Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

Ginsenoside Rg3: A Review of its Anticancer Mechanisms and Potential Therapeutic Applications

Author(s): Lei Wu, Lin Bai, Wenshu Dai, Yaping Wu, Pengjun Xi, Jie Zhang and Lily Zheng*

Volume 24, Issue 10, 2024

Published on: 04 March, 2024

Page: [869 - 884] Pages: 16

DOI: 10.2174/0115680266283661240226052054

Price: $65

Abstract

Background: Traditional Chinese Medicine (TCM) has a long history of treating various diseases and is increasingly being recognized as a complementary therapy for cancer. A promising natural compound extracted from the Chinese herb ginseng is ginsenoside Rg3, which has demonstrated significant anticancer effects. It has been tested in a variety of cancers and tumors and has proven to be effective in suppressing cancer.

Objectives: This work covers various aspects of the role of ginsenoside Rg3 in cancer treatment, including its biological functions, key pathways, epigenetics, and potential for combination therapies, all of which have been extensively researched and elucidated. The study aims to provide a reference for future research on ginsenoside Rg3 as an anticancer agent and a support for the potential application of ginsenoside Rg3 in cancer treatment.

Graphical Abstract

[1]
Wang, H.; Xu, F.; Wang, X.; Kwon, W.S.; Yang, D.C. Molecular discrimination of Panax ginseng cultivar K-1 using pathogenesis-related protein 5 gene. J. Ginseng Res., 2019, 43(3), 482-487.
[http://dx.doi.org/10.1016/j.jgr.2018.07.001] [PMID: 31308820]
[2]
Mohanan, P.; Subramaniyam, S.; Mathiyalagan, R.; Yang, D.C. Molecular signaling of ginsenosides Rb1, Rg1, and Rg3 and their mode of actions. J. Ginseng Res., 2018, 42(2), 123-132.
[http://dx.doi.org/10.1016/j.jgr.2017.01.008] [PMID: 29719458]
[3]
Zhang, H.; Abid, S.; Ahn, J.C.; Mathiyalagan, R.; Kim, Y.J.; Yang, D.C.; Wang, Y. Characteristics of Panax ginseng cultivars in Korea and China. Molecules, 2020, 25(11), 2635.
[http://dx.doi.org/10.3390/molecules25112635] [PMID: 32517049]
[4]
Kwon, Y.J.; Jang, S.N.; Liu, K.H.; Jung, D.H. Effect of Korean red ginseng on cholesterol metabolites in postmenopausal women with hypercholesterolemia: A pilot randomized controlled trial. Nutrients, 2020, 12(11), 3423.
[http://dx.doi.org/10.3390/nu12113423] [PMID: 33171597]
[5]
Chung, S.I.; Nam, S.J.; Xu, M.; Kang, M.Y.; Lee, S.C. Aged ginseng (Panax ginseng Meyer) reduces blood glucose levels and improves lipid metabolism in high fat diet-fed mice. Food Sci. Biotechnol., 2016, 25(1), 267-273.
[http://dx.doi.org/10.1007/s10068-016-0039-1] [PMID: 30263267]
[6]
Jeon, B.H.; Kim, C.S.; Park, K.S.; Lee, J.W.; Park, J.B.; Kim, K.J.; Kim, S.H.; Chang, S.J.; Nam, K.Y. Effect of Korea red ginseng on the blood pressure in conscious hypertensive rats. Gen. Pharmacol., 2000, 35(3), 135-141.
[http://dx.doi.org/10.1016/S0306-3623(01)00096-9] [PMID: 11744235]
[7]
Baek, K.S.; Yi, Y.S.; Son, Y.J.; Yoo, S.; Sung, N.Y.; Kim, Y.; Hong, S.; Aravinthan, A.; Kim, J.H.; Cho, J.Y. in vitro and in vivo anti-inflammatory activities of Korean Red Ginseng-derived components. J. Ginseng Res., 2016, 40(4), 437-444.
[http://dx.doi.org/10.1016/j.jgr.2016.08.003] [PMID: 27746698]
[8]
Surh, Y.J.; Na, H.K.; Lee, J.Y.; Keum, Y.S. Molecular mechanisms underlying anti-tumor promoting activities of heat-processed panax ginseng C.A. meyer. J. Korean Med. Sci., 2001, 16, S38-S41.
[http://dx.doi.org/10.3346/jkms.2001.16.S.S38] [PMID: 11748375]
[9]
Sun, X.B.; Matsumoto, T.; Yamada, H. Anti-ulcer activity and mode of action of the polysaccharide fraction from the leaves of Panax ginseng. Planta Med., 1992, 58(5), 432-435.
[http://dx.doi.org/10.1055/s-2006-961507] [PMID: 1470667]
[10]
Chung, S.I.; Kang, M.Y.; Lee, S.C. in vitro and in vivo antioxidant activity of aged ginseng (Panax ginseng). Prev. Nutr. Food Sci., 2016, 21(1), 24-30.
[http://dx.doi.org/10.3746/pnf.2016.21.1.24] [PMID: 27069902]
[11]
Fan, W.; Fan, L.; Wang, Z.; Mei, Y.; Liu, L.; Li, L.; Yang, L.; Wang, Z. Rare ginsenosides: A unique perspective of ginseng research. J. Adv. Res., 2024, S2090-1232(24)00003-1.
[http://dx.doi.org/10.1016/j.jare.2024.01.003] [PMID: 38195040]
[12]
Lü, J.M.; Yao, Q.; Chen, C. Ginseng compounds: An update on their molecular mechanisms and medical applications. Curr. Vasc. Pharmacol., 2009, 7(3), 293-302.
[http://dx.doi.org/10.2174/157016109788340767] [PMID: 19601854]
[13]
Shin, B.K.; Kwon, S.W.; Park, J.H. Chemical diversity of ginseng saponins from Panax ginseng. J. Ginseng Res., 2015, 39(4), 287-298.
