芹菜素抗肿瘤机制的研究进展
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摘要
芹菜素是一种天然的黄酮类化合物,广泛存在于多种水果、蔬菜和草药中,具有抗肿瘤、抗氧化、抗炎等多种生物学作用。芹菜素在抗肿瘤方面效果显著,可抑制肿瘤细胞增殖、诱导肿瘤细胞凋亡、抑制肿瘤侵袭和转移、干扰肿瘤细胞的信号转导、逆转细胞耐药性,提高化疗药物敏感性和抗氧化作用等。本文综述了芹菜素主要的生物学作用及抗肿瘤作用机制,并展望了芹菜素的应用开发前景。
Apigenin is a natural flavonoid compound that is widely found in various fruits, vegetables and herbs, and has various biological effects such as anti-tumor, anti-oxidation and anti-inflammatory. Apigenin has significant anti-tumor effects, which can inhibit tumor cell proliferation, induce apoptosis of tumor cells, inhibit tumor invasion and metastasis, interfere with signal transduction of tumor cells, reverse drug resistance of cells, increase the sensitivity of chemotherapeutic drugs and anti-oxidation, etc. This review summarizes the main biological effects of apigenin and its anti-tumor mechanisms, and looks forward to the prospects of application and development of apigenin.
Apigenin is a natural flavonoid compound that is widely found in various fruits, vegetables and herbs, and has various biological effects such as anti-tumor, anti-oxidation and anti-inflammatory. Apigenin has significant anti-tumor effects, which can inhibit tumor cell proliferation, induce apoptosis of tumor cells, inhibit tumor invasion and metastasis, interfere with signal transduction of tumor cells, reverse drug resistance of cells, increase the sensitivity of chemotherapeutic drugs and anti-oxidation, etc. This review summarizes the main biological effects of apigenin and its anti-tumor mechanisms, and looks forward to the prospects of application and development of apigenin.
引文
[1]SHUKLA S,GUPTA S,SARKAR F H.Apigenin:a promising molecule for cancer prevention[J].Pharm Res,2010,27(6):962-978.
[2]DOU X J,ZHOU Z Q,XIE D F.Research progress on the biological activity of apigenin[J].Technol Wind(科技风),2018(4):171.
[3]CHEN N,YE L H.Mechanism of apigenin’s inhibition of cancer cell proliferation:review of progress[J].Global Tradit Chin Med(环球中医药),2014,7(2):151-154.
[4]WU D G,YU P,LI J W,et al.Apigenin potentiates the growth inhibitory effects by IKK-β-mediated NF-κB activation in pancreatic cancer cells[J].Toxicol Lett,2014,224(1):157-164.
[5]SHUKLA S,KANWAL R,SHANKAR E,et al.Apigenin blocks IKKαactivation and suppresses prostate cancer progression[J].Oncotarget,2015,6(31):31216-31232.
[6]SUNG B,CHUNG H Y,KIM N D.Role of apigenin in cancer prevention via the induction of apoptosis and autophagy[J].JCancer Prev,2016,21(4):216-226.
[7]XU X X,SHI L,ZHANG S G,et al.Apigenin inhibits human glioma SHG-44 cells growth and induces apoptosis[J].Jiangsu Med J(江苏医药),2016,42(22):2421-2424.
[8]SUBHASITANONT P,CHOKCHAICHAMNANKIT D,CHIABLAEM K,et al.Apigenin inhibits growth and induces apoptosis in human cholangiocarcinoma cells[J].Oncol Lett,2017,14(4):4361-4371.
[9]QIN Y,ZHAO D,ZHOU H G,et al.Apigenin inhibits NF-κBand Snail signaling,EMT and metastasis in human hepatocellular carcinoma[J].Oncotarget,2016,7(27):41421-41431.
[10]MIN X U,WANG S,SONG Y U,et al.Apigenin suppresses colorectal cancer cell proliferation,migration and invasion via inhibition of the Wnt/β-catenin signaling pathway[J].Oncol Lett,2016,11(5):3075-3080.
[11]WANG L,KUANG L,HITRON J A,et al.Apigenin suppresses migration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4expression[J].Toxicol Appl Pharmacol,2013,272(1):108-116.
[12]LI R B,YANG J S.Inhibitory effect of apigenin against migration and invasion of human lung cancer A549 cells and the related mechanism[J].Acad J Second Military Med Univ(第二军医大学学报),2015,36(8):878-882.
