Login Register Cart 0
Review Article

Targeting Protein Kinase Inhibitors with Traditional Chinese Medicine

Author(s): Yangyang Zhang, Minghua Liu, Jun Wang, Jianlin Huang, Mingyue Guo, Ling Zuo, Biantiao Xu, Shousong Cao and Xiukun Lin*

Volume 20, Issue 15, 2019

Page: [1505 - 1516] Pages: 12

DOI: 10.2174/1389450120666190802125959

Price: $65

Abstract

Protein kinases play critical roles in the control of cell growth, proliferation, migration, and angiogenesis, through their catalytic activity. Over the past years, numerous protein kinase inhibitors have been identified and are being successfully used clinically. Traditional Chinese medicine (TCM) represents a large class of bioactive substances, and some of them display anticancer activity via inhibiting protein kinases signal pathway. Some of the TCM have been used to treat tumors clinically in China for many years. The p38mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase, serine/threonine-specific protein kinases (PI3K/AKT/mTOR), and extracellular signal-regulated kinases (ERK) pathways are considered important signals in cancer cell development. In the present article, the recent progress of TCM that exhibited significant inhibitory activity towards a range of protein kinases is discussed. The clinical efficacy of TCM with inhibitory effects on protein kinases in treating a tumor is also presented. The article also discussed the prospects and problems in the development of anticancer agents with TCM.

Keywords: Traditional chinese medicine, protein kinase inhibitors, anticancer activity, PI3K/AKT/mTOR, MAPK, ERK.

Next »
Graphical Abstract

[1]
Sharma PS, Sharma R, Tyagi R. Inhibitors of cyclin dependent kinases: useful targets for cancer treatment. Curr Cancer Drug Targets 2008; 8(1): 53-75.
[http://dx.doi.org/10.2174/156800908783497131] [PMID: 18288944]
[2]
Ferrè F, Palmeri A, Helmer-Citterich M. Computational methods for analysis and inference of kinase/inhibitor relationships. Front Genet 2014; 5: 196-6.
[http://dx.doi.org/10.3389/fgene.2014.00196] [PMID: 25071826]
[3]
Sun ZJ, Chen G, Hu X, et al. Activation of PI3K/Akt/IKK-alpha/NF-kappaB signaling pathway is required for the apoptosis-evasion in human salivary adenoid cystic carcinoma: its inhibition by quercetin. Apoptosis 2010; 15(7): 850-63.
[http://dx.doi.org/10.1007/s10495-010-0497-5] [PMID: 20386985]
[4]
Kannan-Thulasiraman P, Katsoulidis E, Tallman MS, Arthur JS, Platanias LC. Activation of the mitogen- and stress-activated kinase 1 by arsenic trioxide. J Biol Chem 2006; 281(32): 22446-52.
[http://dx.doi.org/10.1074/jbc.M603111200] [PMID: 16762916]
[5]
Chang L, Karin M. Mammalian MAP kinase signalling cascades. Nature 2001; 410(6824): 37-40.
[http://dx.doi.org/10.1038/35065000] [PMID: 11242034]
[6]
Dhanasekaran DN, Reddy EP. JNK signaling in apoptosis. Oncogene 2008; 27(48): 6245-51.
[http://dx.doi.org/10.1038/onc.2008.301] [PMID: 18931691]
[7]
Wagner EF, Nebreda AR. Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer 2009; 9(8): 537-49.
[http://dx.doi.org/10.1038/nrc2694] [PMID: 19629069]
[8]
Sui X, Kong N, Ye L, et al. p38 and JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents. Cancer Lett 2014; 344(2): 174-9.
[http://dx.doi.org/10.1016/j.canlet.2013.11.019] [PMID: 24333738]
[9]
Olson JM, Hallahan AR. p38 MAP kinase: a convergence point in cancer therapy. Trends Mol Med 2004; 10(3): 125-9.
[http://dx.doi.org/10.1016/j.molmed.2004.01.007] [PMID: 15102355]
[10]
Eblen ST. Extracellular-regulated kinases: Signaling from ras to erk substrates to control biological outcomes. Adv Cancer Res 2018; 138: 99-142.