[http://dx.doi.org/10.1016/j.jgr.2014.12.005] [PMID: 26869820]
[14]
Chopra, P.; Chhillar, H.; Kim, Y.J.; Jo, I.H.; Kim, S.T.; Gupta, R. Phytochemistry of ginsenosides: Recent advancements and emerging roles. Crit. Rev. Food Sci. Nutr., 2023, 63(5), 613-640.
[http://dx.doi.org/10.1080/10408398.2021.1952159] [PMID: 34278879]
[15]
Zhou, P.; Xie, W.; He, S.; Sun, Y.; Meng, X.; Sun, G.; Sun, X. Ginsenoside Rb1 as an anti-diabetic agent and its underlying mechanism analysis. Cells, 2019, 8(3), 204.
[http://dx.doi.org/10.3390/cells8030204] [PMID: 30823412]
[16]
Joh, E.H.; Lee, I.A.; Jung, I.H.; Kim, D.H. Ginsenoside Rb1 and its metabolite compound K inhibit IRAK-1 activation—The key step of inflammation. Biochem. Pharmacol., 2011, 82(3), 278-286.
[http://dx.doi.org/10.1016/j.bcp.2011.05.003] [PMID: 21600888]
[17]
Lee, Y.J.; Jin, Y.R.; Lim, W.C.; Park, W.K.; Cho, J.Y.; Jang, S.; Lee, S.K. Ginsenoside-Rb1 acts as a weak phytoestrogen in MCF-7 human breast cancer cells. Arch. Pharm. Res., 2003, 26(1), 58-63.
[http://dx.doi.org/10.1007/BF03179933] [PMID: 12568360]
[18]
Lee, D.G.; Jang, S.I.; Kim, Y.R.; Yang, K.E.; Yoon, S.J.; Lee, Z.W.; An, H.J.; Jang, I.S.; Choi, J.S.; Yoo, H.S. Anti-proliferative effects of ginsenosides extracted from mountain ginseng on lung cancer. Chin. J. Integr. Med., 2016, 22(5), 344-352.
[http://dx.doi.org/10.1007/s11655-014-1789-8] [PMID: 25159864]
[19]
Li, Y.; He, F.; Zhang, Y.; Pan, Z. Apatinib and ginsenoside-Rb1 synergetically control the growth of hypopharyngeal carcinoma cells. Dis. Markers, 2022, 2022, 1-14.
[http://dx.doi.org/10.1155/2022/3833489] [PMID: 35069931]
[20]
Zhang, J.; Wang, J.; Wu, X.; Wei, Y. Ginsenoside Rb1 inhibits proliferation and promotes apoptosis by regulating HMGB1 in uterine fibroid cells. Artif. Cells Nanomed. Biotechnol., 2019, 47(1), 2967-2971.
[http://dx.doi.org/10.1080/21691401.2019.1643732] [PMID: 31313594]
[21]
Qian, Y.; Huang, R.; Li, S.; Xie, R.; Qian, B.; Zhang, Z.; Li, L.; Wang, B.; Tian, C.; Yang, J.; Xiang, M. Ginsenoside Rh2 reverses cyclophosphamide-induced immune deficiency by regulating fatty acid metabolism. J. Leukoc. Biol., 2019, 106(5), 1089-1100.
[http://dx.doi.org/10.1002/JLB.2A0419-117R] [PMID: 31211478]
[22]
Chen, Y.H.; Lin, Y.N.; Chen, W.C.; Hsieh, W.T.; Chen, H.Y. Treatment of stress urinary incontinence by ginsenoside Rh2. Am. J. Chin. Med., 2014, 42(4), 817-831.
[http://dx.doi.org/10.1142/S0192415X14500529] [PMID: 25004877]
[23]
Lu, C.; Wang, Y.; Lv, J.; Jiang, N.; Fan, B.; Qu, L.; Li, Y.; Chen, S.; Wang, F.; Liu, X. Ginsenoside Rh2 reverses sleep deprivation-induced cognitive deficit in mice. Behav. Brain Res., 2018, 349, 109-115.
[http://dx.doi.org/10.1016/j.bbr.2018.03.005] [PMID: 29544964]
[24]
Park, E.K.; Choo, M.K.; Kim, E.J.; Han, M.J.; Kim, D.H. Antiallergic activity of ginsenoside Rh2. Biol. Pharm. Bull., 2003, 26(11), 1581-1584.
[http://dx.doi.org/10.1248/bpb.26.1581] [PMID: 14600405]
[25]
Tang, X.P.; Tang, G-D.; Fang, C-Y.; Liang, Z-H.; Zhang, L.Y. Effects of ginsenoside Rh2 on growth and migration of pancreatic cancer cells. World J. Gastroenterol., 2013, 19(10), 1582-1592.
[http://dx.doi.org/10.3748/wjg.v19.i10.1582] [PMID: 23538603]
[26]
Cheng, C.C.; Yang, S.M.; Huang, C.Y.; Chen, J.C.; Chang, W.M.; Hsu, S.L. Molecular mechanisms of ginsenoside Rh2-mediated G1 growth arrest and apoptosis in human lung adenocarcinoma A549 cells. Cancer Chemother. Pharmacol., 2005, 55(6), 531-540.
[http://dx.doi.org/10.1007/s00280-004-0919-6] [PMID: 15739095]
[27]
Oh, M.; Choi, Y.H.; Choi, S.; Chung, H.; Kim, K.; Kim, S.I.; Kim, D.K.; Kim, N.D. Anti-proliferating effects of ginsenoside Rh2 on MCF-7 human breast cancer cells. Int. J. Oncol., 1999, 14(5), 869-875.
[http://dx.doi.org/10.3892/ijo.14.5.869] [PMID: 10200336]
[28]
Kim, I.W.; Sun, W.S.; Yun, B.S.; Kim, N.R.; Min, D.; Kim, S.K. Characterizing a full spectrum of physico-chemical properties of (20S)-and (20R)-ginsenoside Rg3 to be proposed as standard reference materials. J. Ginseng Res., 2013, 37(1), 124-134.
