Research Progress on Antitumor Activity and Mechanism of Ginsenosides

WANG Yonghong; AI Zhiyi; ZHANG Junshun; HU Yue; LIU Sitong; LIU Yongzhe; WANG Yuhua; NAN Bo

doi:10.13386/j.issn1002-0306.2022030278

Volume 44 Issue 1

Dec. 2022

Turn off MathJax

Article Contents

Abstract

References

Science and Technology of Food Industry > 2023 > 44(1): 485-491. > DOI: 10.13386/j.issn1002-0306.2022030278

WANG Yonghong, AI Zhiyi, ZHANG Junshun, et al. Research Progress on Antitumor Activity and Mechanism of Ginsenosides[J]. Science and Technology of Food Industry, 2023, 44(1): 485−491. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2022030278.

Citation:

PDF (2683 KB)

Research Progress on Antitumor Activity and Mechanism of Ginsenosides

WANG Yonghong^{1, 2,},
AI Zhiyi^{1, 2},
ZHANG Junshun^{1, 2},
HU Yue^{1, 2},
LIU Sitong^{1, 2},
LIU Yongzhe^{1, 2},
WANG Yuhua^{1, 2, ,},
NAN Bo^{1, 2, ,}

1.
College of Food Science and Engineering, Jilin Agricultural University, Changchun 130000, China
2.
Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun 130000, China

More Information

Received Date: March 22, 2022
Available Online: October 24, 2022

Graphical Abstract

Abstract

Abstract

Ginseng is an important food and medicine homologous plant, which has various physiological functions of antitumor, antiinflammatory, antifatigue and improving immunity. Ginsenosides are the most important active components in ginseng, in vivo and in vitro experiments have confirmed that ginsenosides have significant antitumor activity, among which ginsenoside Rg3 has been used as a monomer drug for adjuvant therapy of tumor patients. Studies have shown that the anti-tumor activity of ginsenosides is achieved through different pathways, including inhibiting tumor cell proliferation, inducing tumor cell apoptosis, inhibiting tumor cell invasion and metastasis, blocking tumor angiogenesis, enhancing organism immune system, and resisting oxidation stress, and synergizing with chemotherapy drugs. This article reviews the antitumor action pathways of ginsenosides, provides a theoretical basis for the development of ginseng antitumor functional foods.
- ginseng,
- ginsenosides,
- antitumor,
- mechanism

FullText(HTML)

References (70)

