Table 3 Classification of anti-breast cancer effects of ginsenosides based on the basic hallmarks of tumors (2015–2023)
Ginsenoside type | Anti-breast cancer activity | Cell line | In Vivo/In Vitro | Type of tumor hallmarks | Target spot/signaling pathway | Refs. |
|---|---|---|---|---|---|---|
Rg3 | Activation of exogenous death pathway | MDA-MB-231, MDA-MB-453, BT-549 | In Vivo/In Vitro | Resisting cell death | NF-κB p65, Bcl-2, Bax, caspase-3 | [58] |
20(S)-Rg3 | Increase cell radiosensitivity and induce cell apoptosis | MDA-MB-231 | In Vitro | Resisting cell death | Unknown | [59] |
Rg5 | Inducing apoptosis and autophagy death | MCF-7 | In Vivo | Resisting cell death | PI3K/Akt pathway | [60] |
Rg5 | Caspase-dependent apoptosis can be induced by activating external death receptors and internal mitochondrial signaling pathways, and autophagy can be promoted | MCF-7 | In Vitro | Resisting cell death | PI3K/Akt signaling pathway | [61] |
Rk1 | Activation of mitochondrial-mediated endogenous death pathway | MCF-7 | In Vitro | Resisting cell death | PTEN/PI3K/Akt/mTOR signaling pathway | [62] |
Rk1 | Activation of mitochondrial-mediated endogenous death pathway | MDA-MB-231 | In Vitro | Resisting cell death | ROS/PI3K/Akt pathway | [63] |
Rg1 | Increase cell DNA damage and induce cell apoptosis | MDA-MB-231 | In Vitro | Resisting cell death | Akt, ERK, MAPK,ATM, H2AX, Rad51, TP53, BCl2, CDK2, NF-κB, STAT-3, MAPK, iNOS, MMP2, MMP9, TGFB1, VEGFA, EGFR, SOD, Catalase, GPx, GSH XRCC1, p21, TP53, apaf1, Bax, CASP3, CASP9, ROS, mitochondrial membrane potential | [64] |
Rg1 | Promote cell DNA damage, prevent the elevation of oxidative damage markers, restore antioxidant enzymes to near normal levels, inhibit the expression of cell proliferation and survival-related markers, regulate apoptosis markers, and downregulate invasion and angiogenesis markers | MB-MD-231 | In Vitro | Resisting cell death, Tissue Invasion And Metastasis, Sustained Angiogenesis, Deregulating Cellular Energetics | TP53, Bcl-2, CDK2, NF-κB, STAT-3, MAPK, iNOS, MMP2, MMP9, TGFB1, VEGFA, EGFR, SOD, Catalase, GPx, GSH | [65] |
Rh2 | Upregulation of tumor suppressor gene expression, activation of extrinsic death pathway, and induction of apoptosis | MCF-7 | In Vitro | Resisting cell death | caspase-9/p38 MAPK, p53, Bax, Bcl-2、PRAP | [66] |
Rh2 | Activation of the mitochondrial-mediated endogenous death pathway | MCF-7 | In Vitro | Resisting cell death | Mitochondrial pathway | [67] |
Rh4 | Activation of extrinsic death pathways | MCF-7 | In Vivo/In Vitro | Resisting cell death | Bcl-2, Bax, caspase-8, caspase-3, PARP | [68] |
1f | Activation of the mitochondrial-mediated endogenous death pathway | MCF-7 | In Vitro | Resisting cell death | Unknown | [69] |
Rh1 | Induction of apoptosis and autophagic death | MCF-7, HCC1428 | In Vivo/In Vitro | Resisting cell death | ROS/PI3K/Akt pathway | [70] |
Rh1 | Induce mitochondrial dysfunction, activate mitochondria-mediated endogenous and exogenous death pathways | MDA-MB-231, BT549 | In Vivo/In Vitro | Resisting cell death | PERK/eIF2α/ATF4/CHOP pathway, mtROS, caspase-3 | [71] |
Rh1 | Activation of the mitochondrial-mediated endogenous death pathway | MD-MB-231 | In Vitro | Resisting cell death, tissue invasion, and metastasis | STAT3/NF-κB pathway, MMP2, MMP9, ROS, VEGF-A | [72] |
Rg2 | Induction of autophagic cell death | MCF-7 | In Vitro | Resisting cell death | p-p53, p-AMPK, p-ACC, Atg-7, LC3-II, p62 | [75] |
Rg2 | Activation of the mitochondrial-mediated endogenous death pathway | MCF-7 | In Vitro | Resisting cell death | AMPKpathway, mTOR | [76] |
20(S)-PPT | Induction of apoptosis and nonprotective autophagy | MDA-MB-231, SUM-15-PT | In Vivo/In Vitro | Resisting cell death | Akt/mTOR signaling pathway | [77] |
Rb1 | Increase irreversible cell death under short infrared low light | MCF-7, 4T1 | In Vitro | Resisting cell death | Unknown | [78] |
Rb1 | Induction of apoptosis | MCF-7 | In Vitro | Resisting cell death | Unknown | [79] |
Rh2 | Inhibit cell proliferation, promote apoptosis, and cycle arrest | MCF-7, MD-MB-231 | In Vivo/In Vitro | Self-sufficiency in growth signals | ERβ-TNFα pathway | [89] |