[http://dx.doi.org/10.5142/jgr.2013.37.124] [PMID: 23717166]
[29]
Nag, S.A.; Qin, J.J.; Wang, W.; Wang, M.H.; Wang, H.; Zhang, R. Ginsenosides as anticancer agents: in vitro and in vivo activities, structure–activity relationships, and molecular mechanisms of action. Front. Pharmacol., 2012, 3, 25.
[http://dx.doi.org/10.3389/fphar.2012.00025] [PMID: 22403544]
[30]
Tian, J.; Fu, F.; Geng, M.; Jiang, Y.; Yang, J.; Jiang, W.; Wang, C.; Liu, K. Neuroprotective effect of 20(S)-ginsenoside Rg3 on cerebral ischemia in rats. Neurosci. Lett., 2005, 374(2), 92-97.
[http://dx.doi.org/10.1016/j.neulet.2004.10.030] [PMID: 15644271]
[31]
Nakhjavani, M.; Palethorpe, H.M.; Tomita, Y.; Smith, E.; Price, T.J.; Yool, A.J.; Pei, J.V.; Townsend, A.R.; Hardingham, J.E. Stereoselective anti-cancer activities of ginsenoside rg3 on triple negative breast cancer cell models. Pharmaceuticals, 2019, 12(3), 117.
[http://dx.doi.org/10.3390/ph12030117] [PMID: 31374984]
[32]
Bold, R.J.; Termuhlen, P.M.; McConkey, D.J. Apoptosis, cancer and cancer therapy. Surg. Oncol., 1997, 6(3), 133-142.
[http://dx.doi.org/10.1016/S0960-7404(97)00015-7] [PMID: 9576629]
[33]
Debatin, K.M. Apoptosis pathways in cancer and cancer therapy. Cancer Immunol. Immunother., 2004, 53(3), 153-159.
[http://dx.doi.org/10.1007/s00262-003-0474-8] [PMID: 14749900]
[34]
Dong, P.; Zhang, F.; Wu, X.; Hu, Y.; Cao, Y.; Wang, X.; Xiang, S.; Li, M.; Jiang, L.; Tan, Z.; Lu, W.; Weng, H.; Sun, Y.; Gong, W.; Wang, X.; Zhang, Y.; Shi, W.; Gu, J.; Liu, Y.; Li, H. 20(S)-ginsenoside Rg3 promotes senescence and apoptosis in gallbladder cancer cells via the p53 pathway. Drug Des. Devel. Ther., 2015, 9, 3969-3987.
[http://dx.doi.org/10.2147/DDDT.S84527] [PMID: 26309394]
[35]
Wu, K.; Huang, J.; Xu, T.; Ye, Z.; Jin, F.; Li, N.; Lv, B. MicroRNA-181b blocks gensenoside Rg3-mediated tumor suppression of gallbladder carcinoma by promoting autophagy flux via CREBRF/CREB3 pathway. Am. J. Transl. Res., 2019, 11(9), 5776-5787.
[PMID: 31632547]
[36]
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(1), 724.
[http://dx.doi.org/10.1186/s13018-021-02868-7] [PMID: 34930332]
[37]
Park, E.H.; Kim, Y.J.; Yamabe, N.; Park, S.H.; Kim, H.; Jang, H.J.; Kim, J.H.; Cheon, G.J.; Ham, J.; Kang, K.S. Stereospecific anticancer effects of ginsenoside Rg3 epimers isolated from heat-processed American ginseng on human gastric cancer cell. J. Ginseng Res., 2014, 38(1), 22-27.
[http://dx.doi.org/10.1016/j.jgr.2013.11.007] [PMID: 24558306]
[38]
Chung; Quan, H.Y.; Zhang, Y.; Kim, S.H.; Chung, S.H. 20(S)- Ginsenoside Rg3-induced apoptosis in HT-29 colon cancer cells is associated with AMPK signaling pathway. Mol. Med. Rep., 2010, 3(5), 825-831.
[http://dx.doi.org/10.3892/mmr.2010.328] [PMID: 21472321]
[39]
Wang, J.H.; Nao, J.F.; 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., 2014, 35(12), 11985-11994.
[http://dx.doi.org/10.1007/s13277-014-2497-5] [PMID: 25168366]
[40]
Qiu, X.M.; Bai, X.; Jiang, H.F.; He, P.; Wang, J.H. 20-(s)-Ginsenoside Rg3 induces apoptotic cell death in human leukemic U937 and HL-60 cells through PI3K/Akt pathways. Anticancer Drugs, 2014, 25(9), 1072-1080.
[http://dx.doi.org/10.1097/CAD.0000000000000147] [PMID: 25035959]
[41]
Kim, B.M.; Kim, D.H.; Park, J.H.; Na, H.K.; Surh, Y.J. Ginsenoside Rg 3 induces apoptosis of human breast cancer (MDA-MB-231) cells. J. Cancer Prev., 2013, 18(2), 177-185.
[http://dx.doi.org/10.15430/JCP.2013.18.2.177] [PMID: 25337544]
[42]
Wang, J.; Tian, L.; Khan, M.N.; Zhang, L.; Chen, Q.; Zhao, Y.; Yan, Q.; Fu, L.; Liu, J. 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.
[http://dx.doi.org/10.1016/j.canlet.2017.11.037] [PMID: 29199005]
[43]
Xie, Q.; Wen, H.; Zhang, Q.; Zhou, W.; Lin, X.; Xie, D.; Liu, Y. Inhibiting PI3K-AKt signaling pathway is involved in antitumor effects of ginsenoside Rg3 in lung cancer cell. Biomed. Pharmacother., 2017, 85, 16-21.
