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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Review Article

癌症治疗和转移化学预防中的熊果酸：从合成衍生物到临床前研究中的纳米制剂

卷 19, 期 4, 2019

页: [245 - 256] 页: 12

弟呕挨: 10.2174/1568009618666181016145940

价格: $65

摘要

背景：癌症转移已成为导致大多数癌症死亡的主要公共卫生威胁。传统的化学治疗剂在过去是有效的，但是治疗效率低且有害的副作用。最近，据报道，熊果酸（UA）是天然丰富的五环三萜之一，具有广泛的生物活性，包括抗炎，抗动脉粥样硬化和抗癌特性。更重要的是，UA具有低毒，肝脏保护和抗癌转移潜力的特点。目的：本文旨在回顾UA在癌症治疗领域用作抑制肿瘤起始，进展和转移的候选药物的巨大潜力。 方法：使用数据库开始至2017年12月的关键字和副标题，在Pubmed，Google Scholar和Web of Science中进行选择性搜索。此处总结了系统评价。 结果：UA主要通过诱导细胞凋亡，抑制细胞增殖，预防肿瘤血管生成和转移，发挥癌症的化学预防和治疗作用。 UA纳米制剂可以增强UA的溶解度和生物利用度，并且对肿瘤生长和转移具有更好的抑制作用。 结论：本文提供的信息可为进一步研究UA作为一种有前途的抗癌药物，特别是作为临床应用的预防性转移药物提供有用的参考。

关键词: 熊果酸，癌症转移，化学预防，机制，UA衍生物，UA纳米制剂。

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[1]
Ferlay, J.; Shin, H.R.; Bray, F.; Forman, D.; Mathers, C.; Parkin, D.M. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J. Cancer, 2010, 127(12), 2893-2917.
[2]
DeSantis, C.E.; Lin, C.C.; Mariotto, A.B.; Siegel, R.L.; Stein, K.D.; Kramer, J.L.; Alteri, R.; Robbins, A.S.; Jemal, A. Cancer treatment and survivorship statistics, 2014. CA Cancer J. Clin., 2014, 64(4), 252-271.
[3]
Shanmugam, M.K.; Nguyen, A.H.; Kumar, A.P.; Tan, B.K.H.; Sethi, G. Targeted inhibition of tumor proliferation, survival, and metastasis by pentacyclic triterpenoids: Potential role in prevention and therapy of cancer. Cancer Lett., 2012, 320(2), 158-170.
[4]
Zhang, J.; Li, Y.; Chen, S.S.; Zhang, L.; Wang, J.; Yang, Y.; Zhang, S.; Pan, Y.; Wang, Y.; Yang, L. Systems pharmacology dissection of the anti-inflammatory mechanism for the medicinal herb Folium eriobotryae. Int. J. Mol. Sci., 2015, 16(2), 2913-2941.
[5]
Chen, H.; Yang, J.; Zhang, Q.; Chen, L.H.; Wang, Q. Corosolic acid ameliorates atherosclerosis in apolipoprotein E-deficient mice by regulating the nuclear factor-kappaB signaling pathway and inhibiting monocyte chemoattractant protein-1 expression. Circ. J., 2012, 76(4), 995-1003.
[6]
Wei, J.; Liu, M.; Liu, H.; Wang, H.; Wang, F.; Zhang, Y.; Han, L.; Lin, X. Oleanolic acid arrests cell cycle and induces apoptosis via ROS-mediated mitochondrial depolarization and lysosomal membrane permeabilization in human pancreatic cancer cells. J. Appl. Toxicol., 2013, 33(8), 756-765.
[7]
(a) Juan, M.E.; Planas, J.M.; Ruiz-Gutierrez, V.; Daniel, H.; Wenzel, U. Antiproliferative and apoptosis-inducing effects of maslinic and oleanolic acids, two pentacyclic triterpenes from olives, on HT-29 colon cancer cells. Br. J. Nutr., 2008, 100(1), 36-43.
(b) Li, J.; Guo, W.J.; Yang, Q.Y. Effects of ursolic acid and oleanolic acid on human colon carcinoma cell line HCT15. World J. Gastroenterol., 2002, 8(3), 493-495.
[8]
Li, J.; Guo, W.J.; Yang, Q.Y. Effects of ursolic acid and oleanolic acid on human colon carcinoma cell line HCT15. World J. Gastroenterol., 2002, 8(3), 493-495.
[9]
(a) Bishayee, A.; Ahmed, S.; Brankov, N.; Perloff, M. Triterpenoids as potential agents for the chemoprevention and therapy of breast cancer. Front. Biosci., 2011, 16, 980-996.
(b) Allouche, Y.; Warleta, F.; Campos, M.; Sanchez-Quesada, C.; Uceda, M.; Beltran, G.; Gaforio, J.J. Antioxidant, antiproliferative, and pro-apoptotic capacities of pentacyclic triterpenes found in the skin of olives on MCF-7 human breast cancer cells and their effects on DNA damage. J. Agric. Food Chem., 2011, 59(1), 121-130.
[10]
Allouche, Y.; Warleta, F.; Campos, M.; Sanchez-Quesada, C.; Uceda, M.; Beltran, G.; Gaforio, J.J. Antioxidant, antiproliferative, and pro-apoptotic capacities of pentacyclic triterpenes found in the skin of olives on MCF-7 human breast cancer cells and their effects on DNA damage. J. Agric. Food Chem., 2011, 59(1), 121-130.
[11]
He, X.J.; Liu, R.H. Triterpenoids isolated from apple peels have potent antiproliferative activity and may be partially responsible for apple’s anticancer activity. J. Agric. Food Chem., 2007, 55(11), 4366-4370.