[http://dx.doi.org/10.1016/bs. acr.2018.02.004]
[11]
Nakao Y, Fusetani N. Enzyme inhibitors from marine invertebrates. J Nat Prod 2007; 70(4): 689-710.
[http://dx.doi.org/10.1021/np060600x] [PMID: 17362037]
[12]
Tomeh MA, Hadianamrei R, Zhao X. A review of curcumin and its derivatives as anticancer agents. Int J Mol Sci 2019; 20(5)E1033
[http://dx.doi.org/10.3390/ijms20051033] [PMID: 30818786]
[13]
Lim W, Jeong M, Bazer FW, Song G. Curcumin suppresses proliferation and migration and induces apoptosis on human placental choriocarcinoma cells via erk1/2 and sapk/jnk mapk signaling pathways. Biol Reprod 2016; 95(4): 83.
[http://dx.doi.org/10.1095/biolreprod.116.141630] [PMID: 27580989]
[14]
Yu X, Zhong J, Yan L, et al. Curcumin exerts antitumor effects in retinoblastoma cells by regulating the JNK and p38 MAPK pathways. Int J Mol Med 2016; 38(3): 861-8.
[http://dx.doi.org/10.3892/ijmm.2016.2676] [PMID: 27432244]
[15]
Kanai M, World J J. Therapeutic applications of curcumin for patients with pancreatic cance Gastroenterol 2014; 20(28): 9384-91.
[http://dx.doi.org/10.3748/wjg.v20.i28.9384]
[16]
Yu R, Mandlekar S, Tan TH, Kong AN. Activation of p38 and c-Jun N-terminal kinase pathways and induction of apoptosis by chelerythrine do not require inhibition of protein kinase C. J Biol Chem 2000; 275(13): 9612-9.
[http://dx.doi.org/10.1074/jbc.275.13.9612] [PMID: 10734112]
[17]
Yang R, Piperdi S, Gorlick R. Activation of the RAF/mitogen-activated protein/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase pathway mediates apoptosis induced by chelerythrine in osteosarcoma. Clin Cancer Res 2008; 14(20): 6396-404.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-5113] [PMID: 18927278]
[18]
Zhu Y, Pan Y, Zhang G, et al. Chelerythrine inhibits human hepatocellular carcinoma metastasis in vitro. Biol Pharm Bull 2018; 41(1): 36-48.
[19]
Jana J, Mondal S, Bhatttacharjee P, et al. Chelerythrine down regulates expression of VEGFA, BCL2 and KRAS by arresting G-Quadruplex structures at their promoter regions. Sci Rep 2017; 7: 40706-11.
[20]
Hao W, Wang S, and Zhou Z. Tubeimoside-1 (TBMS1) inhibits lung cancer cell growth and induces cells apoptosis through activation of MAPK-JNK pathway. Int J Clin Exp Pathol 2015; 8(10): 12075-83.
[PMID: 26722392]
[21]
Chen L, Weng Q, Li F, Liu J, Zhang X, Zhou Y. Pharmacokinetics and bioavailability study of tubeimoside-I in ICR mice by UPLC-MS/MS. J Anal Methods Chem 2018; 20189074893
[http://dx.doi.org/10.1155/2018/9074893] [PMID: 30116651]
[22]
Peng B, Xu L, Cao F, et al. HSP90 inhibitor, celastrol, arrests human monocytic leukemia cell U937 at G0/G1 in thiol-containing agents reversible way. Mol Cancer 2010; 9: 79.
[http://dx.doi.org/10.1186/1476-4598-9-79] [PMID: 20398364]
[23]
Kannaiyan R, Manu KA, Chen L, et al. Celastrol inhibits tumor cell proliferation and promotes apoptosis through the activation of c-Jun N-terminal kinase and suppression of PI3 K/Akt signaling pathways. Apoptosis 2011; 16(10): 1028-41.
[http://dx.doi.org/10.1007/s10495-011-0629-6] [PMID: 21786165]
[24]
Sethi G, Ahn KS, Pandey MK, Aggarwal BB. Celastrol, a novel triterpene, potentiates TNF-induced apoptosis and suppresses invasion of tumor cells by inhibiting NF-kappaB-regulated gene products and TAK1-mediated NF-kappaB activation. Blood 2007; 109(7): 2727-35.