[http://dx.doi.org/10.1016/j.biopha.2016.11.096] [PMID: 27930981]
[44]
Lee, S.Y.; Kim, G.T.; Roh, S.H.; Song, J.S.; Kim, H.J.; Hong, S.S.; Kwon, S.W.; Park, J.H. Proteomic analysis of the anti-cancer effect of 20S-ginsenoside Rg3 in human colon cancer cell lines. Biosci. Biotechnol. Biochem., 2009, 73(4), 811-816.
[http://dx.doi.org/10.1271/bbb.80637] [PMID: 19352032]
[45]
Bian, S.; Zhao, Y.; Li, F.; Lu, S.; Wang, S.; Bai, X.; Liu, M.; Zhao, D.; Wang, J.; Guo, D. 20(S)-ginsenoside Rg3 promotes HeLa cell apoptosis by regulating autophagy. Molecules, 2019, 24(20), 3655.
[http://dx.doi.org/10.3390/molecules24203655] [PMID: 31658733]
[46]
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. in vitro, 2016, 31, 158-166.
[http://dx.doi.org/10.1016/j.tiv.2015.09.025] [PMID: 26427350]
[47]
Brabletz, T.; Kalluri, R.; Nieto, M.A.; Weinberg, R.A. EMT in cancer. Nat. Rev. Cancer, 2018, 18(2), 128-134.
[http://dx.doi.org/10.1038/nrc.2017.118] [PMID: 29326430]
[48]
Phi, L.T.H.; Wijaya, Y.T.; Sari, I.N.; Kim, K.S.; Yang, Y.G.; Lee, M.W.; Kwon, H.Y. 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.
[http://dx.doi.org/10.2147/OTT.S219063] [PMID: 31849492]
[49]
Cai, N.; Yang, Q.; Che, D.B.; 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(9), 431-436.
[http://dx.doi.org/10.1691/ph.2021.1573] [PMID: 34481534]
[50]
Kim, Y.J.; Choi, W.I.; Jeon, B.N.; Choi, K.C.; Kim, K.; Kim, T.J.; Ham, J.; Jang, H.J.; Kang, K.S.; Ko, H. 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.
[http://dx.doi.org/10.1016/j.tox.2014.04.002] [PMID: 24793912]
[51]
Li, J.; Lu, J.; Ye, Z.; Han, X.; Zheng, X.; Hou, H.; Chen, W.; Li, X.; Zhao, L. 20(S)-Rg3 blocked epithelial-mesenchymal transition through DNMT3A/miR-145/FSCN1 in ovarian cancer. Oncotarget, 2017, 8(32), 53375-53386.
[http://dx.doi.org/10.18632/oncotarget.18482] [PMID: 28881818]
[52]
Groth, C.; Hu, X.; Weber, R.; Fleming, V.; Altevogt, P.; Utikal, J.; Umansky, V. Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression. Br. J. Cancer, 2019, 120(1), 16-25.
[http://dx.doi.org/10.1038/s41416-018-0333-1] [PMID: 30413826]
[53]
Umansky, V.; Blattner, C.; Gebhardt, C.; Utikal, J. The role of myeloid-derived suppressor cells (MDSC) in cancer progression. Vaccines, 2016, 4(4), 36.
[http://dx.doi.org/10.3390/vaccines4040036] [PMID: 27827871]
[54]
Song, J.H.; Eum, D.Y.; Park, S.Y.; Jin, Y.H.; Shim, J.W.; Park, S.J.; Kim, M.Y.; Park, S.J.; Heo, K.; Choi, Y.J. 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(10), e0240533.
[http://dx.doi.org/10.1371/journal.pone.0240533] [PMID: 33091036]
[55]
Li, J.; Liu, T.; Zhao, L.; Chen, W.; Hou, H.; Ye, Z.; Li, X. Ginsenoside 20(S)-Rg3 inhibits the Warburg effect through STAT3 pathways in ovarian cancer cells. Int. J. Oncol., 2015, 46(2), 775-781.
[http://dx.doi.org/10.3892/ijo.2014.2767] [PMID: 25405516]
[56]
Lu, J.; Wang, L.; Chen, W.; Wang, Y.; Zhen, S.; Chen, H.; Cheng, J.; Zhou, Y.; Li, X.; Zhao, L. miR-603 targeted hexokinase-2 to inhibit the malignancy of ovarian cancer cells. Arch. Biochem. Biophys., 2019, 661, 1-9.
[http://dx.doi.org/10.1016/j.abb.2018.10.014] [PMID: 30365936]
[57]
Zhou, Y.; Zheng, X.; Lu, J.; Chen, W.; Li, X.; Zhao, L. Ginsenoside 20(S)-Rg3 inhibits the warburg effect via modulating DNMT3A/ MiR-532-3p/HK2 pathway in ovarian cancer cells. Cell. Physiol. Biochem., 2018, 45(6), 2548-2559.
[http://dx.doi.org/10.1159/000488273] [PMID: 29558748]
[58]
Liberti, M.V.; Locasale, J.W. The warburg effect: How does it benefit cancer cells? Trends Biochem. Sci., 2016, 41(3), 211-218.
[http://dx.doi.org/10.1016/j.tibs.2015.12.001] [PMID: 26778478]
[59]
Zhang, Y.; Yang, J. The impact of cellular senescence in cancer therapy: Is it true or not? Acta Pharmacol. Sin., 2011, 32(10), 1199-1207.
[http://dx.doi.org/10.1038/aps.2011.108] [PMID: 21909124]
[60]
Gorgoulis, V.; Adams, P.D.; Alimonti, A.; Bennett, D.C.; Bischof, O.; Bishop, C.; Campisi, J.; Collado, M.; Evangelou, K.; Ferbeyre, G.; Gil, J.; Hara, E.; Krizhanovsky, V.; Jurk, D.; Maier, A.B.; Narita, M.; Niedernhofer, L.; Passos, J.F.; Robbins, P.D.; Schmitt, C.A.; Sedivy, J.; Vougas, K.; von Zglinicki, T.; Zhou, D.; Serrano, M.; Demaria, M. Cellular senescence: Defining a path forward. Cell, 2019, 179(4), 813-827.
