苦杏仁苷抗肿瘤机制的研究进展
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摘要
近年来肿瘤的发病率越来越高,虽然采取了综合疗法,但晚期恶性肿瘤死亡率仍处于较高水平。随着中草药研究的深入,研究人员发现多种中草药具有良好的抗肿瘤作用。苦杏仁苷主要存在于苦杏仁中,除了具有抗氧化、抗菌、抗炎、免疫调节等作用外,还具有抗肿瘤的特性。本文总结了苦杏仁苷的结构特征、抗肿瘤机制及研究进展,为探索其抗肿瘤的临床应用奠定了理论基础。苦杏仁苷可通过影响细胞周期、诱导细胞凋亡、细胞毒作用、调节机体免疫功能等在肺癌、膀胱癌、肾细胞癌等实体肿瘤中发挥抗肿瘤作用。进一步深入研究苦杏仁苷的药理机制,在发挥其抗肿瘤作用的同时减少毒副作用,尽快实现苦杏仁苷的临床应用。
In recent years, the incidence of cancer is getting higher and higher, although the comprehensive treatment is used, but the mortality rate of advanced malignant tumors is still at a high level. With the further research of Traditional Chinese Medicine(TCM), we find that a variety of TCM has a good anti-tumor effect.Amygdalin is contained mainly in bitter almonds, in addition to anti-oxidation, antibacterial, anti-inflammatory,immune regulation, amygdalin also has anti-tumor effect. This article summarized the structural characteristics anti-tumor mechanisms and research progress of amygdalin, to explore its anti-tumor clinical value and theoretical foundation. Amygdalin has anti-tumor effects in solid tumors such as lung cancer, bladder cancer and renal cell carcinoma by affecting cell cycle, inducing apoptosis, cytotoxicity and regulating immune function. To achieve an earlier clinical application, we need further study the pharmacological mechanism of amygdalin, to explore its antitumor effect while reducing its side effects.
In recent years, the incidence of cancer is getting higher and higher, although the comprehensive treatment is used, but the mortality rate of advanced malignant tumors is still at a high level. With the further research of Traditional Chinese Medicine(TCM), we find that a variety of TCM has a good anti-tumor effect.Amygdalin is contained mainly in bitter almonds, in addition to anti-oxidation, antibacterial, anti-inflammatory,immune regulation, amygdalin also has anti-tumor effect. This article summarized the structural characteristics anti-tumor mechanisms and research progress of amygdalin, to explore its anti-tumor clinical value and theoretical foundation. Amygdalin has anti-tumor effects in solid tumors such as lung cancer, bladder cancer and renal cell carcinoma by affecting cell cycle, inducing apoptosis, cytotoxicity and regulating immune function. To achieve an earlier clinical application, we need further study the pharmacological mechanism of amygdalin, to explore its antitumor effect while reducing its side effects.
引文
[1]Chen W,Zheng R,Baade PD,et al.Cancer statistics in China,2015.CA Cancer J Clin,2016,66(2):115-132
[2]杨秀美,胡小勤.广西常用中草药抗肿瘤机制研究进展.辽宁中医药大学学报,2012,14(05):60-62
[3]Orlikova B,Legrand N,Panning J,et al.Anti-inflammatory and anticancer drugs from nature.Cancer Treat Res,2014,159:123-143
[4]Lea MA,Koch MR.Effects of cyanate,thiocyanate,and amygdalin on metabolite uptake in normal and neoplastic tissues of the rat.J Natl Cancer Inst,1979,63(5):1279-1283
[5]邢国秀,李楠,杨姜燕.天然苦杏仁苷的研究进展.中成药,2003,25(12):1007-1009