[PMID: 17110449]
[25]
Yang H, Chen D, Cui QC, Yuan X, Dou QP. Celastrol, a triterpene extracted from the Chinese “Thunder of God Vine,” is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice. Cancer Res 2006; 66(9): 4758-65.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-4529] [PMID: 16651429]
[26]
Rajendran P, Li F, Shanmugam MK, et al. Celastrol suppresses growth and induces apoptosis of human hepatocellular carcinoma through the modulation of STAT3/JAK2 signaling cascade in vitro and in vivo. Cancer Prev Res (Phila) 2012; 5(4): 631-43.
[http://dx.doi.org/10.1158/1940-6207.CAPR-11-0420] [PMID: 22369852]
[27]
Huang Y, Zhou Y, Fan Y, Zhou D. Celastrol inhibits the growth of human glioma xenografts in nude mice through suppressing VEGFR expression. Cancer Lett 2008; 264(1): 101-6.
[http://dx.doi.org/10.1016/j.canlet.2008.01.043] [PMID: 18343027]
[28]
Lee JH, Won YS, Park KH, et al. Celastrol inhibits growth and induces apoptotic cell death in melanoma cells via the activation ROS-dependent mitochondrial pathway and the suppression of PI3K/AKT signaling. Apoptosis 2012; 17(12): 1275-86.
[http://dx.doi.org/10.1007/s10495-012-0767-5] [PMID: 23065091]
[29]
Li HY, Zhang J, Sun LL, et al. Celastrol induces apoptosis and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells: an in vitro and in vivo study. Cell Death Dis 2015; 6e: 1604.
[http://dx.doi.org/10.1038/cddis.2014.543] [PMID: 25611379]
[30]
Lin FZ, Wang SC, Hsi YT, et al. Celastrol induces vincristine multidrug resistance oral cancer cell apoptosis by targeting JNK1/2 signaling pathway. Phytomedicine 2019; 54(54): 1-8.
[http://dx.doi.org/10.1016/j.phymed.2018.09.181] [PMID: 30668359]
[31]
Li X, Zhu G, Yao X, et al. Celastrol induces ubiquitin-dependent degradation of mTOR in breast cancer cells. OncoTargets Ther 2018; 11(11): 8977-85.
[http://dx.doi.org/10.2147/OTT.S187315] [PMID: 30588010]
[32]
Pang X, Yi Z, Zhang J, et al. Correction: Celastrol suppresses Angiogenesis-mediated tumor growth through inhibition of AKT/Mammalian target of rapamycin pathway. Cancer Res 2019; 79(3): 685.
[http://dx.doi.org/10.1158/0008-5472.CAN-18-3859] [PMID: 30709873]
[33]
Wang G, Xiao Q, Wu Y, et al. Design and synthesis of novel celastrol derivative and its antitumor activity in hepatoma cells and antiangiogenic activity in zebrafish. J Cell Physiol 2019; 15.
[http://dx.doi.org/10.1002/jcp.28312] [PMID: 30770566]
[34]
Qu W, Wang Y, Wu Q, Liu J, Hao D. Emodin inhibits HMGB1-induced tumor angiogenesis in human osteosarcoma by regulating SIRT1. Int J Clin Exp Med 2015; 8(9): 15054-64.
[PMID: 26628989]
[35]
Ma L, Li W. Emodin inhibits LOVO colorectal cancer cell proliferation via the regulation of the Bcl-2/Bax ratio and cytochrome c. Exp Ther Med 2014; 8(4): 1225-8.
[http://dx.doi.org/10.3892/etm.2014.1900] [PMID: 25187829]
[36]
Lin W, Zhong M, Yin H, et al. Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo. Oncol Rep 2016; 36(2): 961-7.
[http://dx.doi.org/10.3892/or.2016.4861] [PMID: 27278720]
[37]
Lin W, Zhong M, Yin H, et al. Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo. Oncol Rep 2016; 36(2): 961-7.
[http://dx.doi.org/10.3892/or.2016.4861] [PMID: 27278720]
[38]
Yu J, Guo X, Zhang Q, Peng Y, Zheng J. Metabolite profile analysis and pharmacokinetic study of emodin, baicalin and geniposide in rats. Xenobiotica 2018; 48(9): 927-37.