References

[1]	BAEG I H, SO S H. The world ginseng market and the ginseng (Korea)[J]. Journal of Ginseng Research,2013,37(1):1−7. doi: 10.5142/jgr.2013.37.1
[2]	RIAZ M, RAHMAN N U, ZIA-UL-HAQ M, et al. Ginseng: A dietary supplement as immune-modulator in various diseases[J]. Trends in Food Science & Technology,2019,83:12−30.
[3]	FAN J, WANG Y, YOU Y, et al. Fermented ginseng improved alcohol liver injury in association with changes in the gut microbiota of mice[J]. Food & Function,2019,10(9):5566−5573.
[4]	YING Y, ZHANG Y L, MA C J, et al. Neuroprotective effects of ginsenoside Rg1 against hyperphosphorylated tau-induced diabetic retinal neurodegeneration via activation of IRS-1/Akt/GSK3beta signaling[J]. Journal of Agricultural and Food Chemistry,2019,67(30):8348−8360. doi: 10.1021/acs.jafc.9b02954
[5]	CHEN H, YANG H, DENG J, et al. Ginsenoside Rk3 ameliorates obesity-induced colitis by regulating of intestinal flora and the TLR4/NF-kappaB signaling pathway in C57BL/6 mice[J]. Journal of Agricultural and Food Chemistry,2021,69(10):3082−3093. doi: 10.1021/acs.jafc.0c07805
[6]	LIU Y, FAN D. Ginsenoside Rg5 induces G2/M phase arrest, apoptosis and autophagy via regulating ROS-mediated MAPK pathways against human gastric cancer[J]. Biochemical Pharmacology,2019,168:285−304. doi: 10.1016/j.bcp.2019.07.008
[7]	SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics, 2020[J]. CA: A Cancer Journal for Clinicians,2020,70(1):7−30. doi: 10.3322/caac.21590
[8]	BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA:A Cancer Journal for Clinicians,2018,68(6):394−424. doi: 10.3322/caac.21492
[9]	RADY I, MOHAMED H, RADY M, et al. Cancer preventive and therapeutic effects of EGCG, the major polyphenol in green tea[J]. Egyptian Journal of Basic and Applied Sciences,2019,5(1):1−23.
[10]	CUI H, BASHAR M A E, RADY I, et al. Antiproliferative activity, proapoptotic effect, and cell cycle arrest in human cancer cells of some marine natural product extract[J]. Oxidative Medicine and Cellular Longevity,2020,2020:7948705.
[11]	QI L W, WANG C Z, YUAN C S. Isolation and analysis of ginseng: Advances and challenges[J]. Natural Product Reports,2011,28(3):467−95. doi: 10.1039/c0np00057d
[12]	DENG S, WONG C K C, LAI H C, et al. Ginsenoside-Rb1 targets chemotherapy-resistant ovarian cancer stem cells via simultaneous inhibition of Wnt/beta-catenin signaling and epithelial-to-mesenchymal transition[J]. Oncotarget,2017,8(16):25897−25914. doi: 10.18632/oncotarget.13071
[13]	PHI L T H, WIJAYA Y T, SARI I N, et al. The anti-metastatic effect of ginsenoside Rb2 in colorectal cancer in an EGFR/SOX2-dependent manner[J]. Cancer Medicine,2018,7(11):5621−5631. doi: 10.1002/cam4.1800
[14]	LEE Y J, JIN Y R, LIM W C, et al. Ginsenoside Rc and Re stimulate c-fos expression in MCF-7 human breast carcinoma cells[J]. Archives of Pharmacal Research,2003,26(1):53−7. doi: 10.1007/BF03179932
[15]	TIAN Y Z, LIU Y P, TIAN S C, et al. Antitumor activity of ginsenoside Rd in gastric cancer via up-regulation of Caspase-3 and Caspase-9[J]. Pharmazie,2020,75(4):147−150.
[16]	LI Y, LU J, BAI F, et al. Ginsenoside Rg3 suppresses proliferation and induces apoptosis in human osteosarcoma[J]. Bio Med Research International,2018,2018:4306579.
[17]	CUI Y, SU Y, DENG L, et al. Ginsenoside-Rg5 inhibits retinoblastoma proliferation and induces apoptosis through suppressing Bcl-2 expression[J]. Chemotherapy,2018,63(5):293−300. doi: 10.1159/000495575
[18]	CHEN F, ZHENG S L, HU J N, et al. Octyl ester of ginsenoside Rh2 induces apoptosis and G1 cell cycle arrest in human HepG2 cells by activating the extrinsic apoptotic pathway and modulating the Akt/p38 MAPK signaling pathway[J]. Journal of Agricultural and Food Chemistry,2016,64(40):7520−7529. doi: 10.1021/acs.jafc.6b03519
[19]	HONG Y, FAN D. Ginsenoside Rk1 induces cell death through ROS-mediated PTEN/PI3K/Akt/mTOR signaling pathway in MCF-7 cells[J]. Journal of Functional Foods,2019,57:255−265. doi: 10.1016/j.jff.2019.04.019
