Anticancer effect and molecular mechanism of ginsenoside Rg3 in various cancer types
Yuzhu Wang, Guoping Li, Tingting Chen, Wei Wu, Zhiping Yan, Xiaoyu Li
Anticancer effect and molecular mechanism of ginsenoside Rg3 in various cancer types
Ginsenoside Rg3 (Rg3), extracted from the root of Panax ginseng, is one of the most abundant ginsenosides. Rg3 exhibits anticancer activity in various cancer models in vitro and in vivo by modulating several signaling pathways, such as those of phosphatidylinositol 3-kinase, epidermal growth factor receptor, mitogen-activated protein kinases, p53, nuclear factor kappa-B, and reactive oxygen species. Besides, Rg3 can be used as adjunctive with conventional anticancer therapies, enhancing therapeutic effects and reversing drug resistance in cancer therapy. So, the purpose of this review is to provide a systematic summary and analysis the anticancer effects and the potential mechanisms of Rg3 extracted from ginseng.
Ginsenoside Rg3 / Panax ginseng / Anticancer / Molecular mechanism
[1] |
Miao XS, Metcalfe CD, Hao C, March RE. Electrospray ionization mass spectrometry of ginsenosides. J Mass Spectrom: JMS. 2002; 37: 495- 506.
|
[2] |
Hou M, Wang R, Zhao S, Wang Z. Ginsenosides in Panax genus and their biosynthesis. Acta Pharm Sin B. 2021; 11: 1813- 1834.
|
[3] |
Lelu JK, Liu Q, Alolga RN, et al. A new two-dimensional chromatographic method for separation of saponins from steamed Panax notoginseng. J Pharmaceut Biomed Anal. 2016; 125: 355- 359.
|
[4] |
Mohanan P, Subramaniyam S, Mathiyalagan R, Yang DC. Molecular signaling of ginsenosides Rb1, Rg1, and Rg3 and their mode of actions. J Ginseng Res. 2018; 42: 123- 132.
|
[5] |
Nakhjavani M, Smith E, Townsend AR, Price TJ, Hardingham JE. Anti-Angiogenic Properties of Ginsenoside Rg3. Basel, Switzerland: Molecules; 2020:25.
|
[6] |
Liu Z, Liu T, Li W, Li J, Wang C, Zhang K. Insights into the antitumor mechanism of ginsenosides Rg3. Mol Biol Rep. 2021; 48: 2639- 2652.
|
[7] |
He B, Chen P, Yang J, et al. Neuroprotective effect of 20(R)-ginsenoside Rg(3) against transient focal cerebral ischemia in rats. Neurosci Lett. 2012; 526: 106- 111.
|
[8] |
Wei X, Chen J, Su F, Su X, Hu T, Hu S. Stereospecificity of ginsenoside Rg3 in promotion of the immune response to ovalbumin in mice. Int Immunol. 2012; 24: 465- 471.
|
[9] |
Wei X, Su F, Su X, Hu T, Hu S. Stereospecific antioxidant effects of ginsenoside Rg3 on oxidative stress induced by cyclophosphamide in mice. Fitoterapia. 2012; 83: 636- 642.
|
[10] |
Wu K, Li N, Sun H, Xu T, Jin F, Nie J. Endoplasmic reticulum stress activation mediates Ginseng Rg3-induced anti-gallbladder cancer cell activity. Biochem Biophys Res Commun. 2015; 466: 369- 375.
|
[11] |
Pu Z, Ge F, Wang Y, et al. Ginsenoside-Rg3 inhibits the proliferation and invasion of hepatoma carcinoma cells via regulating long non-coding RNA HOX antisense intergenic. Bioengineered. 2021; 12: 2398- 2409.
|
[12] |
Li Y, Lu J, Bai F, Xiao Y, Guo Y, Dong Z. Ginsenoside Rg3 suppresses proliferation and induces apoptosis in human osteosarcoma. BioMed Res Int. 2018, 4306579, 2018.
|
[13] |
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: 1667- 1676.
|
[14] |
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: 1139- 1145.
