药学学报, 2019, 54(11): 1949-1957
张晓平, 邵骏菁, 马大龙, 刘帆, 刘苗苗, 崔清华. 天然药物抗肿瘤活性成分及其作用机制研究进展[J]. 药学学报, 2019, 54(11): 1949-1957.
ZHANG Xiao-ping, SHAO Jun-jing, MA Da-long, LIU Fan, LIU Miao-miao, CUI Qing-hua. Research on antitumor active components and mechanisms of natural products[J]. Acta Pharmaceutica Sinica, 2019, 54(11): 1949-1957.

张晓平1,2,3, 邵骏菁1,2, 马大龙4, 刘帆1,2, 刘苗苗1,2, 崔清华1,2
1. 山东中医药大学药学院, 山东 济南 250355;
2. 山东中医药大学青岛中医药科学院, 山东 青岛 266000;
3. 山东中医药大学中药学博士后流动站,山东 济南 250355;
4. 青岛大学附属医院药品调剂科, 山东 青岛 266005
关键词:    天然产物      抗肿瘤      活性成分      作用机制     
Research on antitumor active components and mechanisms of natural products
ZHANG Xiao-ping1,2,3, SHAO Jun-jing1,2, MA Da-long4, LIU Fan1,2, LIU Miao-miao1,2, CUI Qing-hua1,2
1. College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China;
2. Qingdao Academy of Chinese Medical Sciences, Shandong University of Traditional Chinese Medicine, Qingdao 266000, China;
3. TCM Post-doctoral Research Center, Shandong University of Traditional Chinese Medicine, Jinan 250355, China;
4. Department of Pharmacy, the Affiliated Hospital of Qingdao University, Qingdao 266005, China
Tumor, especially malignant tumor has become one of the major diseases, a serious threat to the health of people around the world. Modern clinical practice shows that the natural active products extracted from traditional Chinese medicine, marine medicine and other natural drugs, such as terpenes, alkaloids, polysaccharides, volatile oils and peptides, can effectively inhibit the growth of tumor cells. In this paper, the active components of natural antitumor products in recent years were summarized and their related mechanism was elucidated, so as to provide theoretical basis for the further development of natural antitumor drugs.
Key words:    natural product    antitumor    active component    mechanism   
收稿日期: 2019-08-22
DOI: 10.16438/j.0513-4870.2019-0669
基金项目: 山东省医药卫生科技发展计划项目(2016WS0579);国家重大新药创制专项(2017ZX09301030005);2019年山东省自然科学基金(ZR2019MH078);山东省高等学校科技计划项目(J18KA301).
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张晓平  在本刊中的所有文章
邵骏菁  在本刊中的所有文章
马大龙  在本刊中的所有文章
刘帆  在本刊中的所有文章
刘苗苗  在本刊中的所有文章
崔清华  在本刊中的所有文章

[1] Cao MM, Chen WQ. Epidemiology of cancer in China and the current status of prevention and control[J]. Chin J Clin Oncol (中国肿瘤临床), 2019, 46: 145-149.
[2] Sznarkowska A, Kostecka A, Meller K, et al. Inhibition of cancer antioxidant defense by natural compounds[J]. Oncotarget, 2017, 8: 15996-16016.
[3] Li JX, Li YR, Luo J, et al. Highlights of natural products research from China in 2018[J]. Acta Pharm Sin (药学学报), 2019, 54: 1333-1347.
[4] Shah BB, Baksi R, Chaudagar KK, et al. Anti-leukemic and anti-angiogenic effects of d-Limonene on K562-implanted C57BL/6 mice and the chick chorioallantoic membrane model[J]. Null, 2018, 1: 328-333.
[5] Huang QJ, Sun ZG, Long Y, et al. Research progress on the anticancer mechanism of d-limonene[J]. Food Sci (食品科学), 2015, 36: 240-244.
[6] Jiang Y, Liu X. Research progress in development and utilization of limonene[J]. China Food Safety Mag (食品安全导刊), 2018, (09): 133.
[7] Li YQ, Sun ZX. Study progress of norcantharidin based structural modification and drug combination for cancer[J]. Chin J Pharmacov (中国药物警戒), 2019, 16: 179-184.
[8] Zhang XM, Zhang BF, Zhang P, et al. Norcantharidin regulates ERα signaling and tamoxifen resistance via targeting miR-873/CDK3 in breast cancer cells[J]. PLoS One, 2019, 14: e0217181.
[9] Pan W, Zhang G. Linalool monoterpene exerts potent antitumor effects in OECM 1 human oral cancer cells by inducing sub-G1 cell cycle arrest, loss of mitochondrial membrane potential and inhibition of PI3K/AKT biochemical pathway[J]. J BUON, 2019, 24: 323-328.