[12]
Kassi, E.; Papoutsi, Z.; Pratsinis, H.; Aligiannis, N.; Manoussakis, M.; Moutsatsou, P. Ursolic acid, a naturally occurring triterpenoid, demonstrates anticancer activity on human prostate cancer cells. J. Cancer Res. Clin., 2007, 133(7), 493-500.
[13]
Harikumar, K.B.; Sung, B.; Pandey, M.K.; Guha, S.; Krishnan, S.; Aggarwal, B.B. Escin, a pentacyclic triterpene, chemosensitizes human tumor cells through inhibition of nuclear factor-kappa B signaling pathway. Mol. Pharmacol., 2010, 77(5), 818-827.
[14]
(a) Janicsák, G.; Veres, K.; Zoltán Kakasy, A.; Máthé, I. Study of the oleanolic and ursolic acid contents of some species of the Lamiaceae. Biochem. Syst. Ecol., 2006, 34(5), 392-396.
(b) Silva, M.G.; Vieira, I.G.; Mendes, F.N.; Albuquerque, I.L.; dos Santos, R.N.; Silva, F.O.; Morais, S.M. Variation of ursolic acid content in eight Ocimum species from northeastern Brazil. Molecules, 2008, 13(10), 2482-2487.
[15]
Silva, M.G.V.; Vieira, I.G.P.; Mendes, F.N.P.; Albuquerque, I.L.; dos Santos, R.N.; Silva, F.O.; Morais, S.M. Variation of ursolic acid content in eight Ocimum species from northeastern Brazil. Molecules, 2008, 13(10), 2482-2487.
[16]
Ngo, S.N.T.; Williams, D.B.; Head, R.J. Rosemary and cancer prevention: Preclinical perspectives. Crit. Rev. Food Sci. , 2011, 51(10), 946-954.
[17]
Wang, Z.H.; Hsu, C.C.; Huang, C.N.; Yin, M.C. Anti-glycative effects of oleanolic acid and ursolic acid in kidney of diabetic mice. Eur. J. Pharmacol., 2010, 628(1-3), 255-260.
[18]
Ohigashi, H.; Takamura, H.; Koshimizu, K.; Tokuda, H.; Ito, Y. Search for possible antitumor promoters by inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus activation; ursolic acid and oleanolic acid from an anti-inflammatory Chinese medicinal plant, Glechoma hederaceae L. Cancer Lett., 1986, 30(2), 143-151.
[19]
Andersson, D.; Liu, J.J.; Nilsson, A.; Duan, R.D. Ursolic acid inhibits proliferation and stimulates apoptosis in HT29 cells following activation of alkaline sphingomyelinase. Anticancer Res., 2003, 23(4), 3317-3322.
[20]
(a) Wang, J.; Liu, L.; Qiu, H.; Zhang, X.; Guo, W.; Chen, W.; Tian, Y.; Fu, L.; Shi, D.; Cheng, J.; Huang, W.; Deng, W. Ursolic acid simultaneously targets multiple signaling pathways to suppress proliferation and induce apoptosis in colon cancer cells. PLoS One, 2013, 8(5), e63872.
(b) Shan, J.Z.; Xuan, Y.Y.; Zhang, Q.; Huang, J.J. Ursolic acid sensitized colon cancer cells to chemotherapy under hypoxia by inhibiting MDR1 through HIF-1 alpha. J. Zhejiang Univ. Sci. B, 2016, 17(9), 672-682.
[21]
Shan, J.Z.; Xuan, Y.Y.; Zhang, Q.; Huang, J.J. Ursolic acid sensitized colon cancer cells to chemotherapy under hypoxia by inhibiting MDR1 through HIF-1 alpha. J. Zhejiang Univ. Sci. B, 2016, 17(9), 672-682.
[22]
(a) Jin, H.; Pi, J.; Yang, F.; Jiang, J.; Wang, X.; Bai, H.; Shao, M.; Huang, L.; Zhu, H.; Yang, P.; Li, L.; Li, T.; Cai, J.; Chen, Z.W. Folate-chitosan nanoparticles loaded with ursolic acid confer anti-breast cancer activities in vitro and in vivo. Sci. Rep., 2016, 6, 30782.
(b) Yeh, C.T.; Wu, C.H.; Yen, G.C. Ursolic acid, a naturally occurring triterpenoid, suppresses migration and invasion of human breast cancer cells by modulating c-Jun N-terminal kinase, Akt and mammalian target of rapamycin signaling. Mol. Nutr. Food Res., 2010, 54(9), 1285-1295.
[23]
Yeh, C.T. Ursolic acid, a naturally occurring triterpenoid, suppresses migration and invasion of human breast cancer cells by modulating c-Jun N-terminal kinase, Akt and mammalian target of rapamycin signaling. Mol. Nutr. Food Res., 2010, 54(11), 1696-1696.
[24]
(a) Zhang, H.; Zheng, D.H.; Ding, J.; Xu, H.E.; Li, X.L.; Sun, W.H. Efficient delivery of ursolic acid by poly(N-vinylpyrrolidone)-block-poly (epsilon-caprolactone) nanoparticles for inhibiting the growth of hepatocellular carcinoma in vitro and in vivo. Int. J. Nanomedicine, 2015, 10, 1909-1920.
(b) Gayathri, R.; Priya, D.K.; Gunassekaran, G.R.; Sakthisekaran, D. Ursolic acid attenuates oxidative stress-mediated hepatocellular carcinoma induction by diethylnitrosamine in male Wistar rats. Asian Pac. J. Cancer Prev., 2009, 10(5), 933-938.