|
[15] |
Ham J, Lee S, Lee H, Jeong D, Park S, Kim SJ. Genome-wide methylation analysis identifies NOX4 and KDM5A as key regulators in inhibiting breast cancer cell proliferation by ginsenoside Rg3. Am J Chin Med. 2018; 46: 1333- 1355.
|
[16] |
Xie Q, Wen H, Zhang Q, et al. Inhibiting PI3K-AKt signaling pathway is involved in antitumor effects of ginsenoside Rg3 in lung cancer cell. Biomed pharmacother = Biomed pharmacother. 2017; 85: 16- 21.
|
[17] |
Mao X, Jin Y, Feng T, et al. Ginsenoside Rg3 inhibits the growth of osteosarcoma and attenuates metastasis through the wnt/β-catenin and EMT signaling pathway. Evid base Compl Alternative Med: eCAM. 2020, 6065124, 2020.
|
[18] |
Liu T, Zuo L, Guo D, et al. Ginsenoside Rg3 regulates DNA damage in non-small cell lung cancer cells by activating VRK1/P53BP1 pathway. Biomed pharmacother = Biomed pharmacother. 2019;120, 109483.
|
[19] |
Shan X, Fu YS, Aziz F, Wang XQ, Yan Q, Liu JW. Ginsenoside Rg3 inhibits melanoma cell proliferation through down-regulation of histone deacetylase 3 (HDAC3) and increase of p53 acetylation. PLoS One. 2014;9, e115401.
|
[20] |
Meng L, Ji R, Dong X, Xu X, Xin Y, Jiang X. Antitumor activity of ginsenoside Rg3 in melanoma through downregulation of the ERK and Akt pathways. Int J Oncol. 2019; 54: 2069- 2079.
|
[21] |
Zhao L, Sun W, Zheng A, Zhang Y, Fang C, Zhang P. Ginsenoside Rg3 suppresses ovarian cancer cell proliferation and invasion by inhibiting the expression of lncRNA H19. Acta Biochim Pol. 2021; 68: 575- 582.
|
[22] |
Liu W, Pan HF, Yang LJ, et al. Panax ginseng C.A. Meyer (Rg3) ameliorates gastric precancerous lesions in Atp4a(-/-) mice via inhibition of glycolysis through PI3K/AKT/miRNA-21 pathway. Evid base Compl Alternative Med: eCAM. 2020, 2672648, 2020.
|
[23] |
Liu W, Zhang SX, Ai B, et al. Ginsenoside Rg3 promotes cell growth through activation of mTORC1. Front Cell Dev Biol. 2021;9, 730309.
|
[24] |
Zhang F, Li M, Wu X, et al. 20(S)-ginsenoside Rg3 promotes senescence and apoptosis in gallbladder cancer cells via the p53 pathway. Drug Des Dev Ther. 2015; 9: 3969- 3987.
|
[25] |
Park HM, Kim SJ, Kim JS, Kang HS. Reactive oxygen species mediated ginsenoside Rg3- and Rh2-induced apoptosis in hepatoma cells through mitochondrial signaling pathways. Food Chem Toxicol: Int J Publ British Ind Biol Res Ass. 2012; 50: 2736- 2741.
|
[26] |
Bian S, Zhao Y, Li F, et al. 20(S)-Ginsenoside Rg3 Promotes HeLa Cell Apoptosis by Regulating Autophagy. Basel, Switzerland: Molecules; 2019:24.
|
[27] |
Lee JY, Jung KH, Morgan MJ, et al. Sensitization of TRAIL-induced cell death by 20(S)-ginsenoside Rg3 via CHOP-mediated DR5 upregulation in human hepatocellular carcinoma cells. Mol Cancer Therapeut. 2013; 12: 274- 285.
|
[28] |
Wu K, Huang J, Li N, Xu T, Cai W, Ye Z. Antitumor effect of ginsenoside Rg3 on gallbladder cancer by inducing endoplasmic reticulum stress-mediated apoptosis in vitro and in vivo. Oncol Lett. 2018; 16: 5687- 5696.