[http://dx.doi.org/10.1080/00498254.2017.1382748] [PMID: 28967290]
[39]
Song Y, Sheng Z, Xu Y, et al. Magnetic liposomal emodin composite with enhanced killing efficiency against breast cancer. Biomater Sci 2019; 7(3): 867-75.
[http://dx.doi.org/dx.doi: 10.1039/c8bm01530a] [PMID: 30648710]
[40]
Song Y, Sheng Z, Xu Y, et al. Magnetic liposomal emodin composite with enhanced killing efficiency against breast cancer. Biomater Sci 2019.
[http://dx.doi.org/10.1039/C8BM01530A]
[41]
Zhang J, Wang F, Wang H, et al. Paeoniflorin inhibits proliferation of endometrial cancer cells via activating MAPK and NF-κB signaling pathways. Exp Ther Med 2017; 14(6): 5445-51.
[http://dx.doi.org/10.3892/etm.2017.5250] [PMID: 29285074]
[42]
Zheng F, Tang Q, Wu J, et al. p38α MAPK-mediated induction and interaction of FOXO3a and p53 contribute to the inhibited-growth and induced-apoptosis of human lung adenocarcinoma cells by berberine. J Exp Clin Cancer Res 2014; 33(1): 36.
[http://dx.doi.org/10.1186/1756-9966-33-36] [PMID: 24766860]
[43]
Yu L, Wang L, Chen S. Dual character of Toll-like receptor signaling: pro-tumorigenic effects and anti-tumor functions. Biochim Biophys Acta 2013; 1835(2): 144-54.
[PMID: 23232186]
[44]
LoPiccolo J, Granville CA, Gills JJ, Dennis PA. Targeting Akt in cancer therapy. Anticancer Drugs 2007; 18(8): 861-74.
[PMID: 17667591]
[45]
Crowell JA, Steele VE, Fay JR. Targeting the AKT protein kinase for cancer chemoprevention. Mol Cancer Ther 2007; 6(8): 2139-48.
[http://dx.doi.org/10.1158/1535-7163.MCT-07-0120] [PMID: 17699713]
[46]
Brown VI, Fang J, Alcorn K, et al. Rapamycin is active against B-precursor leukemia in vitro and in vivo, an effect that is modulated by IL-7-mediated signaling. Proc Natl Acad Sci USA 2003; 100(25): 15113-8.
[http://dx.doi.org/10.1073/pnas.2436348100] [PMID: 14657335]
[47]
Wei X, Si N, Zhang Y, et al. Evaluation of bufadienolides as the main antitumor components in cinobufacin injection for liver and gastraic cancer therapy. Plos one eCollection 2017 2017; 12(1) eo169141
[http://dx.doi.org/101371/journal.pone. 0169141]
[48]
Xie RF, Li ZC, Gao B, Shi ZN, Zhou X. Bufothionine, a possible effective component in cinobufocini injection for hepatocellular carcinoma. J Ethnopharmacol 2012; 141(2): 692-700.
[http://dx.doi.org/10.1016/j.jep.2011.12.018] [PMID: 22210051]
[49]
Teachey DT, Obzut DA, Cooperman J, et al. The mTOR inhibitor CCI-779 induces apoptosis and inhibits growth in preclinical models of primary adult human ALL. Blood 2006; 107(3): 1149-55.
[http://dx.doi.org/10.1182/blood-2005-05-1935] [PMID: 16195324]
[50]
Chen G, Hu X, Zhang W, et al. Mammalian target of rapamycin regulates isoliquiritigenin-induced autophagic and apoptotic cell death in adenoid cystic carcinoma cells. Apoptosis 2012; 17(1): 90-101.
[http://dx.doi.org/10.1007/s10495-011-0658-1] [PMID: 21956714]
[51]
Zhang X, Yuan Y, Xi Y, et al. Cinobufacini injection improves the efficancy of chemotherapy on advanced stage gastric cancer:a systemic review and meta-analysis. Evid Based Complement Alternat Med eCollection 2018; 7362340.
[http://dx.doi.org/10.1155/2018/7362340]
[52]
Li QQ, Wang G, Zhang M, Cuff CF, Huang L, Reed E. beta-Elemene, a novel plant-derived antineoplastic agent, increases cisplatin chemosensitivity of lung tumor cells by triggering apoptosis. Oncol Rep 2009; 22(1): 161-70.