[25]
Gayathri, R.; Priya, D.K.D.; Gunassekaran, G.R.; Sakthisekaran, D. Ursolic acid attenuates oxidative stress-mediated hepatocellular carcinoma induction by diethylnitrosamine in male wistar rats. Asian Pac. J. Cancer Prev., 2009, 10(5), 933-938.
[26]
Shanmugam, M.K.; Ong, T.H.; Kumar, A.P.; Lun, C.K.; Ho, P.C.; Wong, P.T.; Hui, K.M.; Sethi, G. Ursolic acid inhibits the initiation, progression of prostate cancer and prolongs the survival of TRAMP mice by modulating pro-inflammatory pathways. PLoS One, 2012, 7(3), e32476.
[27]
Gao, N.; Cheng, S.P.; Budhraja, A.; Gao, Z.Y.; Chen, J.P.; Liu, E.H.; Huang, C.; Chen, D.Y.; Yang, Z.L.; Liu, Q.; Li, P.; Shi, X.L.; Zhang, Z. Ursolic acid induces apoptosis in human leukaemia cells and exhibits anti-leukaemic activity in nude mice through the PKB pathway. Br. J. Pharmacol., 2012, 165(6), 1813-1826.
[28]
Du, H.; Chen, X.Q. CD-MEKC method to analyze triterpene acids in traditional chinese medicines. J. Braz. Chem. Soc., 2009, 20(7), 1268-1274.
[29]
Liu, H. Oleanolic acid and ursolic acid: Research perspectives. J. Ethnopharmacol., 2005, 100(1-2), 92-94.
[30]
Maulvi, F.A.; Dalwadi, S.J.; Thakkar, V.T.; Soni, T.G.; Gohel, M.C.; Gandhi, T.R. Improvement of dissolution rate of aceclofenac by solid dispersion technique. Powder Technol., 2011, 207(1-3), 47-54.
[31]
Hsu, Y.L.; Kuo, P.L.; Lin, C.C. Proliferative inhibition, cell-cycle dysregulation, and induction of apoptosis by ursolic acid in human non-small cell lung cancer A549 cells. Life Sci., 2004, 75(19), 2303-2316.
[32]
van Horssen, R.; ten Hagen, T.L.M.; Eggermont, A.M.M. TNF-alpha in cancer treatment: Molecular insights, antitumor effects, and clinical utility. Oncologist, 2006, 11(4), 397-408.
[33]
Tamm, I.; Wang, Y.; Sausville, E.; Scudiero, D.A.; Vigna, N.; Oltersdorf, T.; Reed, J.C. IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res., 1998, 58(23), 5315-5320.
[34]
Curtin, N.J.; Szabo, C. Therapeutic applications of PARP inhibitors: anticancer therapy and beyond. Mol. Aspects Med., 2013, 34(6), 1217-1256.
[35]
(a) Zhang, Y.X.; Kong, C.Z.; Wang, L.H.; Li, J.Y.; Liu, X.K.; Xu, B.; Xu, C.L.; Sun, Y.H. Ursolic acid overcomes Bcl-2-mediated resistance to apoptosis in prostate cancer cells involving activation of JNK-induced Bcl-2 phosphorylation and degradation. J. Cell. Biochem., 2010, 109(4), 764-773.
(b) Park, J.H.; Kwon, H.Y.; Sohn, E.J.; Kim, K.A.; Kim, B.; Jeong, S.J.; Song, J.H.; Koo, J.S.; Kim, S.H. Inhibition of Wnt/beta-catenin signaling mediates ursolic acid-induced apoptosis in PC-3 prostate cancer cells. Pharmacol. Rep., 2013, 65(5), 1366-1374.
[36]
Park, J.H.; Kwon, H.Y.; Sohn, E.J.; Kim, K.A.; Kim, B.; Jeong, S.J.; Song, J.H.; Koo, J.S.; Kim, S.H. Inhibition of Wnt/beta-catenin signaling mediates ursolic acid-induced apoptosis in PC-3 prostate cancer cells. Pharmacol. Rep., 2013, 65(5), 1366-1374.
[37]
Hsu, Y.L.; Kuo, P.L.; Lin, C.C. Proliferative inhibition, cell-cycle dysregulation, and induction of apoptosis by ursolic acid in human non-small cell lung cancer A549 cells. Life Sci., 2004, 75(19), 2303-2316.
[38]
(a) Li, Y.; Xing, D.; Chen, Q.; Chen, W.R. Enhancement of chemotherapeutic agent-induced apoptosis by inhibition of NF-kappaB using ursolic acid. Int. J. Cancer, 2010, 127(2), 462-473.
(b) Manu, K.A.; Kuttan, G. Ursolic acid induces apoptosis by activating p53 and caspase-3 gene expressions and suppressing NF-kappaB mediated activation of bcl-2 in B16F-10 melanoma cells. Int. Immunopharmacol., 2008, 8(7), 974-981.
(c) Gao, X.; Deeb, D.; Jiang, H.; Liu, Y.; Dulchavsky, S.A.; Gautam, S.C. Synthetic triterpenoids inhibit growth and induce apoptosis in human glioblastoma and neuroblastoma cells through inhibition of prosurvival Akt, NF-kappaB and Notch1 signaling. J. Neurooncol., 2007, 84(2), 147-157.
[39]
Manu, K.A.; Kuttan, G. Ursolic acid induces apoptosis by activating p53 and caspase-3 gene expressions and suppressing NF-kappa B mediated activation of bcl-2 in B16F-10 melanoma cells. Int. Immunopharmacol., 2008, 8(7), 974-981.