[6]Jiagang D,Li C,Wang H,Hao E,et al.Amygdalin mediates relieved atherosclerosis in apolipoprotein E deficient mice through the induction of regulatory T cells.Biochem Biophs Res Commun,2011,411(3):523-529
[7]李露,戴婷,李小龙,等.苦杏仁苷药理作用的研究进展.吉林医药学院学报,2016,37(1):63-66
[8]Makarevic J,Tsaur I,Juengel E,et al.Amygdalin delays cell cycle progression and blocks growth of prostate cancer cells in vitro.Life Sci,2016,147:137-142
[9]Park HJ,Yoon SH,Han LS,et al.Amygdalin inhibits genes related to cell cycle in SNU-C4 human colon cancer cells.World J Gastroenterol,2005,11(33):5156-5161
[10]Chen Y,Ma J,Wang F,et al.Amygdalin induces apoptosis in human cervical cancer cell line HeLa cells.Immunopharmacol Immunotoxicol,2013,35(1):43-51
[11]Chang HK,Shin MS,Yang HY,et al.Amygdalin induces apoptosis through regulation of Bax and Bcl-2 expressions in human DU145 and LNCaP prostate cancer cells.Biol Pharm Bull,2006,29(8):1597-1602
[12]许宁侠.苦杏仁苷的研究进展.内蒙古中医药,2012,31(9):66-67
[13]吕建珍,邓家刚.苦杏仁苷的药理作用研究进展.现代药物与临床,2012,27(5):530-535
[14]Li YL,Li QX,Liu RJ,Shen XQ.Chinese medicine amygdalin andβ-glucosidase combined with antibody enzymatic prodrug system as a feasible antitumor therapy.Chin J Integr Med,2018,24(3):237-240
[15]张冲,刘丽春,郭利君.HMFG1-β-葡萄糖苷酶偶联物联合苦杏仁苷体外对膀胱癌EJ细胞杀伤作用的研究.卫生职业教育,2016,34(12):146-147
[16]Moertel CG,Ames MM,Kovach JS,et al.A pharmacologic and toxicological study of amygdalin.JAMA,1981,245(6):591-594
[17]Roman AB,Karen N,Axel H,et al.Amygdalin,quackery or cure.Phymedicine,2016,23(4):367-376
[18]Liczbiński P,Bukowska B.Molecular mechanism of amygdalin action in vitro:review of the latest research.Immunopharmacol Immunotoxicol,2018,40(3):212-218
[19]Baroni A,Paoletti I,Greco R,et al.Immunomodulatory effects of a set of amygdalin analogues on human keratinocyte cells.Exp Dermatol,2005,14(11):854-859
[20]Jiagang D,Li C,Wang H,et al.Amygdalin mediates relieved atherosclerosis in apolipoprotein E deficient mice through the induction of regulatory T cells.Biochem Biophys Res Commun,2011,411(3):523-529
[21]Lv J,Xiong W,Lei T,et al.Amygdalin ameliorates the progression of atherosclerosis in LDL receptor-deficient mice.Mol Med Rep,2017,16(6):8171-8179
[22]Qian L,Xie B,Wang Y,et al.Amygdalin-mediated inhibition of nonsmall cell lung cancer cell invasion in vitro.Int J Clin Pathol,2015,8(5):5363-5370
[23]Makarevic J,Rutz J,Juengel E,et al.Amygdalin influences bladder cancer cell adhesion and invasion in vitro.PLoS One,2014,9(10):e110244
[24]Makarevic J,Rutz J,Juengel E,et al.Amygdalin blocks bladder cancer cell growth in vitro by diminishing cyclin A and cdk2.PLoS One,2014,9(8):e105590
[25]Syrigos KN,Rowlinson-Busza G,Epenetos AA.In vitro cytotoxicity following specific activation of amygdalin by beta-glucosidase conjugated to a bladder cancerassociated monoclonal antibody.Int J Cancer,1998,78(6):712-719
[26]Juengel E,Thomas A,Rutz J,et al.Amygdalin inhibits the growth of renal cell carcinoma cells in vitro.Int JMol Med,2016,37(2):526-532