[http://dx.doi.org/10.3892/or_00000420] [PMID: 19513519]
[53]
Xia J, Inagaki Y, Gao J, et al. Combination of Cinobufacini and Doxorubicin Increases Apoptosis of Hepatocellular Carcinoma Cells through the Fas- and Mitochondria-Mediated Pathways. Am J Chin Med 2017; 45(7): 1537-56.
[http://dx.doi.org/10.1142/S0192415X17500835] [PMID: 28946772]
[54]
Li QQ, Wang G, Zhang M, Cuff CF, Huang L, Reed E. beta-Elemene, a novel plant-derived antineoplastic agent, increases cisplatin chemosensitivity of lung tumor cells by triggering apoptosis. Oncol Rep 2009; 22(1): 161-70.
[http://dx.doi.org/10.3892/or_00000420] [PMID: 19513519]
[55]
Wang G, Li X, Huang F, et al. Antitumor effect of beta-elemene in non-small-cell lung cancer cells is mediated via induction of cell cycle arrest and apoptotic cell death. Cell Mol Life Sci 2005; 62(7-8): 881-93.
[http://dx.doi.org/10.1007/s00018-005-5017-3] [PMID: 15868411]
[56]
Xie CY, Yang W, Li M, et al. Cell apoptosis induced by delta-elemene in colorectal adenocarcinoma cells via a mitochondrial-mediated pathway. Yakugaku Zasshi 2009; 129(11): 1403-13.
[http://dx.doi.org/10.1248/yakushi.129.1403] [PMID: 19881213]
[57]
Yao YQ, Ding X, Jia YC, Huang CX, Wang YZ, Xu YH. Anti-tumor effect of beta-elemene in glioblastoma cells depends on p38 MAPK activation. Cancer Lett 2008; 264(1): 127-34.
[http://dx.doi.org/10.1016/j.canlet.2008.01.049] [PMID: 18442668]
[58]
Tan P, Zhong W, Cai W. Clinical study on treatment of 40 cases of malignant brain tumor by elemene emulsion injection. Zhongguo Zhong Xi Yi Jie He Za Zhi 2000; 20(9): 645-8.
[PMID: 11789165]
[59]
Liu J, Zhang Y, Qu J, et al. β-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis. BMC Cancer 2011; 11: 183-3.
[http://dx.doi.org/10.1186/1471-2407-11-183] [PMID: 21595977]
[60]
Zhang W, Chen L, Geng J, Liu L, Xu L. β-elemene inhibits oxygen-induced retinal neovascularization via promoting miR-27a and reducing VEGF expression. Mol Med Rep 2019; 19(3): 2307-16.
[http://dx.doi.org/10.3892/mmr.2019.9863] [PMID: 30664207]
[61]
Cheng H, Ge X, Zhuo S, et al. β-Elemene synergizes with gefitinib to inhibit stem-like phenotypes and progression of lung cancer via down-regulating EZH2. Front Pharmacol 2018; 9(9): 1413.
[http://dx.doi.org/10.3389/fphar.2018.01413] [PMID: 30555330]
[62]
Guo Z, Liu Z, Yue H, Wang J. Beta-elemene increases chemosensitivity to 5-fluorouracil through down-regulating microRNA-191 expression in colorectal carcinoma cells. J Cell Biochem 2018; 119(8): 7032-9.
[http://dx.doi.org/10.1002/jcb.26914] [PMID: 29737579]
[63]
Zhang J, Wang F, Wang H, et al. Paeoniflorin inhibits proliferation of endometrial cancer cells via activating MAPK and NF-κB signaling pathways. Exp Ther Med 2017; 14(6): 5445-51.
[http://dx.doi.org/10.3892/etm.2017.5250] [PMID: 29285074]
[64]
Piotrowska H, Kucinska M, Murias M. Biological activity of piceatannol: leaving the shadow of resveratrol. Mutat Res 2012; 750(1): 60-82.
[http://dx.doi.org/10.1016/j.mrrev.2011.11.001] [PMID: 22108298]
[65]
Kucinska M, Piotrowska H, Luczak MW, et al. Effects of hydroxylated resveratrol analogs on oxidative stress and cancer cells death in human acute T cell leukemia cell line: prooxidative potential of hydroxylated resveratrol analogs. Chem Biol Interact 2014; 209: 96-110.