[40]
Gao, X.; Deeb, D.; Jiang, H.; Liu, Y.; Dulchavsky, S.A.; Gautam, S.C. Synthetic triterpenoids inhibit growth and induce apoptosis in human glioblastoma and neuroblastoma cells through inhibition of prosurvival Akt, NF-kappa B and Notch1 signaling. J. Neurooncol., 2007, 84, 147-157.
[41]
Limami, Y.; Pinon, A.; Leger, D.Y.; Mousseau, Y.; Cook-Moreau, J.; Beneytout, J.L.; Delage, C.; Liagre, B.; Simon, A. HT-29 colorectal cancer cells undergoing apoptosis overexpress COX-2 to delay ursolic acid-induced cell death. Biochimie, 2011, 93(4), 749-757.
[42]
Achiwa, Y.; Hasegawa, K.; Udagawa, Y. Regulation of the phosphatidylinositol 3-kinase-Akt and the mitogen-activated protein kinase pathways by ursolic acid in human endometrial cancer cells. Biosci. Biotechnol. Biochem., 2007, 71(1), 31-37.
[43]
Pathak, A.K.; Bhutani, M.; Nair, A.S.; Ahn, K.S.; Chakraborty, A.; Kadara, H.; Guha, S.; Sethi, G.; Aggarwal, B.B. Ursolic acid inhibits STAT3 activation pathway leading to suppression of proliferation and chemosensitization of human multiple myeloma cells. Mol. Cancer Res., 2007, 5(9), 943-955.
[44]
Prasad, S.; Yadav, V.R.; Kannappan, R.; Aggarwal, B.B. Ursolic acid, a pentacyclin triterpene, potentiates TRAIL-induced apoptosis through p53-independent up-regulation of death receptors (Retraction of vol 286, pg 5546, 2011). J. Biol. Chem., 2016, 291(32), 16924-16924.
[45]
Lauthier, F.; Taillet, L.; Trouillas, P.; Delage, C.; Simon, A. Ursolic acid triggers calcium-dependent apoptosis in human Daudi cells. Anticancer Drugs, 2000, 11(9), 737-745.
[46]
Tu, H.Y.; Huang, A.M.; Wei, B.L.; Gan, K.H.; Hour, T.C.; Yang, S.C.; Pu, Y.S.; Lin, C.N. Ursolic acid derivatives induce cell cycle arrest and apoptosis in NTUB1 cells associated with reactive oxygen species. Bioorg. Med. Chem., 2009, 17(20), 7265-7274.
[47]
Liu, X.S.; Jiang, J.K. Induction of apoptosis and regulation of the MAPK pathway by ursolic acid in human leukemia K562 cells. Planta Med., 2007, 73(11), 1192-1194.
[48]
Zhang, Y.X.; Kong, C.Z.; Wang, L.H.; Li, J.Y.; Liu, X.K.; Xu, B.; Xu, C.L.; Sun, Y.H. Ursolic acid overcomes Bcl-2-mediated resistance to apoptosis in prostate cancer cells involving activation of JNK-Induced Bcl-2 phosphorylation and degradation. J. Cell. Biochem., 2010, 109(4), 764-773.
[49]
Gao, N.; Cheng, S.P.; Budhraja, A.; Gao, Z.Y.; Chen, J.P.; Liu, E.H.; Huang, C.; Chen, D.Y.; Yang, Z.L.; Liu, Q.; Li, P.; Shi, X.L.; Zhang, Z. Ursolic acid induces apoptosis in human leukaemia cells and exhibits anti-leukaemic activity in nude mice through the PKB pathway. Br. J. Pharmacol., 2012, 165(6), 1813-1826.
[50]
Liu, X.S.; Jiang, J.K. Induction of apoptosis and regulation of the MAPK pathway by ursolic acid in human leukemia K562 cells. Planta Med., 2007, 73(11), 1192-1194.
[51]
Manu, K.A.; Kuttan, G. Ursolic acid induces apoptosis by activating p53 and caspase-3 gene expressions and suppressing NF-kappaB mediated activation of bcl-2 in B16F-10 melanoma cells. Int. Immunopharmacol., 2008, 8(7), 974-981.
[52]
Achiwa, Y.; Hasegawa, K.; Udagawa, Y. Regulation of the phosphatidylinositol 3-kinase-Akt and the mitogen-activated protein kinase pathways by ursolic acid in human endometrial cancer cells. Biosci. Biotechnol. Biochem., 2007, 71(1), 31-37.
[53]
Hanahan, D.; Weinberg, R.A. The hallmarks of cancer. Cell, 2000, 100(1), 57-70.
[54]
Kiran, M.S.; Viji, R.I.; Sameer Kumar, V.B.; Sudhakaran, P.R. Modulation of angiogenic factors by ursolic acid. Biochem. Biophys. Res. Commun., 2008, 371(3), 556-560.
[55]
Kanjoormana, M.; Kuttan, G. Antiangiogenic activity of ursolic acid. Integr. Cancer Ther., 2010, 9(2), 224-235.
[56]
Das, B.; Yeger, H.; Tsuchida, R.; Torkin, R.; Gee, M.F.W.; Thorner, P.S.; Shibuya, M.; Malkin, D.; Baruchel, S. A hypoxia-driven vascular endothelial growth factor/Flt1 autocrine loop interacts with hypoxia-inducible factor-1 alpha through mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 pathway in neuroblastoma. Cancer Res., 2005, 65(16), 7267-7275.
[57]
Gupta, G.P. Massague, J. Cancer metastasis: building a framework. Cell, 2006, 127(4), 679-695.
[58]
Wan, L.L.; Pantel, K.; Kang, Y.B. Tumor metastasis: moving new biological insights into the clinic. Nat. Med., 2013, 19(11), 1450-1464.