|
[29] |
Hwang SK, Jeong YJ, Cho HJ, Park YY, Song KH, Chang YC. Rg3-enriched red ginseng extract promotes lung cancer cell apoptosis and mitophagy by ROS production. J Ginseng Res. 2022; 46: 138- 146.
|
[30] |
Kim BM, Kim DH, Park JH, Na HK, Surh YJ. Ginsenoside Rg3 induces apoptosis of human breast cancer (MDA-MB-231) cells. J Cancer Prevent. 2013; 18: 177- 185.
|
[31] |
Sin S, Kim SY, Kim SS. Chronic treatment with ginsenoside Rg3 induces Akt-dependent senescence in human glioma cells. Int J Oncol. 2012; 41: 1669- 1674.
|
[32] |
Kim BJ, Nah SY, Jeon JH, So I, Kim SJ. Transient receptor potential melastatin 7 channels are involved in ginsenoside Rg3-induced apoptosis in gastric cancer cells. Basic Clin Pharmacol Toxicol. 2011; 109: 233- 239.
|
[33] |
Zhang YH, Li HD, Li B, Jiang SD, Jiang LS. Ginsenoside Rg3 induces DNA damage in human osteosarcoma cells and reduces MNNG-induced DNA damage and apoptosis in normal human cells. Oncol Rep. 2014; 31: 919- 925.
|
[34] |
Li X, Tsauo J, Geng C, Zhao H, Lei X, Li X. Ginsenoside Rg3 decreases NHE1 expression via inhibiting EGF-EGFR-ERK1/2-HIF-1 α pathway in hepatocellular carcinoma: a novel antitumor mechanism. Am J Chin Med. 2018; 46: 1915- 1931.
|
[35] |
Li J, Qi Y. Ginsenoside Rg3 inhibits cell growth, migration and invasion in Caco-2 cells by downregulation of lncRNA CCAT1. Exp Mol Pathol. 2019; 106: 131- 138.
|
[36] |
Wang JH, Nao JF, Zhang M, He P. 20(s)-ginsenoside Rg3 promotes apoptosis in human ovarian cancer HO-8910 cells through PI3K/Akt and XIAP pathways. Tumour Biol: J Int Soc Oncodevelopment Biol Med. 2014; 35: 11985- 11994.
|
[37] |
Yang Q, Cai N, Che D, Chen X, Wang D. Ginsenoside Rg3 inhibits the biological activity of SGC-7901. Food Sci Nutr. 2020; 8: 4151- 4158.
|
[38] |
Choi YJ, Lee HJ, Kang DW, Han IH, Choi BK, Cho WH. Ginsenoside Rg3 induces apoptosis in the U87MG human glioblastoma cell line through the MEK signaling pathway and reactive oxygen species. Oncol Rep. 2013; 30: 1362- 1370.
|
[39] |
Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature. 2008; 451: 1069- 1075.
|
[40] |
Zheng X, Chen W, Hou H, et al. Ginsenoside 20(S)-Rg3 induced autophagy to inhibit migration and invasion of ovarian cancer. Biomed pharmacother = Biomed pharmacother. 2017; 85: 620- 626.
|
[41] |
Liang Y, Zhang T, Jing S, et al. 20(S)-Ginsenoside Rg3 inhibits lung cancer cell proliferation by targeting EGFR-mediated ras/raf/MEK/ERK pathway. Am J Chin Med. 2021; 49: 753- 765.
|
[42] |
Nakhjavani M, Hardingham JE, Palethorpe HM, et al. Ginsenoside Rg3: Potential Molecular Targets and Therapeutic Indication in Metastatic Breast Cancer. Basel, Switzerland: Medicines; 2019:6.
|
[43] |
Sun MY, Song YN, Zhang M, Zhang CY, Zhang LJ, Zhang H. Ginsenoside Rg3 inhibits the migration and invasion of liver cancer cells by increasing the protein expression of ARHGAP9. Oncol Lett. 2019; 17: 965- 973.
|
[44] |
Kim YJ, Choi WI, Jeon BN, et al. Stereospecific effects of ginsenoside 20-Rg3 inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses lung cancer migration, invasion and anoikis resistance. Toxicology. 2014; 322: 23- 33.