[10] Guo LM, Lv JL, Zhang LB, et al. Research progress on anti-inflammatory mechanism of natural sesquiterpenoids[J]. China J Chin Mat Med (中国中药杂志), 2018, 43: 3989-3999.
[11] Ambrož M, Šmatová M, Šadibolová M, et al. Sesquiterpenes α-humulene and β-caryophyllene oxide enhance the efficacy of 5-fluorouracil and oxaliplatin in colon cancer cells[J]. Acta Pharm, 2019, 69: 121-128.
[12] Zhang L, Zhang J, Wang Y, et al. Efficacy of elemene injection assisted cisplatin in patients with non-small cell lung cancer and influence on the expression of mismatched repair proteins[J]. J Hebei Med (河北医学), 2019, 25: 70-75.
[13] Niu GY, Zhang X. Observation on efficacy of elemene injection combined with three-dimensional conformal intensity-modulated radiotherapy in treatment of advanced esophageal cancer[J]. Eva Anal Drug Use Hosp China (中国医院用药评价与分析), 2019, 19: 168-169, 172.
[14] Zhang Y, Sun X, Nan N, et al. Elemene inhibits the migration and invasion of 4T1 murine breast cancer cells via heparanase[J]. Mol Med Rep, 2017, 16: 794-800.
[15] Long J, Liu Z. Anti-tumor effect and mechanistic study of elemene on pancreatic carcinoma[J]. BMC Complement Altern Med, 2019, 19: 133.
[16] Liu YF, Zhou YM. The development of the application of paclitaxel and gemcitabine co-delivery drug system and their anti-tumor mechanism study[J]. Chin J New Drugs (中国新药杂志), 2019, 28: 1081-1086.
[17] Zheng L, Hu J, Xu Q, et al. Comparison of the efficacy of paclitaxel, paclitaxel liposome and albumin bound paclitaxel in head and neck tumors[J]. Chin J Mod Appl Pharm (中国现代应用药学), 2019, 36: 1391-1394.
[18] Chen FL, Lou YN, Kong XQ, et al. Research progress on antitumor effect and mechanisms of three terpenoids[J]. Guiding J Tradit Chin Med Pharmacol (中医药导报), 2018, 24: 45-49.
[19] Fang SD, Xiang RQ, Fan YD, et al. Advances in anti-tumor activities of pentacyclic triterpenoids[J]. Yunnan J Tradit Chin Med Mat Med (云南中医中药杂志), 2019, 40: 83-87.
[20] Liu P, Wang GQ. Advances on pharmacological action of pentacyclic triterpenoids[J]. Strait Pharm J (海峡药学), 2018, 30: 1-6.
[21] Liu L, Li M, Yu M, et al. Natural polysaccharides exhibit anti-tumor activity by targeting gut microbiota[J]. Int J Biol Macromol, 2019, 6: 743-751.
[22] Meng X, Liang H, Luo L. Antitumor polysaccharides from mushrooms: a review on the structural characteristics, antitumor mechanisms and immunomodulating activities[J]. Carbohydr Res, 2016, 424: 30-41.
[23] Wang JH, Zuo SR, Luo JP. Structural analysis and immuno-stimulating activity of an acidic polysaccharide from the stems of Dendrobium nobile Lindl[J]. Molecules, 2017, 22: 611.
[24] Zhang M, Zhang YR, Zhang LJ, et al. Mushroom polysaccharide lentinan for treating different types of cancers: a review of 12 years clinical studies in China[J]. Prog Mol Biol Transl Sci, 2019, 163: 297-328.
[25] Kim EJ, Park SY, Lee JY, et al. Fucoidan present in brown algae induces apoptosis of human colon cancer cells[J]. BMC Gastroenterol, 2010, 10: 96.
[26] Liu HC, Cai LH, Wang SY, et al. Progress on antitumor mechanisms of polyporus polysaccharide[J]. J Henan Univ Sci Technol (Med Sci)[河南科技大学学报(医学版)], 2011, 29: 236-238.
[27] Han J, Tang JC, Zhang F, et al. Research progress in anti-tumor mechanism of alkaloids[J]. Cent South Pharm (中南药学), 2018, 16: 987-990.
[28] Mathijssen RH, Loos WJ, Verweij J, et al. Pharmacology of topoisomerase I inhibitors irinotecan (CPT-11) and topotecan[J]. Curr Cancer Drug Targets, 2002, 2: 103-123.
[29] Zhao XY, Zhao R, Tian FY, et al. Effect of camptothecin (CPT) on the proliferation and apoptosis of PC-3 cells[J]. J Toxicol (毒理学杂志), 2018, 32: 264-267.
[30] Liu GQ, Shi S. Comparison of the effect of sequential cyclophosphamide and vincristine combined with cyclophosphamide on gastrointestinal malignant lymphoma[J]. Pract J Cancer (实用癌症杂志), 2018, 33: 1217-1218.