[59]
Hamano, Y.; Zeisberg, M.; Sugimoto, H.; Lively, J.C.; Maeshima, Y.; Yang, C.; Hynes, R.O.; Werb, Z.; Sudhakar, A.; Kalluri, R. Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin. Cancer Cell, 2003, 3(6), 589-601.
[60]
Pritchard, S.C.; Nicolson, M.C.; Lloret, C.; McKay, J.A.; Ross, V.G.; Kerr, K.M.; Murray, G.I.; McLeod, H.L. Expression of matrix metalloproteinases 1, 2, 9 and their tissue inhibitors in stage II non-small cell lung cancer: Implications for MMP inhibition therapy. Oncol. Rep., 2001, 8(2), 421-424.
[61]
Guo, C.B.; Wang, S.; Deng, C.; Zhang, D.L.; Wang, F.L.; Jin, X.Q. Relationship between matrix metalloproteinase 2 and lung cancer progression. Mol. Diagn. Ther., 2007, 11(3), 183-192.
[62]
Hung, W.C.; Tseng, W.L.; Shiea, J.; Chang, H.C. Skp2 overexpression increases the expression of MMP-2 and MMP-9 and invasion of lung cancer cells. Cancer Lett., 2010, 288(2), 156-161.
[63]
Insug, O.; Otvos, Jr L.; Kieber-Emmons, T.; Blaszczyk-Thurin, M. Role of SA-Le(a) and E-selectin in metastasis assessed with peptide antagonist. Peptides, 2002, 23(5), 999-1010.
[64]
Xiang, L.P.; Chi, T.; Tang, Q.; Yang, X.; Ou, M.R.; Chen, X.F.; Yu, X.B.; Chen, J.Z.; Ho, R.J.Y.; Shao, J.W.; Jia, L. A pentacyclic triterpene natural product, ursolic acid and its prodrug US597 inhibit targets within cell adhesion pathway and prevent cancer metastasis. Oncotarget, 2015, 6(11), 9295-9312.
[65]
Huang, C.Y.; Lin, C.Y.; Tsai, C.W.; Yin, M.C. Inhibition of cell proliferation, invasion and migration by ursolic acid in human lung cancer cell lines. Toxicol. In Vitro, 2011, 25(7), 1274-1280.
[66]
Shishodia, S.; Majumdar, S.; Banerjee, S.; Aggarwal, B.B. Ursolic acid inhibits nuclear factor-kappa B activation induced by carcinogenic agents through suppression of I kappa B alpha kinase and p65 phosphorylation: Correlation with down-regulation of cyclooxygenase 2, matrix metalloproteinase 9, and cyclin D1. Cancer Res., 2003, 63(15), 4375-4383.
[67]
Yim, E.K.; Lee, M.J.; Lee, K.H.; Um, S.J.; Park, J.S. Antiproliferative and antiviral mechanisms of ursolic acid and dexamethasone in cervical carcinoma cell lines. Int. J. Gynecol. Cancer, 2006, 16(6), 2023-2031.
[68]
Prasad, S.; Yadav, V.R.; Sung, B.; Gupta, S.C.; Tyagi, A.K.; Aggarwal, B.B. Ursolic acid inhibits the growth of human pancreatic cancer and enhances the antitumor potential of gemcitabine in an orthotopic mouse model through suppression of the inflammatory microenvironment. Oncotarget, 2016, 7(11), 13182-13196.
[69]
Caldeira de Araujo Lopes, S.; Vinicius Melo Novais, M.; Salviano Teixeira, C.; Honorato-Sampaio, K.; Tadeu Pereira, M.; Ferreira, L.A.; Braga, F.C.; Cristina Oliveira, M. Preparation, physicochemical characterization, and cell viability evaluation of long-circulating and pH-sensitive liposomes containing ursolic acid. BioMed Res. Int., 2013, 2013, 467147.
[70]
Meng, Y.Q.; Liu, D.; Cai, L.L.; Chen, H.; Cao, B.; Wang, Y.Z. The synthesis of ursolic acid derivatives with cytotoxic activity and the investigation of their preliminary mechanism of action. Bioorg. Med. Chem., 2009, 17(2), 848-854.
[71]
Chadalapaka, G.; Jutooru, I.; McAlees, A.; Stefanac, T.; Safe, S. Structure-dependent inhibition of bladder and pancreatic cancer cell growth by 2-substituted glycyrrhetinic and ursolic acid derivatives. Bioorg. Med. Chem. Lett., 2008, 18(8), 2633-2639.
[72]
(a) Chen, L.; Qiu, W.; Tang, J.; Wang, Z.F.; He, S.Y. Synthesis and bioactivity of novel nitric oxide-releasing ursolic acid derivatives. Chin. Chem. Lett., 2011, 22(4), 413-416.
(b) Meng, Y-Q.; Liu, D.; Cai, L-L.; Chen, H.; Cao, B.; Wang, Y-Z. The synthesis of ursolic acid derivatives with cytotoxic activity and the investigation of their preliminary mechanism of action. Bioorg. Med. Chem., 2009, 17(2), 848-854.
[73]
Ma, C.M.; Cai, S.Q.; Cui, J.R.; Wang, R.Q.; Tu, P.F.; Hattori, M.; Daneshtalab, M. The cytotoxic activity of ursolic acid derivatives. Eur. J. Med. Chem., 2005, 40(6), 582-589.
[74]
Tu, H-Y.; Huang, A.M.; Wei, B-L.; Gan, K-H.; Hour, T-C.; Yang, S-C.; Pu, Y-S.; Lin, C-N. Ursolic acid derivatives induce cell cycle arrest and apoptosis in NTUB1 cells associated with reactive oxygen species. Bioorg. Med. Chem., 2009, 17(20), 7265-7274.