[13]ZHANG J Z,MA D L,ZHANG S H,et al.Effects of apigenin on the invasion ability of ovarian cancer cells by regulating Wnt signaling pathway[J].Anti-Tumor Pharmacy(肿瘤药学),2017,7(3):284-289.
[14]AMADO N G,PREDES D,MORENO M M,et al.Flavonoids and Wnt/β-catenin signaling:Potential role in colorectal cancer therapies[J].Int J Molecul Sci,2014,15(7):12094-12106.
[15]VILCHEZ V,TURCIOS L,MARTI F,et al.Targeting Wnt/β-catenin pathway in hepatocellular carcinoma treatment[J].World J Gastroenterol,2016,22(2):823-832.
[16]MOHAMMED M K,SHAO C,WANG J,et al.Wnt/β-catenin signaling plays an ever-expanding role in stem cell self-renewal,tumorigenesis and cancer chemoresistance[J].Gene Dis,2016,3(1):11-40.
[17]LIAO Y,SHEN W,KONG G,et al.Apigenin induces the apoptosis and regulates MAPK signaling pathways in mouse macrophage ANA-1 cells[J].Plos One,2014,9(3):e92007.
[18]KIM A,LEE C S.Apigenin reduces the Toll-like receptor-4-dependent activation of NF-?B by suppressing the Akt,m TOR,JNK,and p38-MAPK[J].Naunyn Schmiedebergs Arch Pharmacol,2018,391(3):271-283.
[19]LOW H B,ZHANG Y.Regulatory roles of mapk phosphatases in cancer[J].Immune Network,2016,16(2):85-98.
[20]KIM E K,CHOI E J.Compromised MAPK signaling in human diseases:an update[J].Arch Toxicol,2015,89(6):867-882.
[21]LU X,LI Y,LI X,et al.Luteolin induces apoptosis in vitro through suppressing the MAPK and PI3K signaling pathways in gastric cancer[J].Oncol Lett,2017,14(2):1993-2000.
[22]SURESH S,IRVINE A E.The NOTCH signaling pathway in normal andmalignant blood cell production[J].J Cell Commun Signal,2015,9(1):5-13.
[23]KIM B,STEPHEN S L,HANBY A M,et al.Chemotherapy induces Notch1-dependent MRP1 up-regulation,inhibition of which sensitizes breast cancer cells to chemotherapy[J].BMCCancer,2015,15(1):1-12.
[24]SHI F T,YU M,ZLOTY D,et al.Notch signaling is significantly suppressed in basal cell carcinomas and activation induces basal cell carcinoma cell apoptosis[J].Mol Med Rep,2017,15(4):1441-1454.
[25]FAN H,PAIBOONRUNGRUAN C,ZHANG X,et al.Nrf2regulates cellular behaviors and Notch signaling in oral squamous cell carcinoma cells[J].Biochem Biophys Res Commun,2017,493(1):833-839.
[26]LIN C H,CHANG C Y,LEE K R,et al.Flavones inhibit breast cancer proliferation through the Akt/FOXO3a signaling pathway[J].Bmc Cancer,2015,15(1):1-12.
[27]ERDOGAN S,DOGANLAR O,DOGANLAR Z B,et al.The flavonoid apigenin reduces prostate cancer CD44(+)stem cell survival and migration through PI3K/Akt/NF-κB signaling[J].Life Sci,2016(162):77-86
[28]邢海军,崔海燕,赵建虎.芹菜素通过下调MDR-1/P-gp表达逆转结肠癌耐药细胞HCT-8/5FU多药耐药性的作用及机制[J].中国老年学,2014(13):3709-3712.
[29]ERDOGAN S,TURKEKUL K,SERTTAS R,et al.The natural flavonoid apigenin sensitizes human CD44+prostate cancer stem cells to cisplatin therapy[J].Biomed Pharmacotherapy,2017,88(2017):210-217.
[30]ZHAO Y X,LIU J F,JIANG M H,et al.Effect of apigenin on the multidrug resistant breast cancer cell line MCF-7/ADR[J].China Oncol(中国癌症杂志),2017,27(8):648-654.
