中药补骨脂抗肿瘤活性成分及作用机制的研究进展
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摘要
中药补骨脂(Fructus psoraleae)为豆科植物补骨脂(Psoralea corylifolia L.)的干燥成熟种子,广泛用于许多传统中医药配方中。现代医学研究表明,补骨脂中含多种抗肿瘤活性成分,包括补骨脂素、补骨脂定、补骨脂二氢黄酮、补骨脂查尔酮和补骨脂酚等;对肺癌、肝癌、乳腺癌及前列腺癌等多种恶性肿瘤细胞具有较好的增殖抑制作用。本文简要介绍补骨脂中抗肿瘤活性成分,并对主要成分及其作用机制的研究进展进行综述,探讨其抗肿瘤研究存在的问题及其开发应用前景,以期为进一步研究中药补骨脂的抗肿瘤作用提供借鉴和参考。
引文
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[2]Seo E,Oh Y S,Kim D,et al.Protective role of Psoralea corylifolia L.seed extract against hepatic mitochondrial dysfunction induced by oxidative stress or aging[J].Evid Based Complement Alternat Med,2013,2013:678028.
[3]Khushboo P S,Jadhav V M,Kadam V J,et al.Psoralea corylifolia linn.---“Kushtanashini”[J].Pharmacogn Rev,2010,4(7):69-76.
[4]Chopra B,Dhingra A K,Dhar K L.Psoralea corylifolia L.(Buguchi)-folklore to modern evidence:review[J].Fitoterapia,2013,90:44-56.
[5]Zhang,X,Zhao W,Wang Y,et al.The chemical constituents and bioactivities of Psoralea corylifolia Linn.:a review[J].Am J Chin Med,2016,44(1):35-60.
[6]郭江宁,吴侯,翁新楚.补骨脂中活性成分的提取分离与抗癌实验研究[J].中药材,2003,26(3):185-187.
[7]Sun N J,Woo S H,Cassady J M,et al.DNA polymerase and topoisomerase II inhibitors from Psoralea corylifolia[J].J Nat Prod,1998,61(3):363-366.
[8]韩建勋,吴军正,李焰,等.8-甲氧基补骨脂素对粘液表皮样癌细胞的抑制作用[J].实用口腔医学杂志,1998,14(4):286-287.
[9]Yang Y M,Hyun J W,Sung M S,et al.The cytotoxicity of psoralidin from psoralea corylifolia[J].Planta Med,1996,62(4):353-354.
[10]Yang Y,Tang X,Hao F,et al.Bavachin induces apoptosis through mitochondrial regulated ER stress pathway in HepG2cells[J].Biol Pharm Bull,2018,41(2):198-207.
[11]聂丽娟,李红梅,郭星,等.补骨脂抗氧化及抗肿瘤活性成分的研究[J].蚌埠医学院学报,2015,40(11):1461-1464.
[12]王安红,卢国彦,周昆,等.补骨脂乙素诱导HepG2细胞凋亡及对Bcl-2家族表达的影响[J].中药药理与临床,2012,28(5):23-25.
[13]Szliszka E,Czuba Z P,Sedek L,et al.Enhanced TRAIL-mediated apoptosis in prostate cancer cells by the bioactive compounds neobavaisoflavone and psoralidin isolated from Psoralea corylifolia[J].Pharmacol Rep,2011,63(1):139-148.
[14]Limper C,Wang Y,Ruhl S,et al.Compounds isolated from Psoralea corylifolia seeds inhibit protein kinase activity and induce apoptotic cell death in mammalian cells[J].J Pharm Pharmacol,2013,65(9):1393-1408.
[15]Bapat K,Chintalwar G J,Pandey U,et al.Preparation and in vitro evaluation of radioiodinated bakuchiol as an anti tumor agent[J].Appl Radiat Isot,2005,62(3):389-393.
[16]Latha P G,Evans D A,Panikkar K R,et al.Immunomodulatory and antitumour properties of Psoralea corylifolia seeds[J].Fitoterapia,2000,71(3):223-231.
[17]Whelan L C,Ryan M F.Ethanolic extracts of euphorbia and other ethnobotanical species as inhibitors of human tumour cell growth[J].Phytomedicine,2003,10(1):53-58.
[18]Song P,Yang X Z,Yuan J Q.Cytotoxic constituents from Psoralea corylifolia[J].J Asian Nat Prod Res,2013,15(6):624-630.
[19]张荣河,何三光.槲皮素、补骨脂素、异补骨脂素对人乳腺癌细胞P糖蛋白及耐药性影响的研究[J].中国医科大学学报,2000,4(29):713-715.