|
[45] |
Tian L, Shen D, Li X, et al. Ginsenoside Rg3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4. Oncotarget. 2016; 7: 1619- 1632.
|
[46] |
Cai N, Yang Q, Che DB, Jin X. 20(S)-Ginsenoside Rg3 regulates the Hedgehog signaling pathway to inhibit proliferation and epithelial-mesenchymal transition of lung cancer cells. Pharmazie. 2021; 76: 431- 436.
|
[47] |
Phi LTH, Wijaya YT, Sari IN, et al. 20(R)-Ginsenoside Rg3 influences cancer stem cell properties and the epithelial-mesenchymal transition in colorectal cancer via the SNAIL signaling Axis. OncoTargets Ther. 2019; 12: 10885- 10895.
|
[48] |
Li X, Liu W, Geng C, et al. Ginsenoside Rg3 suppresses epithelial-mesenchymal transition via downregulating notch-hes1 signaling in colon cancer cells. Am J Chin Med. 2021; 49: 217- 235.
|
[49] |
Xu TM, Cui MH, Xin Y, et al. Inhibitory effect of ginsenoside Rg3 on ovarian cancer metastasis. Chin Med J. 2008; 121: 1394- 1397.
|
[50] |
Liu T, Zhao L, Zhang Y, et al. Ginsenoside 20(S)-Rg3 targets HIF-1α to block hypoxia-induced epithelial-mesenchymal transition in ovarian cancer cells. PLoS One. 2014;9, e103887.
|
[51] |
Liu T, Zhao L, Hou H, Ding L, Chen W, Li X. Ginsenoside 20(S)-Rg3 suppresses ovarian cancer migration via hypoxia-inducible factor 1 alpha and nuclear factor-kappa B signals. Tumour Biol: J Int Soc Oncodevelopment Biol Med. 2017;39, 1010428317692225.
|
[52] |
Lu J, Zhou Y, Zheng X, et al. 20(S)-Rg3 upregulates FDFT1 via reducing miR-4425 to inhibit ovarian cancer progression. Arch Biochem Biophys. 2020;693, 108569.
|
[53] |
Song JH, Eum DY, Park SY, et al. Inhibitory effect of ginsenoside Rg3 on cancer stemness and mesenchymal transition in breast cancer via regulation of myeloid-derived suppressor cells. PLoS One. 2020;15, e0240533.
|
[54] |
Nakhjavani M, Smith E, Palethorpe HM, et al. Anti-Cancer Effects of an Optimised Combination of Ginsenoside Rg3 Epimers on Triple Negative Breast Cancer Models. vol.14. Basel, Switzerland: Pharmaceuticals; 2021.
|
[55] |
Lv S, Chen X, Chen Y, et al. Ginsenoside Rg3 induces apoptosis and inhibits proliferation by down-regulating TIGAR in rats with gastric precancerous lesions. BMC Complement Med Therap. 2022; 22: 188.
|
[56] |
Lee SG, Kang YJ, Nam JO. Anti-metastasis effects of ginsenoside Rg3 in B16F10 cells. J Microbiol Biotechnol. 2015; 25: 1997- 2006.
|
[57] |
Kim JH, Bae YC, Lee JW, Choi JS, Bae SH. Effects of ginsenoside Rg3 on apoptosis in A375.S2 melanoma cells. Transl Cancer Res. 2019;8:357–366.
|
[58] |
Wang T, Zhang C, Wang S. Ginsenoside Rg3 inhibits osteosarcoma progression by reducing circ_0003074 expression in a miR-516b-5p/KPNA4-dependent manner. J Orthop Surg Res. 2021; 16: 724.
|
[59] |
Wang D, Wu C, Liu D, et al. Ginsenoside Rg3 inhibits migration and invasion of nasopharyngeal carcinoma cells and suppresses epithelial mesenchymal transition. BioMed Res Int. 2019, 8407683, 2019.
|
[60] |
Oh HM, Cho CK, Son CG. Experimental evidence for the anti-metastatic action of ginsenoside Rg3: a systematic review. Int J Mol Sci. 2022;23.