[75]
Meng, Y.Q.; Cao, J.; Tang, Y.; Lu, X.Y.; Liu, L.W. Synthesis and anti-tumor activity of derivatives of ring a of ursolic acid. Chinese J. Org. Chem., 2016, 36(5), 1080-1087.
[76]
Liu, D.; Meng, Y.Q.; Zhao, J.; Chen, L.G. Synthesis and anti-tumor activity of novel amide derivatives of ursolic acid. Chem. Res. Chin. Univ., 2008, 24(1), 42-46.
[77]
Liu, M.C.; Yang, S.J.; Jin, L.H.; Hu, D.Y.; Xue, W.; Song, B.A.; Yang, S. Synthesis and cytotoxicity of novel ursolic acid derivatives containing an acyl piperazine moiety. Eur. J. Med. Chem., 2012, 58, 128-135.
[78]
Bai, K.K.; Yu, Z.; Chen, F.L.; Li, F.; Li, W.Y.; Guo, Y.H. Synthesis and evaluation of ursolic acid derivatives as potent cytotoxic agents. Bioorg. Med. Chem. Lett., 2012, 22(7), 2488-2493.
[79]
Wang, J.C.; Jiang, Z.; Xiang, L.P.; Li, Y.F.; Ou, M.R.; Yang, X.; Shao, J.W.; Lu, Y.S.; Lin, L.F.; Chen, J.Z.; Dai, Y.; Jia, L. Synergism of ursolic acid derivative US597 with 2-deoxy-D-glucose to preferentially induce tumor cell death by dual-targeting of apoptosis and glycolysis. Sci. Rep-UK, 2014, 4, 5006.
[80]
Dong, H.; Yang, X.; Xie, J.; Xiang, L.; Li, Y.; Ou, M.; Chi, T.; Liu, Z.; Yu, S.; Gao, Y.; Chen, J.; Shao, J.; Jia, L. UP12, a novel ursolic acid derivative with potential for targeting multiple signaling pathways in hepatocellular carcinoma. Biochem. Pharmacol., 2015, 93(2), 151-162.
[81]
Liu, D.; Meng, Y.Q.; Zhao, J.; Chen, L.G. Synthesis and anti-tumor activity of novel amide derivatives of ursolic acid. Chem. Res. Chin. Univ., 2008, 24(1), 42-46.
[82]
Shao, J.W.; Dai, Y.C.; Xue, J.P.; Wang, J.C.; Lin, F.P.; Guo, Y.H. In vitro and In vivo anticancer activity evaluation of ursolic acid derivatives. Eur. J. Med. Chem., 2011, 46(7), 2652-2661.
[83]
Mendes, V.I.; Bartholomeusz, G.A.; Ayres, M.; Gandhi, V.; Salvador, J.A. Synthesis and cytotoxic activity of novel A-ring cleaved ursolic acid derivatives in human non-small cell lung cancer cells. Eur. J. Med. Chem., 2016, 123, 317-331.
[84]
Fu, S.B.; Yang, J.S.; Cui, J.L.; Feng, X.; Sun, D.A. Biotransformation of ursolic acid by an endophytic fungus from medicinal plant Huperzia serrata. Chem. Pharm. Bull. , 2011, 59(9), 1180-1182.
[85]
Tang, Q.; Liu, Y.; Li, T.; Yang, X.; Zheng, G.; Chen, H.; Jia, L.; Shao, J. A novel co-drug of aspirin and ursolic acid interrupts adhesion, invasion and migration of cancer cells to vascular endothelium via regulating EMT and EGFR-mediated signaling pathways: multiple targets for cancer metastasis prevention and treatment. Oncotarget, 2016, 7(45), 73114-73129.
[86]
Yoon, Y.; Lim, J.W.; Kim, J.; Kim, Y.; Chun, K.H. Discovery of ursolic acid prodrug (NX-201): Pharmacokinetics and in vivo antitumor effects in PANC-1 pancreatic cancer. Bioorg. Med. Chem. Lett., 2016, 26(22), 5524-5527.
[87]
Jorgensen, W.L. The many roles of computation in drug discovery. Science, 2004, 303(5665), 1813-1818.
[88]
Clark, L.A.; Boriack-Sjodin, P.A.; Eldredge, J.; Fitch, C.; Friedman, B.; Hanf, K.J.M.; Jarpe, M.; Liparoto, S.F.; Li, Y.; Lugovskoy, A.; Miller, S.; Rushe, M.; Sherman, W.; Simon, K.; Van Vlijmen, H. Affinity enhancement of an in vivo matured therapeutic antibody using structure-based computational design. Protein Sci., 2006, 15(5), 949-960.
[89]
Cong, X.; Topin, J.; Golebiowski, J.; Class, A. GPCRs: Structure, function, modeling and structure-based ligand design. Curr. Pharm. Des., 2017, 23(29), 4390-4409.
[90]
Xiang, L.; Chi, T.; Tang, Q.; Yang, X.; Ou, M.; Chen, X.; Yu, X.; Chen, J.; Ho, R.J.; Shao, J.; Jia, L. A pentacyclic triterpene natural product, ursolic acid and its prodrug US597 inhibit targets within cell adhesion pathway and prevent cancer metastasis. Oncotarget, 2015, 6(11), 9295-9312.
[91]
(a) Baek, S.; Singh, R.K.; Khanal, D.; Patel, K.D.; Lee, E.J.; Leong, K.W.; Chrzanowski, W.; Kim, H.W. Smart multifunctional drug delivery towards anticancer therapy harmonized in mesoporous nanoparticles. Nanoscale, 2015, 7(34), 14191-14216.