[20]	ZHANG X, ZHANG S, SUN Q, et al. Compound K induces endoplasmic reticulum stress and apoptosis in human liver cancer cells by regulating STAT3[J]. Molecules,2018,23(6):1482. doi: 10.3390/molecules23061482
[21]	MAI T T, MOON J, SONG Y, et al. Ginsenoside F2 induces apoptosis accompanied by protective autophagy in breast cancer stem cells[J]. Cancer Letters,2012,321(2):144−153. doi: 10.1016/j.canlet.2012.01.045
[22]	TANG X P, TANG G D, FANG C Y, et al. Effects of ginsenoside Rh2 on growth and migration of pancreatic cancer cells[J]. World Journal of Gastrointestinal Oncology,2013,19(10):1582−1592.
[23]	WANG M, YAN S J, ZHANG H T, et al. Ginsenoside Rh2 enhances the antitumor immunological response of a melanoma mice model[J]. Oncology Letters,2017,13(2):681−685. doi: 10.3892/ol.2016.5490
[24]	JIANG J, YUAN Z, SUN Y, et al. Ginsenoside Rg3 enhances the anti-proliferative activity of erlotinib in pancreatic cancer cell lines by downregulation of EGFR/PI3K/Akt signaling pathway[J]. Biomedicine & Pharmacotherapy,2017,96:619−625.
[25]	MENG L, JI R, DONG X, et al. Antitumor activity of ginsenoside Rg3 in melanoma through downregulation of the ERK and Akt pathways[J]. International Journal of Oncology,2019,54(6):2069−2079.
[26]	XU Y, PENG W, HAN D, et al. Combined treatment of non-small-cell lung cancer using shenyi capsule and platinum-based chemotherapy: A meta-analysis and systematic review[J]. Evidence-Based Complementary and Alternative Medicine,2020,2020:3957193.
[27]	PAN L, ZHANG T, SUN H, et al. Ginsenoside Rg3 (Shenyi capsule) combined with chemotherapy for digestive system cancer in china: A meta-analysis and systematic review[J]. Evidence-based Complementary and Alternative Medicine,2019,2019:2417418.
[28]	JANG H J, HAN I H, KIM Y J, et al. Anticarcinogenic effects of products of heat-processed ginsenoside Re, a major constituent of ginseng berry, on human gastric cancer cells[J]. Journal of Agricultural and Food Chemistry,2014,62(13):2830−2836. doi: 10.1021/jf5000776
[29]	SHANGGUAN W J, LI H, ZHANG Y H. Induction of G2/M phase cell cycle arrest and apoptosis by ginsenoside Rf in human osteosarcoma MG63 cells through the mitochondrial pathway[J]. Oncology Reports,2014,31(1):305−313. doi: 10.3892/or.2013.2815
[30]	WEI L, GUANG Y L. Targeted antitumor activity of ginsenoside (Rg1) in paclitaxelresistant human nasopharyngeal cancer cells are mediated through activation of autophagic cell death, cell apoptosis, endogenous ROS production, S phase cell cycle arrest and inhibition of m-TOR/PI3K/AKT signalling pathway[J]. Journal of Buon,2019,24(5):2056−2061.
[31]	HUYNH D T N, JIN Y, MYUNG C S, et al. Ginsenoside Rh1 induces MCF-7 cell apoptosis and autophagic cell death through ros-mediated akt signaling[J]. Cancers (Basel),2021,13(8):1892. doi: 10.3390/cancers13081892
[32]	DUAN Z, WEI B, DENG J, et al. The anti-tumor effect of ginsenoside Rh4 in MCF-7 breast cancer cells in vitro and in vivo[J]. Biochemical and Biophysical Research Communications,2018,499(3):482−487. doi: 10.1016/j.bbrc.2018.03.174
[33]	ZHAO X, LIU M, LI D. Oleanolic acid suppresses the proliferation of lung carcinoma cells by miR-122/Cyclin G1/MEF2D axis[J]. Molecular and Cellular Biochemistry,2015,400(1−2):1−7. doi: 10.1007/s11010-014-2228-7
[34]	SHI Y, SONG Q, HU D, et al. Oleanolic acid induced autophagic cell death in hepatocellular carcinoma cells via PI3K/Akt/mTOR and ROS-dependent pathway[J]. The Korean Journal of Physiology & Pharmacology,2016,20(3):237−43.
[35]	ZHENG S W, XIAO S Y, WANG J, et al. Inhibitory effects of Ginsenoside Ro on the growth of B16F10 melanoma via its metabolites[J]. Molecules,2019,24(16):2985. doi: 10.3390/molecules24162985
[36]	LEE K M, YUN J H, LEE D H, et al. Chikusetsusaponin IVa methyl ester induces cell cycle arrest by the inhibition of nuclear translocation of beta-catenin in HCT116 cells[J]. Biochemical and Biophysical Research Communications,2015,459(4):591−596. doi: 10.1016/j.bbrc.2015.02.152