|
[61] |
Wu W, Zhou Q, Zhao W, et al. Ginsenoside Rg3 inhibition of thyroid cancer metastasis is associated with alternation of actin skeleton. J Med Food. 2018; 21: 849- 857.
|
[62] |
Pan XY, Guo H, Han J, et al. Ginsenoside Rg3 attenuates cell migration via inhibition of aquaporin 1 expression in PC-3M prostate cancer cells. Eur J Pharmacol. 2012; 683: 27- 34.
|
[63] |
Yue PY, Wong DY, Wu PK, et al. The angiosuppressive effects of 20(R)-ginsenoside Rg3. Biochem Pharmacol. 2006; 72: 437- 445.
|
[64] |
Hu S, Zhu Y, Xia X, et al. Ginsenoside Rg3 prolongs survival of the orthotopic hepatocellular carcinoma model by inducing apoptosis and inhibiting angiogenesis. Anal Cell Pathol. 2019, 3815786. Amsterdam) 2019.
|
[65] |
Tang YC, Zhang Y, Zhou J, et al. Ginsenoside Rg3 targets cancer stem cells and tumor angiogenesis to inhibit colorectal cancer progression in vivo. Int J Oncol. 2018; 52: 127- 138.
|
[66] |
Zeng Z, Nian Q, Chen N, et al. Ginsenoside Rg3 inhibits angiogenesis in gastric precancerous lesions through downregulation of Glut1 and Glut4. Biomed pharmacother = Biomed pharmacother. 2022;145, 112086.
|
[67] |
Guo JQ, Zheng QH, Chen H, et al. Ginsenoside Rg3 inhibition of vasculogenic mimicry in pancreatic cancer through downregulation of VE-cadherin/EphA2/MMP9/MMP2 expression. Int J Oncol. 2014; 45: 1065- 1072.
|
[68] |
Wu R, Ru Q, Chen L, Ma B, Li C. Stereospecificity of ginsenoside Rg3 in the promotion of cellular immunity in hepatoma H22-bearing mice. J Food Sci. 2014; 79: H1430- H1435.
|
[69] |
Yang X, Zou J, Cai H, et al. Ginsenoside Rg3 inhibits colorectal tumor growth via down-regulation of C/EBPβ/NF-κB signaling. Biomed pharmacother = Biomed pharmacother. 2017; 96: 1240- 1245.
|
[70] |
Chen C, Wang YS, Zhang ET, et al. Ginsenoside Rh2 exerts its anti-tumor effect by disrupting the HSP90a-cdc37 system in human liver cancer cells. Int J Mol Sci. 2021;22, 20S.
|
[71] |
Chen J, Peng H, Ou-Yang X, He X. Research on the antitumor effect of ginsenoside Rg3 in B16 melanoma cells. Melanoma Res. 2008; 18: 322- 329.
|
[72] |
Park D, Bae DK, Jeon JH, et al. Immunopotentiation and antitumor effects of a ginsenoside Rg3-fortified red ginseng preparation in mice bearing H460 lung cancer cells. Environ Toxicol Pharmacol. 2011; 31: 397- 405.
|
[73] |
Fan H, Xiao-Ling S, Yaliu S, et al. Comparative pharmacokinetics of ginsenoside Rg3 and ginsenoside Rh2 after oral administration of ginsenoside Rg3 in normal and walker 256 tumor-bearing rats. Phcog Mag. 2016; 12: 21- 24.
|
[74] |
Jiang Z, Yang Y, Yang Y, et al. Ginsenoside Rg3 attenuates cisplatin resistance in lung cancer by downregulating PD-L1 and resuming immune. Biomed pharmacother = Biomed pharmacother. 2017; 96: 378- 383.
|
[75] |
Lee YJ, Lee S, Ho JN, et al. Synergistic antitumor effect of ginsenoside Rg3 and cisplatin in cisplatin-resistant bladder tumor cell line. Oncol Rep. 2014; 32: 1803- 1808.
|
[76] |
Wang X, He R, Geng L, Yuan J, Fan H. Ginsenoside Rg3 alleviates cisplatin resistance of gastric cancer cells through inhibiting SOX2 and the PI3K/Akt/mTOR signaling Axis by up-regulating miR-429. Front Genet. 2022;13, 823182.