[31] Mao LM, Du XJ, Zhai QH, et al. Clinical study on matrine combined with carboplatin chemotherapy regimen in the treatment of middle and advanced cervical cancer[J]. China Pharm (中国药业), 2019, 28: 62-64.
[32] Farzaneh F, Shahghassempour S, Noshine B, et al. Application of tumor markers SCC-Ag, CEA and TPA in patients with cervical precancerous lesions[J]. Asian Pac J Cancer Prev, 2014, 15: 3911-3914.
[33] Min L, Zhong LX, Chen LN, et al. Clinical value of serum tumor markers SCC and TSGF in cervix carcinoma diagnose[J]. J Pract Med (实用医学杂志), 2014, 30: 898-900.
[34] He EM, Shen RC, Lin ZK, et al. A review on anti-tumor effects of soy isoflavones[J]. Subtrop Plant Sci (亚热带植物科学), 2013, 42: 356-360.
[35] Meng DS, Wang SL. Antitumor effect of quercetin[J]. Chin Tradit Herb Drugs (中草药), 2001, 32: 186-188.
[36] Zheng SY, Li Y, Jiang D, et al. Anticancer effect and apoptosis induction by quercetin in the human lung cancer cell line A-549[J]. Mol Med Rep, 2012, 5: 822-826.
[37] Noori-Daloii MR, Momeny M, Yousefi M, et al. Multifaceted preventive effects of single agent quercetin on a human prostate adeno-carcinoma cell line (PC-3): implications for nutritional transcriptomics and multi-target therapy[J]. Med Oncol, 2011, 28: 1395-1404.
[38] Wong MY, Chiu GN. Simultaneous liposomal delivery of quercetin and vincristine for enhanced estrogen receptor negative breast cancer treatment[J]. Anti Cancer Drugs, 2010, 21: 401-410.
[39] Yu M, Zhang YX. Research status of anti-tumor mechanism of resveratrol[J]. J Jilin Inst Chem Technol (吉林化工学院学报), 2019, 36: 12-15.
[40] Puissant A, Robert G, Fenouille N, et al. Resveratrol promotes autophagic cell death in chronic myelogenous leukemia cells via JNK-mediated p62/SQSTM1 expression and AMPK activation[J]. Cancer Res, 2010, 70: 1042-1052.
[41] Nakagawa H, Kiyozuka Y, Uemura Y, et al. Resveratrol inhibits human breast cancer cell growth and may mitigate the effect of linoleic acid, a potent breast cancer cell stimulator[J]. J Cancer Res Clin Oncol, 2001, 127: 258-264.
[42] Mouchiroud L, Molin L, Dallière N. Life span extension by resveratrol, rapamycin, and metformin: the promise of dietary restriction mimetics for an healthy aging[J]. Biofactors, 2010, 36: 377-382.
[43] Bishayee A, Politis T. Resveratrol in the chemoprevention and treatment of hepatocellular carcinoma[J]. Cancer Treat Rev, 2010, 36: 43-53.
[44] Atten MJ, Godoy-Romero E, Attar BM, et al. Resveratrol regulates cellular PKC alpha and delta to inhibit growth and induce apoptosis in gastric cancer cells[J]. Invest New Drugs, 2005, 23: 111-119.
[45] Chen XY, Gao F, Qian YC. Application mechanism of curcumin in tumor therapy[J]. Chin J Clin Ration Drug Use (临床合理用药杂志), 2019, 12: 175-176.
[46] Zhou YF, Ye YQ, Fan PH. Research progress on structural modification and antitumor activity of betulinol and betulinic acid[J]. J Shenyang Pharm Univ (沈阳药科大学学报), 2017, 34: 838-847.
[47] Pan HS, Li L, Cui HB, et al. Synthesis and anti-tumor activity of derivatives of ursolic acid in vitro[J]. Acta Pharm Sin (药学学报), 2017, 52: 1890-1894.
[48] Yuan XF, Tian WC, Xie JM, et al. Rhein enhances the cytotoxicity of effector lymphocyte to colon cancer in hypoxia[J]. Chin J Surg Integr Tradit West Med (中国中西医结合外科杂志), 2018, 24: 476-481.
[49] Kumar Singh V, Das S, Kumar Dwivedy A, et al. Assessment of chemically characterized Salvia sclarea L essential oil and its combination with linalyl acetate as novel plant based antifungal, antiaflatoxigenic and antioxidant agent against herbal drugs contamination and probable mode of action[J]. Nat Prod Res, 2019, 2: 1-6.
[50] Yang C, Tang J, Xiong SH, et al. Anti-tumor activity of volatile oil in Chinese medicine[J]. Cent South Pharm (中南药学), 2017, 15: 1190-1194.