(b) Chan, J.M.; Zhang, L.; Yuet, K.P.; Liao, G.; Rhee, J.W.; Langer, R.; Farokhzad, O.C. PLGA-lecithin-PEG core-shell nanoparticles for controlled drug delivery. Biomaterials, 2009, 30(8), 1627-1634.
[92]
Chan, J.M.; Zhang, L.F.; Yuet, K.P.; Liao, G.; Rhee, J.W.; Langer, R.; Farokhzad, O.C. PLGA-lecithin-PEG core-shell nanoparticles for controlled drug delivery. Biomaterials, 2009, 30(8), 1627-1634.
[93]
Kraft, J.C.; Freeling, J.P.; Wang, Z.; Ho, R.J. Emerging research and clinical development trends of liposome and lipid nanoparticle drug delivery systems. J. Pharm. Sci., 2014, 103(1), 29-52.
[94]
Wilson, B.; Samanta, M.K.; Santhi, K.; Kumar, K.P.; Ramasamy, M.; Suresh, B. Chitosan nanoparticles as a new delivery system for the anti-Alzheimer drug tacrine. Nanotechnol. Biol. Med., 2010, 6(1), 144-152.
[95]
(a) Zentner, G.M.; Rathi, R.; Shih, C.; McRea, J.C.; Seo, M.H.; Oh, H.; Rhee, B.G.; Mestecky, J.; Moldoveanu, Z.; Morgan, M.; Weitman, S. Biodegradable block copolymers for delivery of proteins and water-insoluble drugs. J. Control. Release, 2001, 72(1-3), 203-215.
(b) Chen, S.; Pieper, R.; Webster, D.C.; Singh, J. Triblock copolymers: synthesis, characterization, and delivery of a model protein. Int. J. Pharm., 2005, 288(2), 207-218.
[96]
Chen, S.B.; Pieper, R.; Webster, D.C.; Singh, J. Triblock copolymers: synthesis, characterization, and delivery of a model protein. Int. J. Pharm., 2005, 288(2), 207-218.
[97]
Chen, C.; Geng, J.; Pu, F.; Yang, X.; Ren, J.; Qu, X. Polyvalent nucleic acid/mesoporous silica nanoparticle conjugates: dual stimuli-responsive vehicles for intracellular drug delivery. Angew. Chem., 2011, 50(4), 882-886.
[98]
Zhang, X.; Li, N.; Liu, Y.; Ji, B.; Wang, Q.; Wang, M.; Dai, K.; Gao, D. On-demand drug release of ICG-liposomal wedelolactone combined photothermal therapy for tumor. Nanotechnol. Biol. Med., 2016, 12(7), 2019-2029.
[99]
Zhao, T.; Liu, Y.; Gao, Z.; Gao, D.; Li, N.; Bian, Y.; Dai, K.; Liu, Z. Self-assembly and cytotoxicity study of PEG-modified ursolic acid liposomes. Mater. Boil. Appl., 2015, 53, 196-203.
[100]
Yang, G.; Yang, T.; Zhang, W.; Lu, M.; Ma, X.; Xiang, G. In vitro and In vivo antitumor effects of folate-targeted ursolic acid stealth liposome. J. Agric. Food Chem., 2014, 62(10), 2207-2215.
[101]
Wang, M.L.; Zhao, T.T.; Liu, Y.P.; Wang, Q.Q.; Xing, S.S.; Li, L.; Wang, L.G.; Liu, L.X.; Gao, D.W. Ursolic acid liposomes with chitosan modification: Promising antitumor drug delivery and efficacy. Mat. Sci. Eng. C-Mater., 2017, 71, 1231-1240.
[102]
Rao, W.; Wang, H.; Han, J.F.; Zhao, S.T.; Dumbleton, J.; Agarwal, P.; Zhang, W.J.; Zhao, G.; Yu, J.H.; Zynger, D.L.; Lu, X.B.; He, X.M. Chitosan-decorated doxorubicin-encapsulated nanoparticle targets and eliminates tumor reinitiating cancer stem-like cells. ACS Nano, 2015, 9(6), 5725-5740.
[103]
Jin, H.; Pi, J.; Yang, F.; Wu, C.; Cheng, X.; Bai, H.; Huang, D.; Jiang, J.; Cai, J.; Chen, Z.W. Ursolic acid-loaded chitosan nanoparticles induce potent anti-angiogenesis in tumor. Appl. Microbiol. Biotechnol., 2016, 100(15), 6643-6652.
[104]
Bally, F.; Garg, D.K.; Serra, C.A.; Hoarau, Y.; Anton, N.; Brochon, C.; Parida, D.; Vandamme, T.; Hadziioannou, G. Improved size-tunable preparation of polymeric nanoparticles by microfluidic nanoprecipitation. Polymer , 2012, 53(22), 5045-5051.
[105]
Zhang, H.; Li, X.; Ding, J.; Xu, H.; Dai, X.; Hou, Z.; Zhang, K.; Sun, K.; Sun, W. Delivery of ursolic acid (UA) in polymeric nanoparticles effectively promotes the apoptosis of gastric cancer cells through enhanced inhibition of cyclooxygenase 2 (COX-2). Int. J. Pharm., 2013, 441(1-2), 261-268.
[106]
Ge, Z-Q.; Du, X-Y.; Huang, X-N.; Qiao, B. Enhanced oral bioavailability of ursolic acid nanoparticles via antisolvent precipitation with TPGS1000 as a stabilizer. J. Drug Deliv. Sci. Technol., 2015, 29, 210-217.
[107]
Baishya, R.; Nayak, D.K.; Kumar, D.; Sinha, S.; Gupta, A.; Ganguly, S.; Debnath, M.C. Ursolic acid loaded plga nanoparticles: In vitro and in vivo evaluation to explore tumor targeting ability on B16F10 melanoma cell lines. Pharm. Res., 2016, 33(11), 2691-2703.