|
[77] |
Tan Q, Lin S, Zeng Y, et al. Ginsenoside Rg3 attenuates the osimertinib resistance by reducing the stemness of non-small cell lung cancer cells. Environ Toxicol. 2020; 35: 643- 651.
|
[78] |
Kim SM, Lee SY, Yuk DY, et al. Inhibition of NF-kappaB by ginsenoside Rg3 enhances the susceptibility of colon cancer cells to docetaxel. Arch Pharm Res (Seoul). 2009; 32: 755- 765.
|
[79] |
Hong S, Cai W, Huang Z, et al. Ginsenoside Rg3 enhances the anticancer effect of 5- FU in colon cancer cells via the PI3K/AKT pathway. Oncol Rep. 2020; 44: 1333- 1342.
|
[80] |
Kim SM, Lee SY, Cho JS, et al. Combination of ginsenoside Rg3 with docetaxel enhances the susceptibility of prostate cancer cells via inhibition of NF-kappaB. Eur J Pharmacol. 2010; 631: 1- 9.
|
[81] |
Ahmmed B, Kampo S, Khan M, et al. Rg3 inhibits gemcitabine-induced lung cancer cell invasiveness through ROS-dependent, NF-κB- and HIF-1α-mediated downregulation of PTX3. J Cell Physiol. 2019; 234: 10680- 10697.
|
[82] |
Dai Y, Wang W, Sun Q, Tuohayi J. Ginsenoside Rg3 promotes the antitumor activity of gefitinib in lung cancer cell lines. Exp Ther Med. 2019; 17: 953- 959.
|
[83] |
Shan K, Deng Y, Du Z, Yue P, Yang S. Examination of combined treatment of ginsenoside Rg3 and 5-fluorouracil in lung adenocarcinoma cells. Comput Math Methods Med. 2022, 2813142, 2022.
|
[84] |
Kim DG, Jung KH, Lee DG, et al. 20(S)-Ginsenoside Rg3 is a novel inhibitor of autophagy and sensitizes hepatocellular carcinoma to doxorubicin. Oncotarget. 2014; 5: 4438- 4451.
|
[85] |
Jiang JW, Chen XM, Chen XH, Zheng SS. Ginsenoside Rg3 inhibit hepatocellular carcinoma growth via intrinsic apoptotic pathway. World J Gastroenterol. 2011; 17: 3605- 3613.
|
[86] |
Lu M, Fei Z, Zhang G. Synergistic anticancer activity of 20(S)-Ginsenoside Rg3 and Sorafenib in hepatocellular carcinoma by modulating PTEN/Akt signaling pathway. Biomed pharmacother = Biomed pharmacother. 2018; 97: 1282- 1288.
|
[87] |
Wei Q, Ren Y, Zheng X, et al. Ginsenoside Rg3 and sorafenib combination therapy relieves the hepatocellular carcinomaprogression through regulating the HK2-mediated glycolysis and PI3K/Akt signaling pathway. Bioengineered. 2022; 13: 13919- 13928.
|
[88] |
Sun C, Yu Y, Wang L, et al. Additive antiangiogenesis effect of ginsenoside Rg3 with low-dose metronomic temozolomide on rat glioma cells both in vivo and in vitro. J Exp Clin Cancer Res: CR. 2016; 35: 32.
|
[89] |
Chen Z, Wei X, Shen L, Zhu H, Zheng X. 20(S)-ginsenoside-Rg3 reverses temozolomide resistance and restrains epithelial-mesenchymal transition progression in glioblastoma. Cancer Sci. 2019; 110: 389- 400.
|
[90] |
Jiang J, Yuan Z, Sun Y, Bu Y, Li W, Fei Z. Ginsenoside Rg3 enhances the antiproliferative activity of erlotinib in pancreatic cancer cell lines by downregulation of EGFR/PI3K/Akt signaling pathway. Biomed pharmacother = Biomed pharmacother. 2017; 96: 619- 625.