[http://dx.doi.org/10.1016/j.cell.2019.10.005] [PMID: 31675495]
[61]
Collado, M.; Blasco, M.A.; Serrano, M. Cellular senescence in cancer and aging. Cell, 2007, 130(2), 223-233.
[http://dx.doi.org/10.1016/j.cell.2007.07.003] [PMID: 17662938]
[62]
Lee, M.; Lee, J.S. Exploiting tumor cell senescence in anticancer therapy. BMB Rep., 2014, 47(2), 51-59.
[http://dx.doi.org/10.5483/BMBRep.2014.47.2.005] [PMID: 24411464]
[63]
Cairney, C.J.; Bilsland, A.E.; Evans, T.R.J.; Roffey, J.; Bennett, D.C.; Narita, M.; Torrance, C.J.; Keith, W.N. Cancer cell senescence: A new frontier in drug development. Drug Discov. Today, 2012, 17(5-6), 269-276.
[http://dx.doi.org/10.1016/j.drudis.2012.01.019] [PMID: 22314100]
[64]
Roninson, I.B. Tumor cell senescence in cancer treatment. Cancer Res., 2003, 63(11), 2705-2715.
[PMID: 12782571]
[65]
Peng, Y.; Zhang, R.; Yang, X.; Zhang, Z.; Kang, N.; Bao, L.; Shen, Y.; Yan, H.; Zheng, F. Ginsenoside Rg3 suppresses the proliferation of prostate cancer cell line PC3 through ROS‑induced cell cycle arrest. Oncol. Lett., 2018, 17(1), 1139-1145.
[http://dx.doi.org/10.3892/ol.2018.9691] [PMID: 30655875]
[66]
Sin, S.; Kim, S.Y.; Kim, S.S. Chronic treatment with ginsenoside Rg3 induces Akt-dependent senescence in human glioma cells. Int. J. Oncol., 2012, 41(5), 1669-1674.
[http://dx.doi.org/10.3892/ijo.2012.1604] [PMID: 22922739]
[67]
Kim, B.M.; Kim, D.H.; Park, J.H.; Surh, Y.J.; Na, H.K. Ginsenoside Rg3 inhibits constitutive activation of NF-κB signaling in human breast cancer (MDA-MB-231) cells: ERK and Akt as potential upstream targets. J. Cancer Prev., 2014, 19(1), 23-30.
[http://dx.doi.org/10.15430/JCP.2014.19.1.23] [PMID: 25337569]
[68]
Torgovnick, A.; Schumacher, B. DNA repair mechanisms in cancer development and therapy. Front. Genet., 2015, 6, 157.
[http://dx.doi.org/10.3389/fgene.2015.00157] [PMID: 25954303]
[69]
Ou, H.L.; Schumacher, B. DNA damage responses and p53 in the aging process. Blood, 2018, 131(5), 488-495.
[http://dx.doi.org/10.1182/blood-2017-07-746396] [PMID: 29141944]
[70]
Liu, T.; Zuo, L.; Guo, D.; Chai, X.; Xu, J.; Cui, Z.; Wang, Z.; Hou, C. Ginsenoside Rg3 regulates DNA damage in non-small cell lung cancer cells by activating VRK1/P53BP1 pathway. Biomed. Pharmacother., 2019, 120, 109483.
[http://dx.doi.org/10.1016/j.biopha.2019.109483] [PMID: 31629252]
[71]
Kastan, M.B.; Bartek, J. Cell-cycle checkpoints and cancer. Nature, 2004, 432(7015), 316-323.
[http://dx.doi.org/10.1038/nature03097] [PMID: 15549093]
[72]
Murray, A.W. Recycling the cell cycle: Cyclins revisited. Cell, 2004, 116(2), 221-234.
[http://dx.doi.org/10.1016/S0092-8674(03)01080-8] [PMID: 14744433]
[73]
Toettcher, J.E.; Loewer, A.; Ostheimer, G.J.; Yaffe, M.B.; Tidor, B.; Lahav, G. Distinct mechanisms act in concert to mediate cell cycle arrest. Proc. Natl. Acad. Sci., 2009, 106(3), 785-790.
[http://dx.doi.org/10.1073/pnas.0806196106] [PMID: 19139404]
[74]
Liang, Y.; Zhang, T.; Jing, S.; Zuo, P.; Li, T.; Wang, Y.; Xing, S.; Zhang, J.; Wei, Z. 20( S )-ginsenoside Rg3 inhibits lung cancer cell proliferation by targeting EGFR-mediated Ras/Raf/MEK/ERK pathway. Am. J. Chin. Med., 2021, 49(3), 753-765.
[http://dx.doi.org/10.1142/S0192415X2150035X] [PMID: 33641655]
[75]
Yun, C.; Lee, S. The roles of autophagy in cancer. Int. J. Mol. Sci., 2018, 19(11), 3466.
[http://dx.doi.org/10.3390/ijms19113466] [PMID: 30400561]
[76]
Pankiv, S.; Clausen, T.H.; Lamark, T.; Brech, A.; Bruun, J.A.; Outzen, H.; Øvervatn, A.; Bjørkøy, G.; Johansen, T. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J. Biol. Chem., 2007, 282(33), 24131-24145.
[http://dx.doi.org/10.1074/jbc.M702824200] [PMID: 17580304]
[77]
Tanida, I.; Ueno, T.; Kominami, E. LC3 and autophagy. Methods Mol. Biol., 2008, 445, 77-88.
