原花青素在抗肿瘤机制中的研究进展
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摘要
原花青素是一种来源广泛的植物性治疗药物,既可用于日常饮食也可用做防治疾病。原花青素在肿瘤的防治中显示出明显的作用,本文对其抗肿瘤的各个分子机制,包括核因子κB(NF-κB)途径、促分裂原活化蛋白(MAPK)途径、磷脂酰肌醇3激酶/蛋白激酶B(PI3K/AKT)途径、细胞凋亡、调节基质金属蛋白酶、调节细胞周期等方面进行综述。
Proanthocyanidins are considered as the naturally available botanical which has been focused on consuming in individual's everyday diet but also been useful as a chemopreventive or chemotherapeutic agent for diseases. Especially for the tumors,proanthocyanidins play an important role in the prevention and treatment. This paper summarizes the latest developments on anti-tumor activities of proanthocyanidins from diffe-rent sources and their molecular targets,including nuclear factor-κB( NF-κB) pathway,mitogen-activated protein( MAPK) pathway,phosphatidylinositol-3 kinase/protein kinase B( PI3K/AKT) pathway,apoptosis,regulation of matrix metalloproteinase( MMP) and regulation of cell cycle.
Proanthocyanidins are considered as the naturally available botanical which has been focused on consuming in individual's everyday diet but also been useful as a chemopreventive or chemotherapeutic agent for diseases. Especially for the tumors,proanthocyanidins play an important role in the prevention and treatment. This paper summarizes the latest developments on anti-tumor activities of proanthocyanidins from diffe-rent sources and their molecular targets,including nuclear factor-κB( NF-κB) pathway,mitogen-activated protein( MAPK) pathway,phosphatidylinositol-3 kinase/protein kinase B( PI3K/AKT) pathway,apoptosis,regulation of matrix metalloproteinase( MMP) and regulation of cell cycle.
引文
[1] FRESQUET-CORRALES S,ROQUE E,SARRIóN-PERDIGONES A,et al. Metabolic engineering to simultaneously activate anthocyanin and proanthocyanidin biosynthetic pathways in Nicotiana spp[J/OL]. PLoS One,2017,12(9):e0184839. 2017-09-13[2019-02-21]. https://www. ncbi. nlm. nih. gov/pmc/articles/PMC5597232/.
[2]李聪,周玉涛,朱雪松,等.原花青素的提取分离及药理作用研究进展[J].国际中医中药杂志,2017,39(3):285-288.
[3] SUN W S, MENG J, WANG Z H, et al. Proanthocyanidins attenuation of H2O2-induced oxidative damage in tendon-derived stem cells via upregulating Nrf-2 signaling pathway[J/OL].Biomed Res Int,2017,2017:7529104. 2017-10-22[2019-02-21]. https://www. ncbi. nlm. nih. gov/pmc/articles/PMC5671684/.
[4] ARJAN J,PEIQIANG Y. The occurrence,biosynthesis,and molecular structure of proanthocyanidins and their effects on legume forage protein precipitation,digestion and absorption in the ruminant digestive tract[J]. Int J Mol Sci,2017,18(5):1105.
[5] YANG N G,GAO J,CHENG X,et al. Grape seed proanthocyanidins inhibit the proliferation,migration and invasion of tongue squamous cell carcinoma cells through suppressing the protein kinase B/nuclear factor-κB signaling pathway[J]. Int J Mol Med,2017,40(6):1881-1888.
[6] ALAAELDIN A H,GEHAN H H,HANAN M E,et al. Molecular characterization of the grape seeds extract’s effect against chemically induced liver cancer:In vivo and in vitro analyses[J]. Sci Rep,2018,8(1):1270.
[7] LI S,TAN H Y,WANG N,et al. The potential and action mechanism of polyphenols in the treatment of liver diseases[J/OL]. Oxid Med Cell Longev,2018,2018:8394818. 2018-02-04[2019-02-21]. https://www. ncbi. nlm. nih. gov/pubmed/29507653.
[8] LAURA A K,KATHERINE M W,BREE Z J,et al. Cranberry proanthocyanidins inhibit esophageal adenocarcinoma in vitro and in vivo through pleiotropic cell death induction and PI3K/AKT/m TOR inactivation[J]. Oncotarget,2015,6(32):33438-33455.