[http://dx.doi.org/10.1016/j.cbi.2013.12.009] [PMID: 24398169]
[66]
Jing X, Cheng W, Wang S, Li P, He L. Resveratrol induces cell cycle arrest in human gastric cancer MGC803 cells via the PTEN-regulated PI3K/Akt signaling pathway. Oncol Rep 2016; 35(1): 472-8.
[http://dx.doi.org/10.3892/or.2015.4384] [PMID: 26530632]
[67]
Mineda A, Nishimura M, Kagawa T, et al. Resveratrol suppresses proliferation and induces apoptosis of uterine sarcoma cells by inhibiting the Wnt signaling pathway. Exp Ther Med 2019; 17(3): 2242-6.
[http://dx.doi.org/10.3892/etm.2019.7209] [PMID: 30867708]
[68]
Berman AY, Motechin RA, Wiesenfeld MY, HolZ MK. The therapeutic potentical of resveratrol: a review of clinical trails Npj Precisiononcol 2017; 35.
[http://dx.doi.org/101038/s41698-017-0038-6]
[69]
Kjaer TN, Ornstrup MJ, Poulsen MM, et al. Resveratrol reduces the levels of circulating androgen precursors but has no effect on, testosterone, dihydrotestosterone, PSA levels or prostate volume. A 4-month randomised trial in middle-aged men. Prostate 2015; 75(12): 1255-63.
[http://dx.doi.org/10.1002/pros.23006] [PMID: 25939591]
[70]
Lian B, Wu M, Feng Z, Deng Y, Zhong C, Zhao X. Folate-conjugated human serum albumin-encapsulated resveratrol nanoparticles: preparation, characterization, bioavailability and targeting of liver tumors. Artif Cells Nanomed Biotechnol 2019; 47(1): 154-65.
[http://dx.doi.org/10.1080/21691401.2018.1548468] [PMID: 30686050]
[71]
Moradzadeh M, Sadeghnia HR, Tabarraei A, Sahebkar A. Anti-tumor effects of crocetin and related molecular targets. J Cell Physiol 2018; 233(3): 2170-82.
[http://dx.doi.org/10.1002/jcp.25953] [PMID: 28407293]
[72]
Li S, Qu Y, Shen XY, et al. Multiple signal pathways involved in crocetin-induced apoptosis in KYSE-150 cells. Pharmacol 2019; 103(5-6): 263-72.
[http://dx.doi.org/10.1159/000487956] [PMID: 30783055]
[73]
Moradzadeh M, Sadeghnia HR, Tabarraei A, Sahebkar A. Anti-tumor effects of crocetin and related molecular targets. J Cell Physiol 2017; 233(3): 2170-82.
[74]
Arzi L, Riazi G, Sadeghizadeh M, Hoshyar R, Jafarzadeh N. A comparative study on Anti-invasion, antimigration, and antiadhesion effects of the bioactive carotenoids of saffron on 4T1 breast cancer cells through their effects on Wnt/β-catenin pathway genes. DNA Cell Biol 2018; 37(8): 697-707.
[PMID: 29969282]
[75]
Wang CZ, McEntee E, Wicks S, Wu JA, Yuan CS. Phytochemical and analytical studies of Panax notoginseng(Burk.) F.H. Chen. J Nat Med 2006; 60: 97-106.
[http://dx.doi.org/10.1007/s11418-005-0027-x]
[76]
Li L, Sun JX, Wang XQ, et al. Notoginsenoside R7 suppresses cervical cancer via PI3K/PTEN/Akt/mTOR signaling. Oncotarget 2017; 8(65): 109487-96.
[http://dx.doi.org/10.18632/oncotarget.22721] [PMID: 29312623]
[77]
Jang HS, Kook SH, Son YO, et al. Flavonoids purified from Rhus verniciflua Stokes actively inhibit cell growth and induce apoptosis in human osteosarcoma cells. Biochim Biophys Acta 2005; 1726(3): 309-16.
[http://dx.doi.org/10.1016/j.bbagen.2005.08.010] [PMID: 16213662]
[78]
Sun X, Ma X, Li Q, et al. Anti-cancer effects of fisetin on mammary carcinoma cells via regulation of the PI3K/Akt/mTOR pathway: In vitro and in vivo studies. Int J Mol Med 2018; 42(2): 811-20.