Rg1 | Exert estrogen regulation antagonism and inhibit cell proliferation | MCF-7 | In Vivo/In Vitro | Self-sufficiency in growth signals | ER signalosome, EGFR, c-SrcER, cavolin-1 | [90] |
Rg6 | It can change the paclitaxel resistance of cells by changing the chromosomal instability induced by stress hormones or steroid hormones, reduce the mitotic speed of cells, and inhibit cell proliferation | MCF-7, MDA-MB-468 | In Vitro | Self-sufficiency in growth signals, Non-mutational epigenetic reprogramming | γ-tubulin, MTOC, GR, ER-α pathway | [91] |
Rd | Eliminated VEGF-induced sprouting of blood vessels and inhibited the formation of blood vessels, and inhibited cell proliferation | MDA-MB-231 | In Vivo/In Vitro | Sustained angiogenesis | Akt/mTOR/P70S6 pathway | [94] |
Rg3 | Inhibit proliferation, invasion, and angiogenesis, and enhance autophagy | MCF-7 | In Vivo | Sustained angiogenesis, resisting cell death, tissue invasion and metastasis | EGFA, VEGFB, VEGFC, MMP2, MMP9, p62, mTOR, PI3K, Akt, JNK, Beclin-1, LC3-II/LC3-3 I | [95] |
Rg3 | Reduces cell stem-like properties and inhibits proliferation | MDA-MB-231, MCF-7 | In Vitro | Unlocking phenotypic plasticity, tumor promotion inflammation, resisting cell death, tissue invasion, and metastasis | Akt-mediated self-renewal signaling | [101] |
Rg3 | Reduce the level of stemness markers of tumor cells, inhibit proliferation and metastasis, and promote apoptosis | MDA-MB-231, HCC1143 | In Vivo/In Vitro | Unlocking phenotypic plasticity, tissue invasion and metastasis, resisting cell death | Akt/mTOR pathway, CD44, ALDH | [102] |
Rh2 | Inhibit the senescence phenotype and secretion phenotype of normal breast epithelial cells caused by doxorubicin treatment, | MCF-7, MCF-10A | In Vitro | Unlocking phenotypic plasticity, tumor promotion inflammation | NF-κB pathway, ROSj, SIRT 3, SIRT 5, SOD1, SOD2 | [103] |
Panaxatriol | It can change the phenotype of paclitaxel-resistant cells, inhibit the expression of inflammatory factors and stem cell-related genes, inhibit proliferation and invasion, and induce apoptosis | MDA-MB-231 PTX, SUM159-PR | In Vivo/In Vitro | Unlocking phenotypic plasticity, tumor promotion inflammation, resisting cell death, tissue invasion, and metastasis | IRAK1/NF-κB and ERK pathways | [49] |
Rg3 | Regulating promoter methylation of noncoding RNA inhibits cell proliferation and induces apoptosis | MCF-7 | In Vitro | Non-mutational epigenetic reprogramming, resisting cell death, deregulating cellular energetics, tissue invasion and metastasis | lncRNA STXBP5-AS1, lncRNA RFX3-AS1, STXBP5, GRM1, RFX3, SLC1A1 | [113] |
Rg3 | Regulating promoter methylation of noncoding RNA inhibits cell proliferation and induces apoptosis | MCF-7 | In Vitro | Non-mutational epigenetic reprogramming, resisting cell death, deregulating cellular energetics | lnc RNA ATXN8OS, miR-424-5p, EYA1, DACH1, CHRM3 | [114] |
Rh2 | Regulating promoter methylation of noncoding RNA inhibits cell proliferation and induces apoptosis | MCF-7 | In Vitro | Non-mutational epigenetic reprogramming, resisting cell death, deregulating cellular energetics | ACOX2, FAM107A, lncRNA C3orf67-AS1 | [115] |
Rh2 | Regulation of cell noncoding RNA levels inhibits cell proliferation | MCF-7, MDA-MB-231, T47D | In Vitro | Non-mutational epigenetic reprogramming, deregulating cellular energetics | lnc RNA CFAP20DC-AS1, BBX, TNFAIP3 | [116] |
Rg3 | It inhibits tumor cell proliferation and promotes apoptosis by affecting gene methylation levels to affect the expression levels of tumor-associated proteins | MCF-7 | In Vitro | Non-mutational epigenetic reprogramming, resisting cell death, deregulating cellular energetics | cell morphology-related pathway, TRMT1L, PSMC6, NOX4, ST3GAL4, RNLS, KDM5A | [117] |
Rh2 | It inhibits tumor cell proliferation and promotes apoptosis by affecting gene methylation levels to affect the expression levels of tumor-associated proteins | MCF-7 | In Vitro | Non-mutational epigenetic reprogramming, resisting cell death, deregulating cellular energetics, avoiding immune destruction | CASP1, INSL5, OR52A1, CLINT1, ST3GAL4, C1orf198 | [118] |
