shi N,Riedl KM,Schwartz SJ,et al.Efficacy comparison of lyophilised black raspberries and combination of celecoxib and PBIT in prevention of carcinogen-induced oesophageal cancer in rats.J Funct Foods,2016,27:84-94
[17]Petrick JL,Steck SE,Bradshaw PT,et al.Dietary intake of flavonoids and oesophageal and gastric cancer:incidence and survival in the United States of America(USA).Br J Cancer,2015,112:1291-300
[18]Sugata M,Lin CY,Shih YC.Anti-inflammatory and anticancer activities of taiwanese purple-fleshed sweet potatoes(Ipomoea batatas L.Lam)extracts.Biomed Res Int,2015,2015:768093
[19]Lu JN,Lee WS,Nagappan A,et al.Anthocyanins from the fruit of Vitiscoignetiae Pulliat potentiate the cisplatin activity by inhibiting PI3K/Akt signaling pathways in human gastric cancer cells.J Cancer Prev,2015,20:50-6
[20]Pan P,Kang S,Wang Y,et al.Black raspberries enhance natural killer cell infiltration into the colon and suppress the progression of colorectal cancer.Front Immunol,2017,8:997
[21]Shin DY,Lu JN,Kim GY,et al.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,2011,25:567-72
[22]陈琦,李少伟,贾宇臣,等.p53在蓝莓花青素诱导Lovo细胞凋亡中的作用.生物技术,2014,24:34-8
[23]Mazewski C,Liang K,Gonzalez EDM.Comparison of the effect of chemical composition of anthocyanin-rich plant extracts on colon cancer cell proliferation and their potential mechanism of action using in vitro,in silico,and biochemical assays.Food Chem,2018,242:378-88
[24]Fernández J,García L,Monte J,et al.Functional anthocyanin-rich sausages diminish colorectal cancer in an animal model and reduce pro-inflammatory bacteria in the intestinal microbiota.Genes,2018,9:133
[25]徐春明,庞高阳,李婷.花青素的生理活性研究进展.中国食品添加剂,2013,3:205-10
[26]Higgins JA,Zainol M,Brown K,et al.Anthocyans as tertiary chemopreventive agents in bladder cancer:antioxidant mechanisms and interaction with mitomycin C.Mutagenesis,2014,29:227-35
[27]Alvarez-Suarez JM,Dragana D,Slavica R,et al.Strawberry polyphenols attenuate ethanol-induced gastric lesions in rats by activation of antioxidant enzymes and attenuation of MDA increase.PLoS One,2011,6:e25878
[28]Sousa A,Araujo P,Azevedo J,et al.Antioxidant and antiproliferative properties of 3-deoxyanthocyanidins.Food Chem,2016,192:142-8
[29]Shih PH,Yeh CT,Yen GC.Anthocyanins induce the activation of phase II enzymes through the antioxidant response element pathway against oxidative stress-induced apoptosis.J Agric Food Chem,2007,55:9427-35
[30]Knobloch TJ,Uhrig LK,Pearl DK,et al.Suppression of pro-inflammatory and pro-survival biomarkers in oral cancer patients consuming a black raspberry phytochemicalrich troche.Cancer Prev Res,2016,9:159-71
[31]Kim JM,Kim KM,Park EH,et al.Anthocyanins from black soybean inhibit Helicobacter pylori-induced inflammation in human gastric epithelial AGS cells.Microbiol Immunol,2013,57:366-73
[32]Medda R,Lyros O,Schmidt JL,et al.Anti inflammatory and anti angiogenic effect of black raspberry extract on human esophagea land intestinal microvascular endothelial cells.Microvasc Res,2015,97:167-80
[33]Sofia R,Spalinger MR,Claudia G,et al.Bilberry-derived anthocyanins modulate cytokine expression in the intestine of patients with ulcerative colitis.PLoS One,2016,11:e0154817
[34]Chen L,Jiang B,Zhong C,et al.Chemoprevention of colorectal cancer by black raspberry anthocyanins involved the modulation of gut microbiota and SFRP2demethylation.Carcinogenesis,2018,39:471-81
[35]Baba AB,Nivetha R,Indranil C,et al.Blueberry and malvidin inhibit cell cycle progression and induce mitochondrial-mediated apoptosis by abrogating the JAK/STAT-3 signalling pathway.Food Chem Toxicol,2017,109:534-43
[36]陈琦,李少伟,贾宇臣,等.蓝莓花青素通过下调p53基因DNA甲基化抑制口腔癌KB细胞增殖及诱导细胞凋亡.遗传,2014,36:566-73
[37]刘春远,赵豹猛,蒋宏,等.黑米花青素对结肠癌细胞增殖、细胞周期及凋亡的影响.中华结直肠疾病电子杂志,2014,3:42-4
[38]Wang Y,Zhang XN,Xie WH,et al.The growth of SGC-7901 tumor xenografts was suppressed by Chinese bayberry anthocyanin extract through upregulating KLF6gene expression.Nutrients,2016,8:599
[39]侯锐,王利,李少伟,等.蓝莓花青素诱导结肠癌LS174T细胞凋亡和抑制其增殖.基础医学与临床,2016,36:1467-71
[40]Charepalli V,Reddivari L,Radhakrishnan S,et al.Anthocyanin-containing purple-fleshed potatoes suppress colon tumorigenesis via elimination of colon cancer stem cells.J Nutr Biochem,2015,26:1641-9
[41]Charepalli V,Reddivari L,Vadde R,et al.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,2016,8:29
[42]Huang HP,Chang YC,Wu CH,et al.Anthocyanin-rich Mulberry,extract inhibit the gastric cancer cell growth in vitro,and xenograft mice by inducing signals of p38/p53and c-jun.Food Chem,2011,129:1703-9
[43]Fan MJ,Wang IC,Hsiao YT,et al.Anthocyanins from black rice(Oryza sativa L.)demonstrate antimetastatic properties by reducing MMPs and NF-κB expressions in human oral cancer CAL 27 cells.Nutr Cancer,2015,67:327-38
[44]Wang LS,Kuo CT,Cho SJ,et al.black raspberry-derived anthocyanins demethylate tumor suppressor genes through the inhibition of DNMT1 and DNMT3B in colon cancer cells.Nutr Cancer,2013,65:118-25
[45]Mazewski C,Liang K,Mejia EGD.Inhibitory potential of anthocyanin-rich purple and red corn extracts on human colorectal cancer cell proliferation in vitro.J Funct Foods,2017,34:254-65
[46]Wang LS,Hecht SS,Carmella SG,et al.Anthocyanins in black raspberries prevent esophageal tumors in rats.Cancer Prev Res,2009,2:84-93
[47]Forester SC,Choy YY,Waterhouse AL,et al.The anthocyanin metabolites gallic acid,3-O-methylgallic acid,and 2,4,6-trihydroxybenzaldehyde decrease human colon cancer cell viability by regulating pro-oncogenic signals.Mol Carcinog,2014,53:432-9