[51] Zhang XQ, Shao LX, Wu WC, et al. On the anti-bacterial and anti-tumor functions of Atractylodes macrocephala Koidz volatile oil[J]. J Zhejiang Norm Univ (Nat Sci)[浙江师范大学学报(自然科学版)], 2016, 39: 436-442.
[52] Zhang ZS, Zhang YX, Chen SY, et al. Effects of volatile oil from DangGui on cell cycle and proliferation of human lung adenocarcinoma GLC-82 cells[J]. West J Tradit Chin Med (西部中医药), 2018, 31: 8-12.
[53] Jiang JL, Ding HT, Su X. Study on identification of anti-tumor active components of turmeric volatile oil based on group-effect relationship[J]. Chin J Anal Chem (分析化学), 2012, 40: 1488-1493.
[54] Tu YH, Kang YQ, Zhou Y, et al. Effect of turmeric volatile oil on the proliferation and apoptosis of human leukemia cell line THP-1[J]. J Shandong Univ (Health Sci)[山东大学学报(医学版)], 2015, 53: 46.
[55] Han SN, Li Y, Zhang XH, et al. Extraction and antitumor activity of essential oil from Zanthoxylum bungeanum seeds[J]. Food Sci (食品科学), 2014, 35: 13-16.
[56] Hakkim FL, Bakshi HA, Khan S, et al. Frankincense essential oil suppresses melanoma cancer through down regulation of Bcl-2/Bax cascade signaling and ameliorates heptotoxicity via phase I and II drug metabolizing enzymes[J]. Oncotarget, 2019, 10: 3472-3490.
[57] Dong J, Liang W, Wang T, et al. Saponins regulate intestinal inflammation in colon cancer and IBD[J]. Pharmacol Res, 2019, 144: 66-72.
[58] Peng WT, Sun WY, Sun JC, et al. Effects of ginsenoside CK on the migration and invasion of human hepatocellular carcinoma cells HepG2[J]. Chin Pharmacol Bull (中国药理学通报), 2018, 34: 27-32.
[59] Hu SS, Yan KM, Wang JJ, et al. Effect of ginsenoside Rh2 on drug resistance sensitivity of human gastric cancer SGC7901/ADR cells[J]. Chin Tradit Herb Drugs (中草药), 2018, 49: 4113-4117.
[60] Wang YJ, Hu HY, Wang T, et al. Growth inhibition of ginsenoside Rg3 on gastric (SNU-216) cells[J]. Ginseng Res (人参研究), 2019, 31: 18-19.
[61] Zhang DD, Shang DJ. Potential of antimicrobial peptides as novel anti-infective therapeutics and application prospect[J]. Chin J Biochem Pharm, 2016, 36: 178-182.
[62] Chen ZF, Bai L. Research progress in the source and mechanism of the anti-tumor polypeptidedrugs[J]. Immunol J (免疫学杂志), 2018, 34: 1099-1104.
[63] Ou HL, Chang X, Wang C, et al. Preliminary study of peptide from Periplaneta americana on antitumor immunity in L1210-bearing mice[J]. Chin Pharm J (中国药学杂志), 2018, 53: 353-358.
[64] Ding J, Chua PJ, Bay BH, et al. Scorpion venoms as a potential source of novel cancer therapeutic compounds[J]. Exp Biol Med (Maywood), 2014, 239: 387-393.
[65] Tao GZ, Ye BP. Preliminary study on marine source fungi and their cytotoxic activities[J]. Sci Technol Innov (科学技术创新), 2019, (18): 32-33.
[66] Shi QW, Li LG, Huo CH, et al. Research outline of marine natural products[J]. Chin Tradit Herb Drugs (中草药), 2010, 41: 1031-1047.
[67] Zhang JY, Fu LW. Advance of several types of important marine anti-tumor drug[J]. Acta Pharm Sin (药学学报), 2008, 43: 435-442.
[68] Wang Q, Liang H, Liu Y, et al. Effect of aplysin on invasion and immunomodulatory of hepatocarcinoma 22 in mice[J]. Chin J Public Health (中国公共卫生), 2014, 30: 1265-1267.
[69] Guo J, Dong W, Liu W, et al. Synthesis and cytotoxicity of 3-aryl acrylic amide derivatives of the simplified saframycin-ecteinascidin skeleton prepared from L-dopa[J]. Eur J Med Chem, 2013, 62: 670-676.
[70] Amin ARMR, Karpowicz PA, Carey TE, et al. Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds[J]. Semin Cancer Biol, 2015, 35 Suppl: S55-S77.
[71] Baek SJ, Okazaki R, Lee SH, et al. Nonsteroidal anti-inflammatory drug-activated gene-1 over expression in transgenic mice suppresses intestinal neoplasia[J]. Gastroenterology, 2006, 131: 1553-1560.
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