[9] LIU J,BAI J,JIANG G Q,et al. Anti-tumor effect of Pinus massoniana bark proanthocyanidins on ovarian cancer through induction of cell apoptosis and inhibition of cell migration[J/OL]. PLoS One,2015,10(11):e0142157. 2015-11-05[2019-02-21].https://www. ncbi. nlm. nih. gov/pmc/articles/PMC4634942/.
[10]王俊钢,杨丽,田君娜,等.原花青素对食管癌细胞增殖及糖酵解的影响及作用机制研究[J].癌症进展,2018,16(2):163-166.
[11] EVANGELOS G,BARBARA Z,SANDEEP D,et al. Mitochondrial permeabilisation engages NF-κB dependent anti-tumour activity under caspase deficiency[J]. Nat Cell Biol,2017,19(9):1116-1129.
[12] ELISA T. Molecular signaling mechanisms behind polyphenol-induced bone anabolism[J]. Phytochem Rev,2017,16(6):1183-1226.
[13]孙英殊,王雪峰,何丽霞,等.葡萄籽原花青素联合顺铂对喉癌细胞Hep-2生物学作用及机制研究[J].临床军医杂志,2017,45(2):176-179.
[14] MD N A,MUHAMMAD A,FAZLUL H. Polyphenols in colorectal cancer:Current state of knowledge including clinical trials and molecular mechanism of action[J/OL]. Biomed Res Int,2018,2018:4154185. 2018-01-15[2019-02-21]. https://www. ncbi. nlm. nih. gov/pmc/articles/PMC5820674/.
[15] AMEL B L,GENEVIVE L B,DANIEL G. Dual action of highbush blueberry proanthocyanidins on Aggregatibacter actinomycetemcomitans and the host inflammatory response[J]. BMC Complement Altern Med,2018,18(1):10.
[16]杨微,贺宝霞,张斌.松树皮原花青素对乳腺癌细胞增殖和转移作用[J].中国现代中药,2017,19(6):775-778.
[17]李海超,吕鹏,陈飞儿,等.原青花素的抗肿瘤机制研究现状[J].吉林医药学院学报,2017,38(1):64-66.
[18] PRASAD R,VAID M,KATIYAR S K. Grape proanthocyanidin inhibit pancreatic cancer cell growth in vitro and in vivo through induction of apoptosis and by targeting the PI3K/Akt pathway[J/OL].PLoS One,2012,7(8):e43064. 2012-08-08[2019-02-21]. https://www. ncbi. nlm. nih. gov/pubmed/22905202.
[19] MOKHTAR I Y,DINA K,HEBE M A. Neuro-and nephroprotective effect of grape seed proanthocyanidin extract against carboplatin and thalidomide through modulation of inflammation,tumor suppressor protein p53,neurotransmitters,oxidative stress and histology[J/OL]. Toxicol Rep,2018,5:568-578. 2018-04-30[2019-02-21]. http://europepmc. org/abstract/MED/29854627.
[20] WANG Y F,ALEX H,EVA C,et al. The cranberry flavonoids PAC DP-9 and quercetin aglycone induce cytotoxicity and cell cycle arrest and increase cisplatin sensitivity in ovarian cancer cells[J]. Int J Oncol,2015,46(5):1924-1934.
[2]李聪,周玉涛,朱雪松,等.原花青素的提取分离及药理作用研究进展[J].国际中医中药杂志,2017,39(3):285-288.
[3] SUN W S, MENG J, WANG Z H, et al. Proanthocyanidins attenuation of H2O2-induced oxidative damage in tendon-derived stem cells via upregulating Nrf-2 signaling pathway[J/OL].Biomed Res Int,2017,2017:7529104. 2017-10-22[2019-02-21]. https://www. ncbi. nlm. nih. gov/pmc/articles/PMC5671684/.
[4] ARJAN J,PEIQIANG Y. The occurrence,biosynthesis,and molecular structure of proanthocyanidins and their effects on legume forage protein precipitation,digestion and absorption in the ruminant digestive tract[J]. Int J Mol Sci,2017,18(5):1105.
[5] YANG N G,GAO J,CHENG X,et al. Grape seed proanthocyanidins inhibit the proliferation,migration and invasion of tongue squamous cell carcinoma cells through suppressing the protein kinase B/nuclear factor-κB signaling pathway[J]. Int J Mol Med,2017,40(6):1881-1888.