[37]	SONG X, WANG W, ZHANG X, et al. Deglucose chikusetsusaponin IVa isolated from rhizoma panacis majoris induces apoptosis in human HepG2 hepatoma cells[J]. Molecular Medicine Reports,2015,12(4):5494−500. doi: 10.3892/mmr.2015.4035
[38]	CHEN X, WU Q S, MENG F C, et al. Chikusetsusaponin IVa methyl ester induces G1 cell cycle arrest, triggers apoptosis and inhibits migration and invasion in ovarian cancer cells[J]. Phytomedicine,2016,23(13):1555−1565. doi: 10.1016/j.phymed.2016.09.002
[39]	HARASHIMA H, DISSMEYER N, SCHNITTGER A. Cell cycle control across the eukaryotic kingdom[J]. Trends in Cell Biology,2013,23(7):345−56. doi: 10.1016/j.tcb.2013.03.002
[40]	BOWARD B, WU T, DALTON S. Concise review: Control of cell fate through cell cycle and pluripotency networks[J]. Stem Cells,2016,34(6):1427−1436. doi: 10.1002/stem.2345
[41]	WU Q, DENG J, FAN D, et al. Ginsenoside Rh4 induces apoptosis and autophagic cell death through activation of the ROS/JNK/p53 pathway in colorectal cancer cells[J]. Biochemical Pharmacology,2018,148:64−74. doi: 10.1016/j.bcp.2017.12.004
[42]	BRENNAN B T C M A. Pro-inflammatory programmed cell death[J]. Trends in Microbiology,2001,9(3):113−114.
[43]	MINAMI Y, NISHIDA N, KUDO M. Therapeutic response assessment of RFA for HCC: Contrast-enhanced US, CT and MRI[J]. World Journal of Gastrointestinal Oncology,2014,20(15):4160−4166.
[44]	PHI L T H, SARI I N, WIJAYA Y T, et al. Ginsenoside Rd inhibits the metastasis of colorectal cancer via epidermal growth factor receptor signaling axis[J]. Iubmb Life,2019,71(5):601−610. doi: 10.1002/iub.1984
[45]	KIM Y J, CHOI W I, JEON B N, et al. Stereospecific effects of ginsenoside 20-Rg3 inhibits TGF-beta1-induced epithelial-mesenchymal transition and suppresses lung cancer migration, invasion and anoikis resistance[J]. Toxicology,2014,322:23−33. doi: 10.1016/j.tox.2014.04.002
[46]	VISSE R, NAGASE H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: Structure, function, and biochemistry[J]. Circulation Research,2003,92(8):827−839. doi: 10.1161/01.RES.0000070112.80711.3D
[47]	JUNG J S, AHN J H, LE T K, et al. Protopanaxatriol ginsenoside Rh1 inhibits the expression of matrix metalloproteinases and the in vitro invasion/migration of human astroglioma cells[J]. Neurochemistry International,2013,63(2):80−86. doi: 10.1016/j.neuint.2013.05.002
[48]	JIN F, ZHU H, SHI F, et al. A retrospective analysis of safety and efficacy of weekly nab-paclitaxel as second-line chemotherapy in elderly patients with advanced squamous non-small-cell lung carcinoma[J]. Clinical Interventions in Aging,2016,11:167−173.
[49]	LIN W S, LELAND J V, HO C T, et al. Occurrence, bioavailability, anti-inflammatory, and anticancer effects of pterostilbene[J]. Journal of Agricultural and Food Chemistry,2020,68(46):12788−12799. doi: 10.1021/acs.jafc.9b07860
[50]	ZHANG E, SHI H, YANG L, et al. Ginsenoside Rd regulates the Akt/mTOR/p70S6K signaling cascade and suppresses angiogenesis and breast tumor growth[J]. Oncology Reports,2017,38(1):359−367. doi: 10.3892/or.2017.5652
[51]	ZENG D, WANG J, KONG P, et al. Ginsenoside Rg3 inhibits HIF-1alpha and VEGF expression in patient with acute leukemia via inhibiting the activation of PI3K/Akt and ERK1/2 pathways[J]. International Journal of Clinical and Experimental Pathology,2014,7(5):2172−2178.
[52]	LEUNG K W, CHEUNG L W, PON Y L, et al. Ginsenoside Rb1 inhibits tube-like structure formation of endothelial cells by regulating pigment epithelium-derived factor through the oestrogen beta receptor[J]. British Journal of Pharmacology,2007,152(2):207−215. doi: 10.1038/sj.bjp.0707359
[53]	PARKIN J, COHEN B. An overview of the immune system[J]. The Lancet,2001,357(9270):1777−1789. doi: 10.1016/S0140-6736(00)04904-7