[http://dx.doi.org/10.3892/ijmm.2018.3654] [PMID: 29749427]
[79]
Sigismund S, Avanzato D, Lanzetti L. Emerging functions of the EGFR in cancer. Mol Oncol 2018; 12(1): 3-20.
[http://dx.doi.org/10.1002/1878-0261.12155] [PMID: 29124875]
[80]
He BC, Gao JL, Luo X, et al. Ginsenoside Rg3 inhibits colorectal tumor growth through the down-regulation of Wnt/ß-catenin signaling. Int J Oncol 2011; 38(2): 437-45.
[http://dx.doi.org/10.3892/ijo.2010.858] [PMID: 21152855]
[81]
Lu P, Su W, Miao ZH, Niu HR, Liu J, Hua QL. Effect and mechanism of ginsenoside Rg3 on postoperative life span of patients with non-small cell lung cancer. Chin J Integr Med 2008; 14(1): 33-6.
[http://dx.doi.org/10.1007/s11655-007-9002-6] [PMID: 18219455]
[82]
Nakhjavani M, Hardingham JE, Palethorpe HM, et al. Ginsenoside Rg3: potential molecular targets and therapeutic indication in metastatic breast cancer. Medicines (Basel) 2019; 6(1)E17
[http://dx.doi.org/10.3390/medicines6010017] [PMID: 30678106]
[83]
Shan X, Aziz F, Tian LL, Wang XQ, Yan Q, Liu JW. Ginsenoside Rg3-induced EGFR/MAPK pathway deactivation inhibits melanoma cell proliferation by decreasing FUT4/LeY expression. Int J Oncol 2015; 46(4): 1667-76.
[http://dx.doi.org/10.3892/ijo.2015.2886] [PMID: 25672851]
[84]
Peng Y, Zhang R, Yang X, et al. Ginsenoside Rg3 suppresses the proliferation of prostate cancer cell line PC3 through ROS-induced cell cycle arrest. Oncol Lett 2019; 17(1): 1139-45.
[PMID: 30655875]
[85]
Cao Y, Ye Q, Zhuang M, et al. Ginsenoside Rg3 inhibits angiogenesis in a rat model of endometriosis through the VEGFR-2-mediated PI3K/Akt/mTOR signaling pathway. PLoS One 2017; 12(11)e0186520
[http://dx.doi.org/10.1371/journal.pone.0186520] [PMID: 29140979]
[86]
Zhao Q, Li P, Jiang J, Hu P. Pharmacokinetics of single ascending doses and multiple doses of 20 (S)-ginsenoside Rg3 in Chinese healthy volunteers. Eur J Drug Metab Pharmacokinet 2016; 41(6): 845-53.
[http://dx.doi.org/10.1007/s13318-015-0304-3] [PMID: 26470874]
[87]
Park EJ, Min HY, Chung HJ, et al. Down-regulation of c-Src/EGFR-mediated signaling activation is involved in the honokiol-induced cell cycle arrest and apoptosis in MDA-MB-231 human breast cancer cells. Cancer Lett 2009; 277(2): 133-40.
[http://dx.doi.org/10.1016/j.canlet.2008.11.029] [PMID: 19135778]
[88]
Tang H, Zhang Y, Li D, et al. Discovery and synthesis of novel magnolol derivatives with potent anticancer activity in non-small cell lung cancer. Eur J Med Chem 2018; 156(156): 190-205.
[http://dx.doi.org/10.1016/j.ejmech.2018.06.048] [PMID: 30006164]
[89]
Huang K, Chen Y, Zhang R, et al. Honokiol induces apoptosis and autophagy via the ROS/ERK1/2 signaling pathway in human osteosarcoma cells in vitro and in vivo. Cell Death Dis 2018; 9(2): 157.
[http://dx.doi.org/10.1038/s41419-017-0166-5] [PMID: 29410403]
[90]
Yang J, Zou Y, Jiang D. Honokiol suppresses proliferation and induces apoptosis via regulation of the miR-21/PTEN/PI3K/AKT signaling pathway in human osteosarcoma cells. Int J Mol Med 2018; 41(4): 1845-54.