[108]
Chen, X.; Chen, J.; Li, B.; Yang, X.; Zeng, R.; Liu, Y.; Li, T.; Ho, R.J.; Shao, J. PLGA-PEG-PLGA triblock copolymeric micelles as oral drug delivery system: In vitro drug release and in vivo pharmacokinetics assessment. J. Colloid Interface Sci., 2017, 490, 542-552.
[109]
Antonio, E.; Antunes, O.D.J.; de Araujo, I.S.; Khalil, N.M.; Mainardes, R.M. Poly(lactic acid) nanoparticles loaded with ursolic acid: Characterization and in vitro evaluation of radical scavenging activity and cytotoxicity. Mat. Sci. Eng. C Mater., 2017, 71, 156-166.
[110]
Kaminskas, L.M.; McLeod, V.M.; Kelly, B.D.; Sberna, G.; Boyd, B.J.; Williamson, M.; Owen, D.J.; Porter, C.J.H. A comparison of changes to doxorubicin pharmacokinetics, antitumor activity, and toxicity mediated by PEGylated dendrimer and PEGylated liposome drug delivery systems. Nanomed-Nanotechnol., 2012, 8(1), 103-111.
[111]
Gao, Y.; Li, Z.; Xie, X.; Wang, C.; You, J.; Mo, F.; Jin, B.; Chen, J.; Shao, J.; Chen, H.; Jia, L. Dendrimeric anticancer prodrugs for targeted delivery of ursolic acid to folate receptor-expressing cancer cells: Synthesis and biological evaluation. Eur. J. Pharm. Sci., 2015, 70, 55-63.
[112]
Shen, Z.; Li, B.; Liu, Y.; Zheng, G.; Guo, Y.; Zhao, R.; Jiang, K.; Fan, L.; Shao, J. A Self-assembly nanodrug delivery system based on amphiphilic low generations of PAMAM dendrimers-ursolic acid conjugate modified by lactobionic acid for HCC targeting therapy. Nanomedicine , 14(2), 227-236.
[113]
Fan, W.; Shen, B.; Bu, W.; Chen, F.; He, Q.; Zhao, K.; Zhang, S.; Zhou, L.; Peng, W.; Xiao, Q.; Ni, D.; Liu, J.; Shi, J. A smart upconversion-based mesoporous silica nanotheranostic system for synergetic chemo-/radio-/photodynamic therapy and simultaneous MR/UCL imaging. Biomaterials, 2014, 35(32), 8992-9002.
[114]
Li, T.; Chen, X.; Liu, Y.; Fan, L.; Lin, L.; Xu, Y.; Chen, S.; Shao, J. pH-Sensitive mesoporous silica nanoparticles anticancer prodrugs for sustained release of ursolic acid and the enhanced anti-cancer efficacy for hepatocellular carcinoma cancer. Eur. J. Pharm. Sci., 2017, 96, 456-463.
[115]
Jiang, K.; Chi, T.; Li, T.; Zheng, G.; Fan, L.; Liu, Y.; Chen, X.; Chen, S.; Jia, L.; Shao, J. A smart pH-responsive nano-carrier as a drug delivery system for the targeted delivery of ursolic acid: suppresses cancer growth and metastasis by modulating P53/MMP-9/PTEN/CD44 mediated multiple signaling pathways. Nanoscale, 2017, 9(27), 9428-9439.
[116]
Zhao, R.; Li, T.; Zheng, G.; Jiang, K.; Fan, L.; Shao, J. Simultaneous inhibition of growth and metastasis of hepatocellular carcinoma by co-delivery of ursolic acid and sorafenib using lactobionic acid modified and pH-sensitive chitosan-conjugated mesoporous silica nanocomplex. Biomaterials, 2017, 143, 1-16.
[117]
Lopes, S.C.D.; Novais, M.V.M.; Teixeira, C.S.; Honorato-Sampaio, K.; Pereira, M.T.; Ferreira, L.A.M.; Braga, F.C.; Oliveira, M.C. Preparation, physicochemical characterization, and cell viability evaluation of long-circulating and pH-sensitive liposomes containing ursolic acid. BioMed Res. Int., 2013.
[118]
Zheng, G.R.; Shen, Y.L.; Zhao, R.R.; Chen, F.; Zhang, Y.; Xu, A.X.; Shao, J.W. Dual-targeting multifuntional mesoporous silica nanocarrier for codelivery of siRNA and ursolic acid to folate Receptor Overexpressing Cancer Cells. J. Agric. Food Chem., 2017, 65(32), 6904-6911.
[119]
Huang, P.; Wang, D.; Su, Y.; Huang, W.; Zhou, Y.; Cui, D.; Zhu, X.; Yan, D. Combination of small molecule prodrug and nanodrug delivery: amphiphilic drug–drug conjugate for cancer therapy. J. Am. Chem. Soc., 2014, 136(33), 11748-11756.
[120]
Jiang, K.; Han, L.; Guo, Y.; Zheng, G.; Fan, L.; Shen, Z.; Zhao, R.; Shao, J. A carrier-free dual-drug nanodelivery system functionalized with aptamer specific targeting HER2-overexpressing cancer cells. J. Mater. Chem. B , 2017, 5, 9121-9129.
[121]
Guo, Y.; Jiang, K.; Shen, Z.; Zheng, G.; Fan, L.; Zhao, R.; Shao, J. A small molecule nanodrug by self-assembly of dual anticancer drugs and photosensitizer for synergistic near-infrared cancer theranostics. ACS Appl. Mater. Interfaces, 2017, 9(50), 43508-43519.

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