|
[91] |
Yuan Z, Jiang H, Zhu X, Liu X, Li J. Ginsenoside Rg3 promotes cytotoxicity of Paclitaxel through inhibiting NF-κB signaling and regulating Bax/Bcl-2 expression on triple-negative breast cancer. Biomed pharmacother = Biomed pharmacother. 2017; 89: 227- 232.
|
[92] |
Shan K, Wang Y, Hua H, Qin S, Yang A, Shao J. Ginsenoside Rg3 combined with oxaliplatin inhibits the proliferation and promotes apoptosis of hepatocellular carcinoma cells via downregulating PCNA and cyclin D1. Biol Pharm Bull. 2019; 42: 900- 905.
|
[93] |
Wang XJ, Zhou RJ, Zhang N, Jing Z. 20(S)-ginsenoside Rg3 sensitizes human non-small cell lung cancer cells to icotinib through inhibition of autophagy. Eur J Pharmacol. 2019; 850: 141- 149.
|
[94] |
Zhang Q, Kang X, Zhao W. Antiangiogenic effect of low-dose cyclophosphamide combined with ginsenoside Rg3 on Lewis lung carcinoma. Biochem Biophys Res Commun. 2006; 342: 824- 828.
|
[95] |
Liu TG, Huang Y, Cui DD, et al. Inhibitory effect of ginsenoside Rg3 combined with gemcitabine on angiogenesis and growth of lung cancer in mice. BMC Cancer. 2009; 9: 250.
|
[96] |
Xu TM, Xin Y, Cui MH, Jiang X, Gu LP. Inhibitory effect of ginsenoside Rg3 combined with cyclophosphamide on growth and angiogenesis of ovarian cancer. Chin Med J. 2007; 120: 584- 588.
|
[97] |
Zhang Q, Kang X, Yang B, Wang J, Yang F. Antiangiogenic effect of capecitabine combined with ginsenoside Rg3 on breast cancer in mice. Cancer Biother Rad. 2008; 23: 647- 653.
|
[98] |
Zhang Y, Liu QZ, Xing SP, Zhang JL. Inhibiting effect of Endostar combined with ginsenoside Rg3 on breast cancer tumor growth in tumor-bearing mice. Asian Pac J Tropical Med. 2016; 9: 180- 183.
|
[99] |
Peng Z, Wu WW, Yi P. The efficacy of ginsenoside Rg3 combined with first-line chemotherapy in the treatment of advanced non-small cell lung cancer in China: a systematic review and meta-analysis of randomized clinical trials. Front Pharmacol. 2020;11, 630825.
|
[100] |
Wang J, Tian L, Khan MN, et al. Ginsenoside Rg3 sensitizes hypoxic lung cancer cells to cisplatin via blocking of NF-κB mediated epithelial-mesenchymal transition and stemness. Cancer Lett. 2018; 415: 73- 85.
|
[101] |
Park EH, Kim YJ, Yamabe N, et al. Stereospecific anticancer effects of ginsenoside Rg3 epimers isolated from heat-processed American ginseng on human gastric cancer cell. J Ginseng Res. 2014; 38: 22- 27.
|
[102] |
Zhang C, Liu L, Yu Y, Chen B, Tang C, Li X. Antitumor effects of ginsenoside Rg3 on human hepatocellular carcinoma cells. Mol Med Rep. 2012; 5: 1295- 1298.
|
[103] |
Cheong JH, Kim H, Hong MJ, et al. Stereoisomer-specific anticancer activities of ginsenoside Rg3 and Rh2 in HepG2 cells: disparity in cytotoxicity and autophagyinducing effects due to 20(S)-epimers. Biol Pharm Bull. 2015; 38: 102- 108.
|
[104] |
Liu JP, Lu D, Nicholson RC, Li PY, Wang F. Toxicity of a novel anti-tumor agent 20(S)-ginsenoside Rg3: a 26-week intramuscular repeated administration study in Beagle dogs. Food Chem Toxicol: Int J Publ British Ind Biol Res Ass. 2011; 49: 1718- 1727.