[27]Juengel E,Afschar M,Makarevic J,et al.Amygdalin blocks the in vitro adhesion and invasion of renal cell carcinoma cells by an integrin-dependent mechanism.Int J Mol Med,2016,37(3):843-850
[28]Lee HM,Moon A.Amygdalin regulates apoptosis and adhesion in Hs578T triple-negative breast cancer cells.Biomol Ther(Seoul),2016,24(1):62-66
[29]Kwon HY,Hong SP,Hahn DH,Kim JH.Apoptosis induction of Persicae Semen extract in human promyelocytic leukemia(HL-60)cells.Arch Pharm Res,2003,26(2):157-161
[30]孙卓琳,刘京伟,匡长春.苦杏仁苷抑制人肺癌NCI-H1299细胞体外侵袭的机制.中国药科大学学报,2016,47(4):479-482
[31]Do JS,Hwang JK,Seo HJ,Woo WH,Nam SY.Antiasthmatic activity and selective inhibition of type 2 helper Tcell response by aqueous extract of semen armeniacae amarum.Immunopharmacol Immunotoxicol,2006,28(2):213-225
[32]常立文,祝华平,李文斌.苦杏仁甙对高氧暴露早产鼠肺泡II型细胞的保护作用.中华儿科杂志,2005,43(2):118-123
[33]刑国秀,李楠,杨美燕等.天然苦杏仁苷的研究进展.中成药,2003,25(12):1007-1009
[34]Shim SM,Kwon H.Metabolites of amygdalin under simulated human digestive fluids.Int J Food Sci Nutr,2010,61(8):770-779
[35]Tafti LD,Shariatpanahi SM,Damghani MM,et al.Traditional Persian topical medications for gastrointestinal diseases.Iran J Basic Med Sci,2017,20(3):222-241
[36]Lv J,Xiong W,Lei T,et al.Amygdalin ameliorates the progression of atherosclerosis in LDL receptor-deficient mice.Mol Med Rep,2017,16(6):8171-8179
[2]杨秀美,胡小勤.广西常用中草药抗肿瘤机制研究进展.辽宁中医药大学学报,2012,14(05):60-62
[3]Orlikova B,Legrand N,Panning J,et al.Anti-inflammatory and anticancer drugs from nature.Cancer Treat Res,2014,159:123-143
[4]Lea MA,Koch MR.Effects of cyanate,thiocyanate,and amygdalin on metabolite uptake in normal and neoplastic tissues of the rat.J Natl Cancer Inst,1979,63(5):1279-1283
[5]邢国秀,李楠,杨姜燕.天然苦杏仁苷的研究进展.中成药,2003,25(12):1007-1009
[6]Jiagang D,Li C,Wang H,Hao E,et al.Amygdalin mediates relieved atherosclerosis in apolipoprotein E deficient mice through the induction of regulatory T cells.Biochem Biophs Res Commun,2011,411(3):523-529
[7]李露,戴婷,李小龙,等.苦杏仁苷药理作用的研究进展.吉林医药学院学报,2016,37(1):63-66
[8]Makarevic J,Tsaur I,Juengel E,et al.Amygdalin delays cell cycle progression and blocks growth of prostate cancer cells in vitro.Life Sci,2016,147:137-142
[9]Park HJ,Yoon SH,Han LS,et al.Amygdalin inhibits genes related to cell cycle in SNU-C4 human colon cancer cells.World J Gastroenterol,2005,11(33):5156-5161
[10]Chen Y,Ma J,Wang F,et al.Amygdalin induces apoptosis in human cervical cancer cell line HeLa cells.Immunopharmacol Immunotoxicol,2013,35(1):43-51
[11]Chang HK,Shin MS,Yang HY,et al.Amygdalin induces apoptosis through regulation of Bax and Bcl-2 expressions in human DU145 and LNCaP prostate cancer cells.Biol Pharm Bull,2006,29(8):1597-1602
[12]许宁侠.苦杏仁苷的研究进展.内蒙古中医药,2012,31(9):66-67
[13]吕建珍,邓家刚.苦杏仁苷的药理作用研究进展.现代药物与临床,2012,27(5):530-535
[14]Li YL,Li QX,Liu RJ,Shen XQ.Chinese medicine amygdalin andβ-glucosidase combined with antibody enzymatic prodrug system as a feasible antitumor therapy.Chin J Integr Med,2018,24(3):237-240
[15]张冲,刘丽春,郭利君.HMFG1-β-葡萄糖苷酶偶联物联合苦杏仁苷体外对膀胱癌EJ细胞杀伤作用的研究.卫生职业教育,2016,34(12):146-147