[31]SUH K S,OH S,WOO J T,et al.Apigenin attenuates2-deoxy-D-ribose-induced oxidative cell damage in HIT-T15pancreaticβ-cells[J].Biol Pharm Bull,2012,35(1):121-126.
[32]SINGH J P,SELVENDIRAN K,BANU S M,et al.Protective role of Apigenin on the status of lipid peroxidation and antioxidant defense against hepatocarcinogenesis in Wistar albino rats[J].Phytomedicine,2004,11(4):309-314.
[33]HU J,LI Z,XU L T,et al.Protective effect of apigenin on ischemia/reperfusion injury of the isolated rat heart[J].Cardiovasc Toxicol,2015,15(3):241-249.
[34]LI Z F.Research progress in antitumor effect and its mechanism of apigenin[J].J Dis Monitor Control(疾病监测与控制),2013,7(10):616-618.
[35]HONG J,FRISTIOHADY A,NGUYEN C H,et al.Apigenin and luteolin attenuate the breaching of MDA-MB231 breast cancer spheroids through the lymph endothelial barrier in vitro[J].Front Pharmacol,2018(9):1-10.
[2]DOU X J,ZHOU Z Q,XIE D F.Research progress on the biological activity of apigenin[J].Technol Wind(科技风),2018(4):171.
[3]CHEN N,YE L H.Mechanism of apigenin’s inhibition of cancer cell proliferation:review of progress[J].Global Tradit Chin Med(环球中医药),2014,7(2):151-154.
[4]WU D G,YU P,LI J W,et al.Apigenin potentiates the growth inhibitory effects by IKK-β-mediated NF-κB activation in pancreatic cancer cells[J].Toxicol Lett,2014,224(1):157-164.
[5]SHUKLA S,KANWAL R,SHANKAR E,et al.Apigenin blocks IKKαactivation and suppresses prostate cancer progression[J].Oncotarget,2015,6(31):31216-31232.
[6]SUNG B,CHUNG H Y,KIM N D.Role of apigenin in cancer prevention via the induction of apoptosis and autophagy[J].JCancer Prev,2016,21(4):216-226.
[7]XU X X,SHI L,ZHANG S G,et al.Apigenin inhibits human glioma SHG-44 cells growth and induces apoptosis[J].Jiangsu Med J(江苏医药),2016,42(22):2421-2424.
[8]SUBHASITANONT P,CHOKCHAICHAMNANKIT D,CHIABLAEM K,et al.Apigenin inhibits growth and induces apoptosis in human cholangiocarcinoma cells[J].Oncol Lett,2017,14(4):4361-4371.
[9]QIN Y,ZHAO D,ZHOU H G,et al.Apigenin inhibits NF-κBand Snail signaling,EMT and metastasis in human hepatocellular carcinoma[J].Oncotarget,2016,7(27):41421-41431.
[10]MIN X U,WANG S,SONG Y U,et al.Apigenin suppresses colorectal cancer cell proliferation,migration and invasion via inhibition of the Wnt/β-catenin signaling pathway[J].Oncol Lett,2016,11(5):3075-3080.
[11]WANG L,KUANG L,HITRON J A,et al.Apigenin suppresses migration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4expression[J].Toxicol Appl Pharmacol,2013,272(1):108-116.
[12]LI R B,YANG J S.Inhibitory effect of apigenin against migration and invasion of human lung cancer A549 cells and the related mechanism[J].Acad J Second Military Med Univ(第二军医大学学报),2015,36(8):878-882.
[13]ZHANG J Z,MA D L,ZHANG S H,et al.Effects of apigenin on the invasion ability of ovarian cancer cells by regulating Wnt signaling pathway[J].Anti-Tumor Pharmacy(肿瘤药学),2017,7(3):284-289.
[14]AMADO N G,PREDES D,MORENO M M,et al.Flavonoids and Wnt/β-catenin signaling:Potential role in colorectal cancer therapies[J].Int J Molecul Sci,2014,15(7):12094-12106.
[15]VILCHEZ V,TURCIOS L,MARTI F,et al.Targeting Wnt/β-catenin pathway in hepatocellular carcinoma treatment[J].World J Gastroenterol,2016,22(2):823-832.
[16]MOHAMMED M K,SHAO C,WANG J,et al.Wnt/β-catenin signaling plays an ever-expanding role in stem cell self-renewal,tumorigenesis and cancer chemoresistance[J].Gene Dis,2016,3(1):11-40.