[http://dx.doi.org/10.1007/978-1-59745-157-4_4] [PMID: 18425443]
[78]
Kim, D.G.; Jung, K.H.; Lee, D.G.; Yoon, J.H.; Choi, K.S.; Kwon, S.W.; Shen, H.M.; Morgan, M.J.; Hong, S.S.; Kim, Y.S. 20(S)-Ginsenoside Rg3 is a novel inhibitor of autophagy and sensitizes hepatocellular carcinoma to doxorubicin. Oncotarget, 2014, 5(12), 4438-4451.
[http://dx.doi.org/10.18632/oncotarget.2034] [PMID: 24970805]
[79]
Xue, H.; Zhang, J.; Guo, X.; Wang, J.; Li, J.; Gao, X.; Guo, X.; Li, T.; Xu, S.; Zhang, P.; Liu, Q.; Li, G. CREBRF is a potent tumor suppressor of glioblastoma by blocking hypoxia-induced autophagy via the CREB3/ATG5 pathway. Int. J. Oncol., 2016, 49(2), 519-528.
[http://dx.doi.org/10.3892/ijo.2016.3576] [PMID: 27278737]
[80]
Des Guetz, G.; Uzzan, B.; Nicolas, P.; Cucherat, M.; Morere, J-F.; Benamouzig, R.; Breau, J-L.; Perret, G-Y. Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature. Br. J. Cancer, 2006, 94(12), 1823-1832.
[http://dx.doi.org/10.1038/sj.bjc.6603176] [PMID: 16773076]
[81]
Tang, Y.C.; Zhang, Y.; Zhou, J.; Zhi, Q.; Wu, M.Y.; Gong, F.R.; Shen, M.; Liu, L.; Tao, M.; Shen, B.; Gu, D.M.; Yu, J.; Xu, M.D.; Gao, Y.; Li, W. Ginsenoside Rg3 targets cancer stem cells and tumor angiogenesis to inhibit colorectal cancer progression in vivo. Int. J. Oncol., 2017, 52(1), 127-138.
[http://dx.doi.org/10.3892/ijo.2017.4183] [PMID: 29115601]
[82]
Wu, W.; Zhou, Q.; Zhao, W.; Gong, Y.; Su, A.; Liu, F.; Liu, Y.; Li, Z.; Zhu, J. Ginsenoside Rg3 inhibition of thyroid cancer metastasis is associated with alternation of actin skeleton. J. Med. Food, 2018, 21(9), 849-857.
[http://dx.doi.org/10.1089/jmf.2017.4144] [PMID: 30136914]
[83]
Guo, J.Q.; Zheng, Q.H.; Chen, H.; Chen, L.; Xu, J.B.; Chen, M.Y.; Lu, D.; Wang, Z.H.; Tong, H.F.; Lin, S. Ginsenoside Rg3 inhibition of vasculogenic mimicry in pancreatic cancer through downregulation of VE-cadherin/EphA2/MMP9/MMP2 expression. Int. J. Oncol., 2014, 45(3), 1065-1072.
[http://dx.doi.org/10.3892/ijo.2014.2500] [PMID: 24938458]
[84]
Junmin, S.; Hongxiang, L.; Zhen, L.; Chao, Y.; Chaojie, W. Ginsenoside Rg3 inhibits colon cancer cell migration by suppressing nuclear factor kappa B activity. J. Tradit. Chin. Med., 2015, 35(4), 440-444.
[http://dx.doi.org/10.1016/S0254-6272(15)30122-9] [PMID: 26427115]
[85]
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., 2017, 89, 227-232.
[http://dx.doi.org/10.1016/j.biopha.2017.02.038] [PMID: 28231544]
[86]
Aki, D.; Li, Q.; Li, H.; Liu, Y.C.; Lee, J.H. Immune regulation by protein ubiquitination: roles of the E3 ligases VHL and Itch. Protein Cell, 2019, 10(6), 395-404.
[http://dx.doi.org/10.1007/s13238-018-0586-8] [PMID: 30413999]
[87]
Perrotta, S.; Roberti, D.; Bencivenga, D.; Corsetto, P.; O’Brien, K.A.; Caiazza, M.; Stampone, E.; Allison, L.; Fleck, R.A.; Scianguetta, S.; Tartaglione, I.; Robbins, P.A.; Casale, M.; West, J.A.; Franzini-Armstrong, C.; Griffin, J.L.; Rizzo, A.M.; Sinisi, A.A.; Murray, A.J.; Borriello, A.; Formenti, F.; Della Ragione, F. Effects of germline VHL deficiency on growth, metabolism, and mitochondria. N. Engl. J. Med., 2020, 382(9), 835-844.
[http://dx.doi.org/10.1056/NEJMoa1907362] [PMID: 32101665]
[88]
Liu, T.; Zhao, L.; Zhang, Y.; Chen, W.; Liu, D.; Hou, H.; Ding, L.; Li, X. Ginsenoside 20(S)-Rg3 targets HIF-1α to block hypoxia-induced epithelial-mesenchymal transition in ovarian cancer cells. PLoS One, 2014, 9(9), e103887.
[http://dx.doi.org/10.1371/journal.pone.0103887] [PMID: 25197976]
[89]
Wang, L.; Han, X.; Zheng, X.; Zhou, Y.; Hou, H.; Chen, W.; Li, X.; Zhao, L. [Ginsenoside 20(S)-Rg3 upregulates tumor suppressor VHL gene expression by suppressing DNMT3A-mediated promoter methylation in ovarian cancer cells]. Nan Fang Yi Ke Da Xue Xue Bao, 2021, 41(1), 100-106.
[http://dx.doi.org/10.12122/j.issn.1673-4254.2021.01.14] [PMID: 33509760]
[90]
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., 2017, 39(5)
[http://dx.doi.org/10.1177/1010428317692225] [PMID: 28459376]
[91]
Bartel, D.P. MicroRNAs. Cell, 2004, 116(2), 281-297.
[http://dx.doi.org/10.1016/S0092-8674(04)00045-5] [PMID: 14744438]
[92]
Broderick, J.A.; Zamore, P.D. MicroRNA therapeutics. Gene Ther., 2011, 18(12), 1104-1110.