[20]Wang Y,Hong C,Zhou C,et al.Screening antitumor compounds psoralen and isopsoralen from Psoralea corylifolia L.seeds[J].Evid Based Complement Alternat Med,2011,2011:363052.
[21]张德杰,黄世林,陈楠楠,等.补骨脂素加长波紫外线照射对白血病K562细胞的杀伤作用[J].中西医结合学报,2005,3(6):65-68.
[22]蔡宇,陈冰,张荣华,等.补骨脂素对HL60细胞凋亡及细胞内Ca2+浓度影响的探讨[J].中国肿瘤临床,2006,33(2):64-66.
[23]Jiang Z,Xiong J.Induction of apoptosis in human hepatocarcinoma SMMC-7721cells in vitro by psoralen from Psoralea corylifolia[J].Cell Biochem Biophys,2014,70(2):1075-1081.
[24]Jiang J,Wang X,Cheng K,et al.Psoralen reverses the P-glycoprotein-mediated multidrug resistance in human breast cancer MCF-7/ADR cells[J].Mol Med Rep,2016,13(6):4745-4750.
[25]Suman S,Das T P,Damodaran C.Silencing NOTCHsignaling causes growth arrest in both breast cancer stem cells and breast cancer cells[J].Br J Cancer,2013,109(10):2587-2596.
[26]Ren G,Luo W,Sun W,et al.Psoralidin induced reactive oxygen species(ROS)-dependent DNA damage and protective autophagy mediated by NOX4in breast cancer cells[J].Phytomedicine,2016,23(9):939-947.
[27]Kumar R,Srinivasan S,Pahari P,et al.Activating stress-activated protein kinase-mediated cell death and inhibiting epidermal growth factor receptor signaling:a promising therapeutic strategy for prostate cancer[J].Mol Cancer Ther,2010,9(9):2488-2496.
[28]Das T P,Suman S,Damodaran C.Induction of reactive oxygen species generation inhibits epithelial-mesenchymal transition and promotes growth arrest in prostate cancer cells[J].Mol Carcinog,2014,53(7):537-547.
[29]Bronikowska J,Szliszka E,Jaworska D,et al,The coumarin psoralidin enhances anticancer effect of tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)[J].Molecules,2012,17(6):6449-6464.
[30]Hao W,Zhang X,Zhao W,et al.Psoralidin induces autophagy through ROS generation which inhibits the proliferation of human lung cancer A549cells[J].Peer J,2014,2:e555.
[31]Chen Z,Jin K,Gao L,et al.Anti-tumor effects of bakuchiol,an analogue of resveratrol,on human lung adenocarcinoma A549cell line[J].Eur J Pharmacol,2010,643(2-3):170-179.
[32]Kim J E,Kim J H,Lee Y,et al.Bakuchiol suppresses proliferation of skin cancer cells by directly targeting Hck,Blk,and p38MAP kinase[J].Oncotarget,2016,7(12):14616-14627.
[33]Li L,Chen X,Liu C C,et al.Phytoestrogen bakuchiol exhibits in vitro and in vivo anti-breast cancer effects by inducing S phase arrest and apoptosis[J].Front Pharmacol,2016,7:128.
[34]Li L,Liu C C,Chen X,et al.Mechanistic study of bakuchiol-induced anti-breast cancer stem cell and in vivo anti-metastasis effects[J].Front Pharmacol,2017,8:746.
[35]Lin J,Yao H J,Li R Y.Bakuchiol inhibits cell proliferation and induces apoptosis and cell cycle arrest in SGC-7901human gastric cancer cells[J].J Buon,2016,21(4):889-894.
[36]Lv L,Liu B.Anti-tumor effects of bakuchiol on human gastric carcinoma cell lines are mediated through PI3K/AKT and MAPK signaling pathways[J].Mol Med Rep,2017,16(6):8977-8982.
[37]Kim Y J,Choi W I,Ko H,et al.Neobavaisoflavone sensitizes apoptosis via the inhibition of metastasis in TRAIL-resistant human glioma U373MG cells[J].Life Sci,2014,95(2):101-107.
[38]Takeda T,Tsubaki M,Tomonari Y,et al.Bavachin induces the apoptosis of multiple myeloma cell lines by inhibiting the activation of nuclear factor kappa B and signal transducer and activator of transcription 3[J].Biomed Pharmacother,2018,100:486-494.
[39]Chen C Y,Chen C C,Shieh T M,et al.Corylin suppresses hepatocellular carcinoma progression via the inhibition of epithelial-mesenchymal transition,mediated by long noncoding RNA GAS5[J].Int J Mol Sci,2018,19(2):380.