Rh2 | Regulating m6A methylation levels regulates the transcriptional activity and subcellular localization of oncogenic proteins | MDA-MB-157 , MCF-7 | In Vitro | Non-mutational epigenetic reprogramming, deregulating cellular energetics | KIF26B, m6A RNA, ZC3H13/CBLL1 | [119] |
Rg1 | Promoting mitotic defects in cells leads to delayed mitotic progression to inhibit cell proliferation | MDA-MB-231, MCF-7 | In Vitro | Non-mutational epigenetic reprogramming, deregulating cellular energetics | Haspin, H3T3ph, Aurora B | [120] |
CK | Reduce cellular glutamine utilization levels to inhibit proliferation and trigger apoptosis | MCF-7, BT474, MDA-MB-231, SUM159, HCC 1806 | In Vivo/In Vitro | Deregulating cellular energetics, resisting cell death, deregulating cellular energetics | ATP, GLS1, GSH, ROS | [130] |
Rg3 | Inhibit glucose uptake by binding glucose transporters, reverse the level of immunosuppression in the tumor microenvironment, and reduce the levels of CAFs and collagen in the tumor microenvironment | 4T1 | In Vivo | Deregulating cellular energetics, avoiding immune destruction | Glut1, TGF-β/Smad pathway, CAFs, Collagen level, CD4, CD8, CD86, CD206, CD11b+/Gr-1+, CD4+FoxP3+, CD45 | [131] |
Rh2 | Regulates the mitochondrial apoptotic pathway, inhibits glycolysis, and inhibits mitochondrial respiration | MCF-7 | In Vitro | Deregulating cellular energetics, resisting cell death, deregulating cellular energetics | ROS, ATP, caspase-9, Bax, HK II | [132] |
Rg3 | Reverse drug resistance, rebuild TME, change macrophage phenotype, inhibit the expression of MDSC, AFs, and collagen fibers, improve tumor-associated inflammation, and promote tumor cell apoptosis | MCF-7 | In Vivo/In Vitro | Avoiding immune destruction, Tumor promotion inflammation, resisting cell death | IL-6/STAT3/p-STAT3 pathway, MDSC, macrophages, TAFs, collagen fibers | [147] |
Rg3 | Reverses the level of immunosuppression in the tumor microenvironment and kills tumor cells by binding glucose-specific transporters | 4T1 | In Vivo | Avoiding immune destruction, tissue invasion, and metastasis | STAT3, CCL2, CD4, CD8, CD86, CD206, CD11b+/Gr-1+, CD4+FoxP3+, CD45, NF-κB, Bcl-2, Bax | [148] |
Rg3 | Reduce PD-1 expression of activated T cells and increase cytokine levels to promote T cell recognition and killing of breast cancer cells | MDA-MB-231 , BT-549 | In Vivo/In Vitro | Avoiding immune destruction, resisting cell death | IFN-γ, IL-2, IL-9, IL-10, IL-22, IL-23, PD-1, PD-L1 | [149] |
Rh2 | Improve tumor-associated inflammation, remodel the structure of TME, and reverse the immunosuppressive environment | 4T1 | In Vivo/In Vitro | Avoiding immune destruction, resisting cell death, Tumor promotion inflammation | α-SMA, TAFs, CD31, CD11b+/F4/80+/CD86+, M1 macrophage, M2 macrophage, IL-6, CD4, CD8 | [150] |
Rg3 | Inhibit angiogenesis and cell invasion, enhance autophagy, and inhibit cell proliferation | MCF-7 | In Vitro | Tissue invasion and metastasis, sustained angiogenesis, resisting cell death, deregulating cellular energetics | VEGFA, VEGFB, VEGFC, MMP2, MMP9, p62, mTOR, PI3K, Akt, JNK, Beclin-1, LC3-II/LC3-I | [156] |
Rh2 | Reduce cell invasion-related proteins to inhibit cell invasion | MDA-MB-231, MCF-7 | In Vitro | Tissue invasion and metastasis | Anxa2-K301A, NF-κB, E-cadherin, N-cadherin, Snail1, Twist, Slug, SIP1, MMP-2, MMP-9, Myc | [157] |
Rd | Changing the expression level of non-coding RNA inhibits cell invasion | 4T1 | In Vivo/In Vitro | Tissue invasion and metastasis | microRNA-18a, Smad2 | [158] |
CK | Inhibit cell proliferation and invasion, induce apoptosis | MCF-7 | In Vitro | Tissue invasion and metastasis, resisting cell death | N-cadherin, vimentin, FN, E-cadherin, PI3K/Akt pathway | [159] |
20(S)-PPD | Reducing the expression level of epidermal growth factor inhibits cell proliferation, metastasis, invasion, and metastasis | MDA-MB-231 , SUM159 | In Vivo/In Vitro | Tissue invasion and metastasis, resisting cell death, deregulating cellular energetics | ERK1/2, p38, JNK pathway, EGFR-mediated MAPK pathway | [160] |