|
[105] |
Liu JP, Lu D, Nicholson RC, Zhao WJ, Li PY, Wang F. Toxicity of a novel anti-tumor agent 20(S)-ginsenoside Rg3: a 26-week intramuscular repeated administration study in rats. Food Chem Toxicol: Int J Publ British Ind Biol Res Ass. 2012; 50: 3388- 3396.
|
[106] |
Teng S, Wang Y, Li P, et al. Effects of R type and S type ginsenoside Rg3 on DNA methylation in human hepatocarcinoma cells. Mol Med Rep. 2017; 15: 2029- 2038.
|
[107] |
Luo X, Wang CZ, Chen J, et al. Characterization of gene expression regulated by American ginseng and ginsenoside Rg3 in human colorectal cancer cells. Int J Oncol. 2008; 32: 975- 983.
|
[108] |
Lee SY, Kim GT, Roh SH, et al. Proteomic analysis of the anti-cancer effect of 20S-ginsenoside Rg3 in human colon cancer cell lines. Biosci Biotechnol Biochem. 2009; 73: 811- 816.
|
[109] |
Park JY, Choi P, Lee D, et al. Effect of amino acids on the generation of ginsenoside Rg3 epimers by heat processing and the anticancer activities of epimers in A2780 human ovarian cancer cells. Evid base Compl Alternative Med: eCAM. 2016, 3146402, 2016.
|
[110] |
Zheng X, Zhou Y, Chen W, et al. Ginsenoside 20(S)-Rg3 prevents PKM2-targeting miR-324-5p from H19 sponging to antagonize the warburg effect in ovarian cancer cells. Cell Physiol Biochem: Int J Exp Cell Physiol Biochem Pharmacol. 2018; 51: 1340- 1353.
|
[111] |
Zhao L, Shou H, Chen L, Gao W, Fang C, Zhang P. Effects of ginsenoside Rg3 on epigenetic modification in ovarian cancer cells. Oncol Rep. 2019; 41: 3209- 3218.
|
[112] |
Chen XP, Qian LL, Jiang H, Chen JH. Ginsenoside Rg3 inhibits CXCR4 expression and related migrations in a breast cancer cell line. Int J Clin Oncol. 2011; 16: 519- 523.
|
[113] |
Zou M, Wang J, Gao J, Han H, Fang Y. Phosphoproteomic analysis of the antitumor effects of ginsenoside Rg3 in human breast cancer cells. Oncol Lett. 2018; 15: 2889- 2898.
|
[114] |
Oh J, Yoon HJ, Jang JH, Kim DH, Surh YJ. The standardized Korean Red Ginseng extract and its ingredient ginsenoside Rg3 inhibit manifestation of breast cancer stem cell-like properties through modulation of self-renewal signaling. J Ginseng Res. 2019; 43: 421- 430.
|
[115] |
Kim H, Ji HW, Kim HW, Yun SH, Park JE, Kim SJ. Ginsenoside Rg3 prevents oncogenic long noncoding RNA ATXN8OS from inhibiting tumor-suppressive microRNA-424-5p in breast cancer cells. Biomolecules. 2021;11.
|
[116] |
Aziz F, Wang X, Liu J, Yan Q. Ginsenoside Rg3 induces FUT4-mediated apoptosis in H. pylori CagA-treated gastric cancer cells by regulating SP1 and HSF1 expressions. Toxicol Vitro: Int J Publ Assoc BIBRA. 2016;31:158–166.
|
[117] |
Li B, Qu G. Inhibition of the hypoxia-induced factor-1α and vascular endothelial growth factor expression through ginsenoside Rg3 in human gastric cancer cells. J Cancer Res Therapeut. 2019; 15: 1642- 1646.
|
[118] |
Kim HS, Lee EH, Ko SR, Choi KJ, Park JH, Im DS. Effects of ginsenosides Rg3 and Rh2 on the proliferation of prostate cancer cells. Arch Pharm Res (Seoul). 2004; 27: 429- 435.
|
[119] |
Chen YJ, Wu JY, Deng YY, et al. Ginsenoside Rg3 in combination with artesunate overcomes sorafenib resistance in hepatoma cell and mouse models. J Ginseng Res. 2022; 46: 418- 425.
|
/
〈 | 〉 |