[40]Chen C C,Chen C Y,Ueng S H,et al.Corylin increase the sensitivity of hepatocellular carcinoma cells to chemotherapy through long noncoding RNA RAD51-AS1-mediated inhibition of DNA repair[J].Cell Death Dis,2018,9(5):543.
[41]Wu C Z,Liu D C,Guo X,et al.Synthesis and evaluation of bakuchiol derivatives as potential anticancer agents[J].Molecules,2018,23(3):515.
[2]Seo E,Oh Y S,Kim D,et al.Protective role of Psoralea corylifolia L.seed extract against hepatic mitochondrial dysfunction induced by oxidative stress or aging[J].Evid Based Complement Alternat Med,2013,2013:678028.
[3]Khushboo P S,Jadhav V M,Kadam V J,et al.Psoralea corylifolia linn.---“Kushtanashini”[J].Pharmacogn Rev,2010,4(7):69-76.
[4]Chopra B,Dhingra A K,Dhar K L.Psoralea corylifolia L.(Buguchi)-folklore to modern evidence:review[J].Fitoterapia,2013,90:44-56.
[5]Zhang,X,Zhao W,Wang Y,et al.The chemical constituents and bioactivities of Psoralea corylifolia Linn.:a review[J].Am J Chin Med,2016,44(1):35-60.
[6]郭江宁,吴侯,翁新楚.补骨脂中活性成分的提取分离与抗癌实验研究[J].中药材,2003,26(3):185-187.
[7]Sun N J,Woo S H,Cassady J M,et al.DNA polymerase and topoisomerase II inhibitors from Psoralea corylifolia[J].J Nat Prod,1998,61(3):363-366.
[8]韩建勋,吴军正,李焰,等.8-甲氧基补骨脂素对粘液表皮样癌细胞的抑制作用[J].实用口腔医学杂志,1998,14(4):286-287.
[9]Yang Y M,Hyun J W,Sung M S,et al.The cytotoxicity of psoralidin from psoralea corylifolia[J].Planta Med,1996,62(4):353-354.
[10]Yang Y,Tang X,Hao F,et al.Bavachin induces apoptosis through mitochondrial regulated ER stress pathway in HepG2cells[J].Biol Pharm Bull,2018,41(2):198-207.
[11]聂丽娟,李红梅,郭星,等.补骨脂抗氧化及抗肿瘤活性成分的研究[J].蚌埠医学院学报,2015,40(11):1461-1464.
[12]王安红,卢国彦,周昆,等.补骨脂乙素诱导HepG2细胞凋亡及对Bcl-2家族表达的影响[J].中药药理与临床,2012,28(5):23-25.
[13]Szliszka E,Czuba Z P,Sedek L,et al.Enhanced TRAIL-mediated apoptosis in prostate cancer cells by the bioactive compounds neobavaisoflavone and psoralidin isolated from Psoralea corylifolia[J].Pharmacol Rep,2011,63(1):139-148.
[14]Limper C,Wang Y,Ruhl S,et al.Compounds isolated from Psoralea corylifolia seeds inhibit protein kinase activity and induce apoptotic cell death in mammalian cells[J].J Pharm Pharmacol,2013,65(9):1393-1408.
[15]Bapat K,Chintalwar G J,Pandey U,et al.Preparation and in vitro evaluation of radioiodinated bakuchiol as an anti tumor agent[J].Appl Radiat Isot,2005,62(3):389-393.
[16]Latha P G,Evans D A,Panikkar K R,et al.Immunomodulatory and antitumour properties of Psoralea corylifolia seeds[J].Fitoterapia,2000,71(3):223-231.
[17]Whelan L C,Ryan M F.Ethanolic extracts of euphorbia and other ethnobotanical species as inhibitors of human tumour cell growth[J].Phytomedicine,2003,10(1):53-58.
[18]Song P,Yang X Z,Yuan J Q.Cytotoxic constituents from Psoralea corylifolia[J].J Asian Nat Prod Res,2013,15(6):624-630.
[19]张荣河,何三光.槲皮素、补骨脂素、异补骨脂素对人乳腺癌细胞P糖蛋白及耐药性影响的研究[J].中国医科大学学报,2000,4(29):713-715.
[20]Wang Y,Hong C,Zhou C,et al.Screening antitumor compounds psoralen and isopsoralen from Psoralea corylifolia L.seeds[J].Evid Based Complement Alternat Med,2011,2011:363052.
[21]张德杰,黄世林,陈楠楠,等.补骨脂素加长波紫外线照射对白血病K562细胞的杀伤作用[J].中西医结合学报,2005,3(6):65-68.