[http://dx.doi.org/10.1038/gt.2011.50] [PMID: 21525952]
[93]
Di Leva, G.; Croce, C.M. miRNA profiling of cancer. Curr. Opin. Genet. Dev., 2013, 23(1), 3-11.
[http://dx.doi.org/10.1016/j.gde.2013.01.004] [PMID: 23465882]
[94]
Reddy, K.B. MicroRNA (miRNA) in cancer. Cancer Cell Int., 2015, 15(1), 38.
[http://dx.doi.org/10.1186/s12935-015-0185-1] [PMID: 25960691]
[95]
Ashrafizadeh, M.; Ahmadi, Z.; Mohammadinejad, R.; Farkhondeh, T.; Samarghandian, S. MicroRNAs mediate the anti-tumor and protective effects of ginsenosides. Nutr. Cancer, 2020, 72(8), 1264-1275.
[http://dx.doi.org/10.1080/01635581.2019.1675722] [PMID: 31608663]
[96]
Teng, S.; Wang, Y.; Li, P.; Liu, J.; Wei, A.; Wang, H.; Meng, X.; Pan, D.; Zhang, X. Effects of R type and S type ginsenoside Rg3 on DNA methylation in human hepatocarcinoma cells. Mol. Med. Rep., 2017, 15(4), 2029-2038.
[http://dx.doi.org/10.3892/mmr.2017.6255] [PMID: 28260016]
[97]
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(6), 3209-3218.
[http://dx.doi.org/10.3892/or.2019.7115] [PMID: 31002353]
[98]
Ham, J.; Lee, S.; Lee, H.; Jeong, D.; Park, S.; Kim, S.J. 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(6), 1333-1355.
[http://dx.doi.org/10.1142/S0192415X18500702] [PMID: 30149757]
[99]
Yang, G.; Lu, X.; Yuan, L. LncRNA: A link between RNA and cancer. Biochim. Biophys. Acta. Gene Regul. Mech., 2014, 1839(11), 1097-1109.
[http://dx.doi.org/10.1016/j.bbagrm.2014.08.012] [PMID: 25159663]
[100]
Zheng, X.; Zhou, Y.; Chen, W.; Chen, L.; Lu, J.; He, F.; Li, X.; Zhao, L. 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., 2018, 51(3), 1340-1353.
[http://dx.doi.org/10.1159/000495552] [PMID: 30481782]
[101]
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(4), 575-582.
[http://dx.doi.org/10.18388/abp.2020_5343] [PMID: 34038042]
[102]
Ham, J.; Jeong, D.; Park, S.; Kim, H.W.; Kim, H.; Kim, S.J. Ginsenoside Rg3 and korean red ginseng extract epigenetically regulate the tumor-related long noncoding RNAs RFX3-AS1 and STXBP5-AS1. J. Ginseng Res., 2019, 43(4), 625-634.
[http://dx.doi.org/10.1016/j.jgr.2019.02.004] [PMID: 31700260]
[103]
Kim, H.; Ji, H.W.; Kim, H.W.; Yun, S.H.; Park, J.E.; Kim, S.J. Ginsenoside Rg3 prevents oncogenic long noncoding RNA ATXN8OS from inhibiting tumor-suppressive microRNA-424-5p in breast cancer cells. Biomolecules, 2021, 11(1), 118.
[http://dx.doi.org/10.3390/biom11010118] [PMID: 33477683]
[104]
Vo, J.N.; Cieslik, M.; Zhang, Y.; Shukla, S.; Xiao, L.; Zhang, Y.; Wu, Y.M.; Dhanasekaran, S.M.; Engelke, C.G.; Cao, X.; Robinson, D.R.; Nesvizhskii, A.I.; Chinnaiyan, A.M. The landscape of circular RNA in cancer. Cell, 2019, 176(4), 869-881.e13.
[http://dx.doi.org/10.1016/j.cell.2018.12.021] [PMID: 30735636]
[105]
Dai, Y.; Wang, W.; Sun, Q.; Tuohayi, J. Ginsenoside Rg3 promotes the antitumor activity of gefitinib in lung cancer cell lines. Exp. Ther. Med., 2018, 17(1), 953-959.
[http://dx.doi.org/10.3892/etm.2018.7001] [PMID: 30651886]
[106]
Kim, S.M.; Lee, S.Y.; Yuk, D.Y.; Moon, D.C.; Choi, S.S.; Kim, Y.; Han, S.B.; Oh, K.W.; Hong, J.T. Inhibition of NF-κB by ginsenoside Rg3 enhances the susceptibility of colon cancer cells to docetaxel. Arch. Pharm. Res., 2009, 32(5), 755-765.
[http://dx.doi.org/10.1007/s12272-009-1515-4] [PMID: 19471891]
[107]
Hong, S.; Cai, W.; Huang, Z.; Wang, Y.; Mi, X.; Huang, Y.; Lin, Z.; Chen, X. Ginsenoside Rg3 enhances the anticancer effect of 5‑FU in colon cancer cells via the PI3K/AKT pathway. Oncol. Rep., 2020, 44(4), 1333-1342.
[http://dx.doi.org/10.3892/or.2020.7728] [PMID: 32945504]
[108]
Liu, T.; Duo, L.; Duan, P. Ginsenoside Rg3 sensitizes colorectal cancer to radiotherapy through downregulation of proliferative and angiogenic biomarkers. Evid. Based Complement. Alternat. Med., 2018, 2018, 1-8.
[http://dx.doi.org/10.1155/2018/1580427] [PMID: 29743919]
[109]
Lee, T.; Lau, T.; Ng, I. Doxorubicin-induced apoptosis and chemosensitivity in hepatoma cell lines. Cancer Chemother. Pharmacol., 2002, 49(1), 78-86.