[17]LIAO Y,SHEN W,KONG G,et al.Apigenin induces the apoptosis and regulates MAPK signaling pathways in mouse macrophage ANA-1 cells[J].Plos One,2014,9(3):e92007.
[18]KIM A,LEE C S.Apigenin reduces the Toll-like receptor-4-dependent activation of NF-?B by suppressing the Akt,m TOR,JNK,and p38-MAPK[J].Naunyn Schmiedebergs Arch Pharmacol,2018,391(3):271-283.
[19]LOW H B,ZHANG Y.Regulatory roles of mapk phosphatases in cancer[J].Immune Network,2016,16(2):85-98.
[20]KIM E K,CHOI E J.Compromised MAPK signaling in human diseases:an update[J].Arch Toxicol,2015,89(6):867-882.
[21]LU X,LI Y,LI X,et al.Luteolin induces apoptosis in vitro through suppressing the MAPK and PI3K signaling pathways in gastric cancer[J].Oncol Lett,2017,14(2):1993-2000.
[22]SURESH S,IRVINE A E.The NOTCH signaling pathway in normal andmalignant blood cell production[J].J Cell Commun Signal,2015,9(1):5-13.
[23]KIM B,STEPHEN S L,HANBY A M,et al.Chemotherapy induces Notch1-dependent MRP1 up-regulation,inhibition of which sensitizes breast cancer cells to chemotherapy[J].BMCCancer,2015,15(1):1-12.
[24]SHI F T,YU M,ZLOTY D,et al.Notch signaling is significantly suppressed in basal cell carcinomas and activation induces basal cell carcinoma cell apoptosis[J].Mol Med Rep,2017,15(4):1441-1454.
[25]FAN H,PAIBOONRUNGRUAN C,ZHANG X,et al.Nrf2regulates cellular behaviors and Notch signaling in oral squamous cell carcinoma cells[J].Biochem Biophys Res Commun,2017,493(1):833-839.
[26]LIN C H,CHANG C Y,LEE K R,et al.Flavones inhibit breast cancer proliferation through the Akt/FOXO3a signaling pathway[J].Bmc Cancer,2015,15(1):1-12.
[27]ERDOGAN S,DOGANLAR O,DOGANLAR Z B,et al.The flavonoid apigenin reduces prostate cancer CD44(+)stem cell survival and migration through PI3K/Akt/NF-κB signaling[J].Life Sci,2016(162):77-86
[28]邢海军,崔海燕,赵建虎.芹菜素通过下调MDR-1/P-gp表达逆转结肠癌耐药细胞HCT-8/5FU多药耐药性的作用及机制[J].中国老年学,2014(13):3709-3712.
[29]ERDOGAN S,TURKEKUL K,SERTTAS R,et al.The natural flavonoid apigenin sensitizes human CD44+prostate cancer stem cells to cisplatin therapy[J].Biomed Pharmacotherapy,2017,88(2017):210-217.
[30]ZHAO Y X,LIU J F,JIANG M H,et al.Effect of apigenin on the multidrug resistant breast cancer cell line MCF-7/ADR[J].China Oncol(中国癌症杂志),2017,27(8):648-654.
[31]SUH K S,OH S,WOO J T,et al.Apigenin attenuates2-deoxy-D-ribose-induced oxidative cell damage in HIT-T15pancreaticβ-cells[J].Biol Pharm Bull,2012,35(1):121-126.
[32]SINGH J P,SELVENDIRAN K,BANU S M,et al.Protective role of Apigenin on the status of lipid peroxidation and antioxidant defense against hepatocarcinogenesis in Wistar albino rats[J].Phytomedicine,2004,11(4):309-314.
[33]HU J,LI Z,XU L T,et al.Protective effect of apigenin on ischemia/reperfusion injury of the isolated rat heart[J].Cardiovasc Toxicol,2015,15(3):241-249.
[34]LI Z F.Research progress in antitumor effect and its mechanism of apigenin[J].J Dis Monitor Control(疾病监测与控制),2013,7(10):616-618.
[35]HONG J,FRISTIOHADY A,NGUYEN C H,et al.Apigenin and luteolin attenuate the breaching of MDA-MB231 breast cancer spheroids through the lymph endothelial barrier in vitro[J].Front Pharmacol,2018(9):1-10.