[6] ALAAELDIN A H,GEHAN H H,HANAN M E,et al. Molecular characterization of the grape seeds extract’s effect against chemically induced liver cancer:In vivo and in vitro analyses[J]. Sci Rep,2018,8(1):1270.
[7] LI S,TAN H Y,WANG N,et al. The potential and action mechanism of polyphenols in the treatment of liver diseases[J/OL]. Oxid Med Cell Longev,2018,2018:8394818. 2018-02-04[2019-02-21]. https://www. ncbi. nlm. nih. gov/pubmed/29507653.
[8] LAURA A K,KATHERINE M W,BREE Z J,et al. Cranberry proanthocyanidins inhibit esophageal adenocarcinoma in vitro and in vivo through pleiotropic cell death induction and PI3K/AKT/m TOR inactivation[J]. Oncotarget,2015,6(32):33438-33455.
[9] LIU J,BAI J,JIANG G Q,et al. Anti-tumor effect of Pinus massoniana bark proanthocyanidins on ovarian cancer through induction of cell apoptosis and inhibition of cell migration[J/OL]. PLoS One,2015,10(11):e0142157. 2015-11-05[2019-02-21].https://www. ncbi. nlm. nih. gov/pmc/articles/PMC4634942/.
[10]王俊钢,杨丽,田君娜,等.原花青素对食管癌细胞增殖及糖酵解的影响及作用机制研究[J].癌症进展,2018,16(2):163-166.
[11] EVANGELOS G,BARBARA Z,SANDEEP D,et al. Mitochondrial permeabilisation engages NF-κB dependent anti-tumour activity under caspase deficiency[J]. Nat Cell Biol,2017,19(9):1116-1129.
[12] ELISA T. Molecular signaling mechanisms behind polyphenol-induced bone anabolism[J]. Phytochem Rev,2017,16(6):1183-1226.
[13]孙英殊,王雪峰,何丽霞,等.葡萄籽原花青素联合顺铂对喉癌细胞Hep-2生物学作用及机制研究[J].临床军医杂志,2017,45(2):176-179.
[14] MD N A,MUHAMMAD A,FAZLUL H. Polyphenols in colorectal cancer:Current state of knowledge including clinical trials and molecular mechanism of action[J/OL]. Biomed Res Int,2018,2018:4154185. 2018-01-15[2019-02-21]. https://www. ncbi. nlm. nih. gov/pmc/articles/PMC5820674/.
[15] AMEL B L,GENEVIVE L B,DANIEL G. Dual action of highbush blueberry proanthocyanidins on Aggregatibacter actinomycetemcomitans and the host inflammatory response[J]. BMC Complement Altern Med,2018,18(1):10.
[16]杨微,贺宝霞,张斌.松树皮原花青素对乳腺癌细胞增殖和转移作用[J].中国现代中药,2017,19(6):775-778.
[17]李海超,吕鹏,陈飞儿,等.原青花素的抗肿瘤机制研究现状[J].吉林医药学院学报,2017,38(1):64-66.
[18] PRASAD R,VAID M,KATIYAR S K. Grape proanthocyanidin inhibit pancreatic cancer cell growth in vitro and in vivo through induction of apoptosis and by targeting the PI3K/Akt pathway[J/OL].PLoS One,2012,7(8):e43064. 2012-08-08[2019-02-21]. https://www. ncbi. nlm. nih. gov/pubmed/22905202.
[19] MOKHTAR I Y,DINA K,HEBE M A. Neuro-and nephroprotective effect of grape seed proanthocyanidin extract against carboplatin and thalidomide through modulation of inflammation,tumor suppressor protein p53,neurotransmitters,oxidative stress and histology[J/OL]. Toxicol Rep,2018,5:568-578. 2018-04-30[2019-02-21]. http://europepmc. org/abstract/MED/29854627.
[20] WANG Y F,ALEX H,EVA C,et al. The cranberry flavonoids PAC DP-9 and quercetin aglycone induce cytotoxicity and cell cycle arrest and increase cisplatin sensitivity in ovarian cancer cells[J]. Int J Oncol,2015,46(5):1924-1934.