[http://dx.doi.org/10.3892/ijmm.2018.3433] [PMID: 29393336]
[91]
Li Z, Dong H, Li M, et al. Honokiol induces autophagy and apoptosis of osteosarcoma through PI3K/Akt/mTOR signaling pathway. Mol Med Rep 2018; 17(2): 2719-23.
[PMID: 29207060]
[92]
Fan Y, Mao Y, Cao S, et al. S5, a whithanolide isolated from physalis pubescens L., induces G2/M cell cycle arrest via the EGFR/p38 pathway in human melanoma A375 cells. Molecules 2018; 23(12)e3175
[http://dx.doi.org/10.3390/molecules23123175] [PMID: 30513793]
[93]
Lu MK, Lin TY, Chang CC. Chemical identification of a sulfated glucan from Antrodia cinnamomea and its anti-cancer functions via inhibition of EGFR and mTOR activity. Carbohydr Polym 2018; 202(202): 536-44.
[http://dx.doi.org/10.1016/j.carbpol.2018.09.009] [PMID: 30287033]
[94]
Yin JH, Zhu XY, Shi WD, Liu LM. Huachansu injection inhibits metastasis of pancreatic cancer in mice model of human tumor xenograft. BMC Complement Altern Med 2014; 14(14): 483.
[http://dx.doi.org/10.1186/1472-6882-14-483] [PMID: 25496480]
[95]
Wang Y, Zhang C1, Zhang S, et al. Kanglaite sensitizes colorectal cancer cells to Taxol via NF-κB inhibition and connexin 43 upregulation. Sci Rep 2017; 7(1): 1280.
[http://dx.doi.org/10.1038/s41598-017-01480-2] [PMID: 28455529]
[96]
Bing Z, Cheng Z, Shi D, et al. Investigate the mechanisms of Chinese medicine Fuzhengkangai towards EGFR mutation-positive lung adenocarcinomas by network pharmacology. BMC Complement Altern Med 2018; 18(1): 293.
[http://dx.doi.org/10.1186/s12906-018-2347-x] [PMID: 30400936]
[97]
Liu X, Yang Q, Xi Y, et al. Kanglaite injection combined with chemotherapy versus chemotherapy alone in the treatment of advanced non-small cell lung carcinoma. J Cancer Res Ther 2014; 10(Suppl. 1): 46-51.
[http://dx.doi.org/10.4103/0973-1482.139758] [PMID: 25207891]
[98]
Zhang D, Wu J, Wang K, Duan X, Liu S, Zhang B. Which are the best Chinese herbal injections combined with XEIOX regimen for gastric cancer:A PRISMA-compliant network meta-analysis. Medicine 2018; 97(12)e0127
[http://dx.doi.org/10.1097/MD. 0000000000010127]
[99]
Liu M, Zhao G, Zhang D, et al. Active fraction of clove induces apoptosis via PI3K/Akt/mTOR-mediated autophagy in human colorectal cancer HCT-116 cells. Int J Oncol 2018; 53(3): 1363-73.
[http://dx.doi.org/10.3892/ijo.2018.4465] [PMID: 30015913]
[100]
Liu H, Schmitz JC, Wei J, et al. Clove extract inhibits tumor growth and promotes cell cycle arrest and apoptosis. Oncol Res 2014; 21(5): 247-59.
[http://dx.doi.org/10.3727/096504014X13946388748910] [PMID: 24854101]
[101]
Cao Y, Ye Q, Zhuang M, et al. Ginsenoside Rg3 inhibits angiogenesis in a rat model of endometriosis through the VEGFR-2-mediated PI3K/Akt/mTOR signaling pathway. PLoS One 2017; 12(11)e0186520
[http://dx.doi.org/10.1371/journal.pone.0186520] [PMID: 29140979]
[102]
An SY, Youn GS, Kim H, Choi SY, Park J. Celastrol suppresses expression of adhesion molecules and chemokines by inhibiting JNK-STAT1/NF-κB activation in poly(I:C)-stimulated astrocytes. BMB Rep 2017; 50(1): 25-30.
[http://dx.doi.org/10.5483/BMBRep.2017.50.1.114] [PMID: 28027722]

Rights & Permissions Print Cite
Article Metrics
46
3
1
1
© 2024 Bentham Science Publishers | Privacy Policy