[22]蔡宇,陈冰,张荣华,等.补骨脂素对HL60细胞凋亡及细胞内Ca2+浓度影响的探讨[J].中国肿瘤临床,2006,33(2):64-66.
[23]Jiang Z,Xiong J.Induction of apoptosis in human hepatocarcinoma SMMC-7721cells in vitro by psoralen from Psoralea corylifolia[J].Cell Biochem Biophys,2014,70(2):1075-1081.
[24]Jiang J,Wang X,Cheng K,et al.Psoralen reverses the P-glycoprotein-mediated multidrug resistance in human breast cancer MCF-7/ADR cells[J].Mol Med Rep,2016,13(6):4745-4750.
[25]Suman S,Das T P,Damodaran C.Silencing NOTCHsignaling causes growth arrest in both breast cancer stem cells and breast cancer cells[J].Br J Cancer,2013,109(10):2587-2596.
[26]Ren G,Luo W,Sun W,et al.Psoralidin induced reactive oxygen species(ROS)-dependent DNA damage and protective autophagy mediated by NOX4in breast cancer cells[J].Phytomedicine,2016,23(9):939-947.
[27]Kumar R,Srinivasan S,Pahari P,et al.Activating stress-activated protein kinase-mediated cell death and inhibiting epidermal growth factor receptor signaling:a promising therapeutic strategy for prostate cancer[J].Mol Cancer Ther,2010,9(9):2488-2496.
[28]Das T P,Suman S,Damodaran C.Induction of reactive oxygen species generation inhibits epithelial-mesenchymal transition and promotes growth arrest in prostate cancer cells[J].Mol Carcinog,2014,53(7):537-547.
[29]Bronikowska J,Szliszka E,Jaworska D,et al,The coumarin psoralidin enhances anticancer effect of tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)[J].Molecules,2012,17(6):6449-6464.
[30]Hao W,Zhang X,Zhao W,et al.Psoralidin induces autophagy through ROS generation which inhibits the proliferation of human lung cancer A549cells[J].Peer J,2014,2:e555.
[31]Chen Z,Jin K,Gao L,et al.Anti-tumor effects of bakuchiol,an analogue of resveratrol,on human lung adenocarcinoma A549cell line[J].Eur J Pharmacol,2010,643(2-3):170-179.
[32]Kim J E,Kim J H,Lee Y,et al.Bakuchiol suppresses proliferation of skin cancer cells by directly targeting Hck,Blk,and p38MAP kinase[J].Oncotarget,2016,7(12):14616-14627.
[33]Li L,Chen X,Liu C C,et al.Phytoestrogen bakuchiol exhibits in vitro and in vivo anti-breast cancer effects by inducing S phase arrest and apoptosis[J].Front Pharmacol,2016,7:128.
[34]Li L,Liu C C,Chen X,et al.Mechanistic study of bakuchiol-induced anti-breast cancer stem cell and in vivo anti-metastasis effects[J].Front Pharmacol,2017,8:746.
[35]Lin J,Yao H J,Li R Y.Bakuchiol inhibits cell proliferation and induces apoptosis and cell cycle arrest in SGC-7901human gastric cancer cells[J].J Buon,2016,21(4):889-894.
[36]Lv L,Liu B.Anti-tumor effects of bakuchiol on human gastric carcinoma cell lines are mediated through PI3K/AKT and MAPK signaling pathways[J].Mol Med Rep,2017,16(6):8977-8982.
[37]Kim Y J,Choi W I,Ko H,et al.Neobavaisoflavone sensitizes apoptosis via the inhibition of metastasis in TRAIL-resistant human glioma U373MG cells[J].Life Sci,2014,95(2):101-107.
[38]Takeda T,Tsubaki M,Tomonari Y,et al.Bavachin induces the apoptosis of multiple myeloma cell lines by inhibiting the activation of nuclear factor kappa B and signal transducer and activator of transcription 3[J].Biomed Pharmacother,2018,100:486-494.
[39]Chen C Y,Chen C C,Shieh T M,et al.Corylin suppresses hepatocellular carcinoma progression via the inhibition of epithelial-mesenchymal transition,mediated by long noncoding RNA GAS5[J].Int J Mol Sci,2018,19(2):380.
[40]Chen C C,Chen C Y,Ueng S H,et al.Corylin increase the sensitivity of hepatocellular carcinoma cells to chemotherapy through long noncoding RNA RAD51-AS1-mediated inhibition of DNA repair[J].Cell Death Dis,2018,9(5):543.
[41]Wu C Z,Liu D C,Guo X,et al.Synthesis and evaluation of bakuchiol derivatives as potential anticancer agents[J].Molecules,2018,23(3):515.