[16]Moertel CG,Ames MM,Kovach JS,et al.A pharmacologic and toxicological study of amygdalin.JAMA,1981,245(6):591-594
[17]Roman AB,Karen N,Axel H,et al.Amygdalin,quackery or cure.Phymedicine,2016,23(4):367-376
[18]Liczbiński P,Bukowska B.Molecular mechanism of amygdalin action in vitro:review of the latest research.Immunopharmacol Immunotoxicol,2018,40(3):212-218
[19]Baroni A,Paoletti I,Greco R,et al.Immunomodulatory effects of a set of amygdalin analogues on human keratinocyte cells.Exp Dermatol,2005,14(11):854-859
[20]Jiagang D,Li C,Wang H,et al.Amygdalin mediates relieved atherosclerosis in apolipoprotein E deficient mice through the induction of regulatory T cells.Biochem Biophys Res Commun,2011,411(3):523-529
[21]Lv J,Xiong W,Lei T,et al.Amygdalin ameliorates the progression of atherosclerosis in LDL receptor-deficient mice.Mol Med Rep,2017,16(6):8171-8179
[22]Qian L,Xie B,Wang Y,et al.Amygdalin-mediated inhibition of nonsmall cell lung cancer cell invasion in vitro.Int J Clin Pathol,2015,8(5):5363-5370
[23]Makarevic J,Rutz J,Juengel E,et al.Amygdalin influences bladder cancer cell adhesion and invasion in vitro.PLoS One,2014,9(10):e110244
[24]Makarevic J,Rutz J,Juengel E,et al.Amygdalin blocks bladder cancer cell growth in vitro by diminishing cyclin A and cdk2.PLoS One,2014,9(8):e105590
[25]Syrigos KN,Rowlinson-Busza G,Epenetos AA.In vitro cytotoxicity following specific activation of amygdalin by beta-glucosidase conjugated to a bladder cancerassociated monoclonal antibody.Int J Cancer,1998,78(6):712-719
[26]Juengel E,Thomas A,Rutz J,et al.Amygdalin inhibits the growth of renal cell carcinoma cells in vitro.Int JMol Med,2016,37(2):526-532
[27]Juengel E,Afschar M,Makarevic J,et al.Amygdalin blocks the in vitro adhesion and invasion of renal cell carcinoma cells by an integrin-dependent mechanism.Int J Mol Med,2016,37(3):843-850
[28]Lee HM,Moon A.Amygdalin regulates apoptosis and adhesion in Hs578T triple-negative breast cancer cells.Biomol Ther(Seoul),2016,24(1):62-66
[29]Kwon HY,Hong SP,Hahn DH,Kim JH.Apoptosis induction of Persicae Semen extract in human promyelocytic leukemia(HL-60)cells.Arch Pharm Res,2003,26(2):157-161
[30]孙卓琳,刘京伟,匡长春.苦杏仁苷抑制人肺癌NCI-H1299细胞体外侵袭的机制.中国药科大学学报,2016,47(4):479-482
[31]Do JS,Hwang JK,Seo HJ,Woo WH,Nam SY.Antiasthmatic activity and selective inhibition of type 2 helper Tcell response by aqueous extract of semen armeniacae amarum.Immunopharmacol Immunotoxicol,2006,28(2):213-225
[32]常立文,祝华平,李文斌.苦杏仁甙对高氧暴露早产鼠肺泡II型细胞的保护作用.中华儿科杂志,2005,43(2):118-123
[33]刑国秀,李楠,杨美燕等.天然苦杏仁苷的研究进展.中成药,2003,25(12):1007-1009
[34]Shim SM,Kwon H.Metabolites of amygdalin under simulated human digestive fluids.Int J Food Sci Nutr,2010,61(8):770-779
[35]Tafti LD,Shariatpanahi SM,Damghani MM,et al.Traditional Persian topical medications for gastrointestinal diseases.Iran J Basic Med Sci,2017,20(3):222-241
[36]Lv J,Xiong W,Lei T,et al.Amygdalin ameliorates the progression of atherosclerosis in LDL receptor-deficient mice.Mol Med Rep,2017,16(6):8171-8179