[54]	NOGUCHI A, KANEKO T, NAITOH K, et al. Impaired and imbalanced cellular immunological status assessed in advanced cancer patients and restoration of the T cell immune status by adoptive T-cell immunotherapy[J]. International Immunopharmacology,2014,18(1):90−97. doi: 10.1016/j.intimp.2013.11.009
[55]	PARK D, BAE D K, JEON J H, et al. Immunopotentiation and antitumor effects of a ginsenoside Rg(3)-fortified red ginseng preparation in mice bearing H460 lung cancer cells[J]. Environmental Toxicology and Pharmacology,2011,31(3):397−405. doi: 10.1016/j.etap.2011.01.008
[56]	LUNA J I, GROSSENBACHER S K, MURPHY W J, et al. Targeting cancer stem cells with natural killer cell immunotherapy[J]. Expert Opinion on Biological Therapy,2017,17(3):313−324. doi: 10.1080/14712598.2017.1271874
[57]	KWON H J, LEE H, CHOI G E, et al. Ginsenoside F1 promotes cytotoxic activity of nk cells via insulin-like growth factor-1-dependent mechanism[J]. Frontiers in Immunology,2018,9:2785. doi: 10.3389/fimmu.2018.02785
[58]	CONSTANTINIDOU A, ALIFIERIS C, TRAFALIS D T. Targeting programmed cell death-1 (PD-1) and Ligand (PD-L1): A new era in cancer active immunotherapy[J]. Pharmacology & Therapeutics,2019,194:84−106.
[59]	HU M, YANG J, QU L, et al. Ginsenoside Rk1 induces apoptosis and downregulates the expression of PD-L1 by targeting the NF-κB pathway in lung adenocarcinoma[J]. Food & Function,2020,11(1):456−471.
[60]	DE SA JUNIOR P L, CAMARA D A D, PORCACCHIA A S, et al. The roles of ROS in cancer heterogeneity and therapy[J]. Oxidative Medicine and Cellular Longevity,2017,2017:2467940.
[61]	ZHOU P, LU S, LUO Y, et al. Attenuation of TNF-α-induced inflammatory injury in endothelial cells by ginsenoside Rb1 via inhibiting NF-kappaB, JNK and p38 signaling pathways[J]. Frontiers in Pharmacology,2017,8:464. doi: 10.3389/fphar.2017.00464
[62]	LI Q, XIANG Y, CHEN Y, et al. Ginsenoside Rg1 Protects cardiomyocytes against hypoxia/reoxygenation injury via activation of Nrf2/HO-1 signaling and inhibition of JNK[J]. Cellular Physiology and Biochemistry,2017,44(1):21−37. doi: 10.1159/000484578
[63]	LIU J F, YAN X D, QI L S, et al. Ginsenoside Rd attenuates Abeta25-35-induced oxidative stress and apoptosis in primary cultured hippocampal neurons[J]. Chemico-Biological Interactions,2015,239:12−18. doi: 10.1016/j.cbi.2015.06.030
[64]	REBUCCI M, MICHIELS C. Molecular aspects of cancer cell resistance to chemotherapy[J]. Biochemical Pharmacology,2013,85(9):1219−1226. doi: 10.1016/j.bcp.2013.02.017
[65]	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]. Journal of Experimental & Clinical Cancer Research,2016,35:32.
[66]	WANG P, SONG D, WAN D, et al. Ginsenoside panaxatriol reverses TNBC paclitaxel resistance by inhibiting the IRAK1/NF-kappaB and ERK pathways[J]. PeerJ,2020,8:e9281. doi: 10.7717/peerj.9281
[67]	JIN L, XU M, LUO X H, et al. Stephania tetrandra and ginseng-containing chinese herbal formulation NSENL reverses cisplatin resistance in lung cancer xenografts[J]. The American Journal of Chinese Medicine,2017,45(2):385−401. doi: 10.1142/S0192415X17500240
[68]	LIN Y, JIANG D, LI Y, et al. Effect of sun ginseng potentiation on epirubicin and paclitaxel-induced apoptosis in human cervical cancer cells[J]. Journal of Ginseng Research,2015,39(1):22−28. doi: 10.1016/j.jgr.2014.08.001
[69]	ZHU H, HE Y S, MA J, et al. The dual roles of ginsenosides in improving the anti-tumor efficiency of cyclophosphamide in mammary carcinoma mice[J]. Journal of Ethnopharmacology,2021,265:113271. doi: 10.1016/j.jep.2020.113271
[70]	JIANG Z, YANG Y, YANG Y, et al. Ginsenoside Rg3 attenuates cisplatin resistance in lung cancer by downregulating PD-L1 and resuming immune[J]. Biomedicine & Pharmacotherapy,2017,96:378−383.

Supplements (0)

Cited By

Cited by

Periodical cited type(3)

1.	陈家伟，谈婷，丁丽，王星，肖理文. 黄曲霉毒素B_1/呕吐毒素/玉米赤霉烯酮三合一时间分辨荧光定量快速检测卡的样品稀释液优化. 粮食加工. 2025(02): 114-119+131 .
2.	韩冰，贾永梅，李志果，周国华，刘培炼，余彪，张玲玲，薛茗月. 核酸适配体传感器在黄曲霉毒素B1检测中应用研究进展. 分析科学学报. 2022(03): 371-376 .
3.	王哲，陈芳，董丽，胡小松. 表面增强拉曼光谱在食源性致病菌检测中的应用研究进展. 食品研究与开发. 2022(17): 184-193 .