[http://dx.doi.org/10.1007/s00280-001-0376-4] [PMID: 11855756]
[110]
Lee, J.Y.; Jung, K.H.; Morgan, M.J.; Kang, Y.R.; Lee, H.S.; Koo, G.B.; Hong, S.S.; Kwon, S.W.; Kim, Y.S. Sensitization of TRAIL-induced cell death by 20(S)-ginsenoside Rg3 via CHOP-mediated DR5 upregulation in human hepatocellular carcinoma cells. Mol. Cancer Ther., 2013, 12(3), 274-285.
[http://dx.doi.org/10.1158/1535-7163.MCT-12-0054] [PMID: 23053497]
[111]
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. Radiopharm., 2008, 23(5), 647-654.
[http://dx.doi.org/10.1089/cbr.2008.0532] [PMID: 18999937]
[112]
Jiang, J.; Yuan, Z.; Sun, Y.; Bu, Y.; Li, W.; Fei, Z. Ginsenoside Rg3 enhances the anti-proliferative activity of erlotinib in pancreatic cancer cell lines by downregulation of EGFR/PI3K/Akt signaling pathway. Biomed. Pharmacother., 2017, 96, 619-625.
[http://dx.doi.org/10.1016/j.biopha.2017.10.043] [PMID: 29035827]
[113]
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(1), 389-400.
[http://dx.doi.org/10.1111/cas.13881] [PMID: 30431207]
[114]
Lee, Y.J.; Lee, S.; Ho, J.N.; Byun, S.S.; Hong, S.K.; Lee, S.E.; Lee, E. Synergistic antitumor effect of ginsenoside Rg3 and cisplatin in cisplatin-resistant bladder tumor cell line. Oncol. Rep., 2014, 32(5), 1803-1808.
[http://dx.doi.org/10.3892/or.2014.3452] [PMID: 25175462]
[115]
Kim, S.S.; Seong, S.; Kim, S.Y. Synergistic effect of ginsenoside Rg3 with verapamil on the modulation of multidrug resistance in human acute myeloid leukemia cells. Oncol. Lett., 2014, 7(4), 1265-1269.
[http://dx.doi.org/10.3892/ol.2014.1826] [PMID: 24944704]
[116]
Liu, C.; Gong, Q.; Chen, T.; Lv, J.; Feng, Z.; Liu, P.; Deng, Z. Treatment with 20(S)-ginsenoside Rg3 reverses multidrug resistance in A549/DDP xenograft tumors. Oncol. Lett., 2018, 15(4), 4376-4382.
[http://dx.doi.org/10.3892/ol.2018.7849] [PMID: 29541206]
[117]
Kwok, H.H.; Guo, G.L.; Lau, J.K.C.; Cheng, Y.K.; Wang, J.R.; Jiang, Z.H.; Keung, M.H.; Mak, N.K.; Yue, P.Y.K.; Wong, R.N.S. Stereoisomers ginsenosides-20(S)-Rg3 and -20(R)-Rg3 differentially induce angiogenesis through peroxisome proliferator-activated receptor-gamma. Biochem. Pharmacol., 2012, 83(7), 893-902.
[http://dx.doi.org/10.1016/j.bcp.2011.12.039] [PMID: 22234331]
[118]
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(4), 636-642.
[http://dx.doi.org/10.1016/j.fitote.2012.01.006] [PMID: 22310172]
[119]
Qiu, R.; Qian, F.; Wang, X.; Li, H.; Wang, L. Targeted delivery of 20(S)-ginsenoside Rg3-based polypeptide nanoparticles to treat colon cancer. Biomed. Microdevices, 2019, 21(1), 18.
[http://dx.doi.org/10.1007/s10544-019-0374-0] [PMID: 30783757]
[120]
Yang, R.; Chen, D.; Li, M.; Miao, F.; Liu, P.; Tang, Q. 20(s)-ginsenoside Rg3-loaded magnetic human serum albumin nanospheres applied to HeLa cervical cancer cells in vitro. Biomed. Mater. Eng., 2014, 24(6), 1991-1998.
[http://dx.doi.org/10.3233/BME-141008] [PMID: 25226895]
[121]
Park, J.Y.; Choi, P.; Lee, D.; Kim, T.; Jung, E.B.; Hwang, B.S.; Kang, K.S.; Ham, J. 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. Based Complement. Alternat. Med., 2016, 2016, 1-6.
[http://dx.doi.org/10.1155/2016/3146402] [PMID: 27051448]
[122]
Li, C.; Wang, Z.; Li, G.; Wang, Z.; Yang, J.; Li, Y.; Wang, H.; Jin, H.; Qiao, J.; Wang, H.; Tian, J.; Lee, A.W.; Gao, Y. Acute and repeated dose 26-week oral toxicity study of 20(S)-ginsenoside Rg3 in Kunming mice and Sprague–Dawley rats. J. Ginseng Res., 2020, 44(2), 222-228.
[http://dx.doi.org/10.1016/j.jgr.2018.10.001] [PMID: 32148403]
[123]
Gao, Y.; Wang, G.; Wang, T.; Li, G.; Lin, J.; Sun, L.; Wu, X.; Sun, X.; Wang, H.; Li, C.; Tian, J.; Zhu, J.; Wang, K.; Cho, S. A 26-week 20(S)-ginsenoside Rg3 oral toxicity study in Beagle dogs. Regul. Toxicol. Pharmacol., 2020, 110, 104522.
[http://dx.doi.org/10.1016/j.yrtph.2019.104522] [PMID: 31726191]
[124]
Liu, J.P.; Lu, D.; Nicholson, R.C.; Zhao, W.J.; Li, P.Y.; 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., 2012, 50(10), 3388-3396.
[http://dx.doi.org/10.1016/j.fct.2012.07.004] [PMID: 22819934]
[125]
Liu, J.P.; Lu, D.; Nicholson, R.C.; Li, P.Y.; 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., 2011, 49(8), 1718-1727.
[http://dx.doi.org/10.1016/j.fct.2011.04.017] [PMID: 21540070]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy