Table 1.
Potential MYC modulators from natural products of herbal medicine for cancer treatment.
| Compound | Cancer phenotypes | Experimental models | Modulators involved in cancer treatments | Pharmacological effects | References |
|---|---|---|---|---|---|
| Apigenin | Anaplastic thyroid carcinoma, Malignant neuroblastoma, Colorectal cancer, prostate carcinoma, Pancreatic cancer, Primary effusion lymphoma, Non-small cell lung cancer |
In vitro: FRO, SK-N-DZ, SK-N-BE2, P19, HCT-116, BxPC-3, PANC-1, PEL, H1975; In vitro doses: 0.75-100 μM; In vivo: Transgenic adenocarcinoma of the mouse prostate; In vivo doses: 20-50 μg/d; |
Inhibiting: p-ERK1/2, p-JNK, p21, p27, Bcl2, c-Myc, VEGF, MMP-2, MMP-9, Axin2, cyclin D1, cyclin B1, β-catenin, p-Akt, p-p70, p-4E-BP-1, XIAP, K-Ras, p65, GSK-3β, STAT3, FLIP, Glut1, PKM2, PTBP1, hTERT, HIF-1α Enhancing: p38, p-p53, Bid, Fas, cleaved PARP-1, cleaved caspase-3, SBDP, ICAD, ratio of LC3B II/I, E-cadherin, cytochrome C |
Inducing caspase-dependent apoptosis, suppressing cancer cell migration, arresting cell cycle, blocking glycolysis of cancer cells | [487-490, 492-494] |
| Artemisinin | Esophageal cancer, Breast cancer, Clear cell renal cell carcinoma |
In vitro: EC109, MDA-MB-231, UMRC-2, CAKI-2, 4T1; In vitro doses: 1-100 μM; In vivo: UMRC-2 tumor-bearing mice; 4T1 tumor-bearing mice; In vivo doses: 20-100 mg/kg |
Inhibiting: β-catenin, c-Myc, Bcl-2, cyclin D1, PCNA, N-cadherin, Vimentin, Snail, p-Akt, TGF-β Enhancing: Bax, cleaved-caspase 3, cleaved-caspase 9, p-p38, E-cadherin, T-bet, IFN-γ, TNF-α |
Inducing caspase-dependent apoptosis, suppressing cancer cell migration and metastasis, promoting T cell-mediated anti-tumor immune responses | [495-499] |
| Baicalin | Ovarian cancer, Jurkat T cell acute lymphoblastic leukemia, Burkitt lymphoma, Erythroleukemia, Colon cancer, Triple negative breast cancer, Osteosarcoma, Hepatocellular carcinoma, Melanoma, B-acute lymphoblastic leukemia |
In vitro: OVCAR-3, CP70, IOSE364, HL-60, K562, CA46, HCT116, SW480, MDA-MB-231, HT-29; MG63, SMMC-7721, HepG2, SK-MEL-2, A375; In vitro doses: 1.25-150 μM In vivo: HCT116 tumor-bearing mice, HT-29 tumor-bearing mice, H22 tumor-bearing mice, B16F0 tumor-bearing mice; In vivo doses: 50-100 mg/kg |
Inhibition: VEGF, HIF-1α, c-Myc, NF-κB, hTERT, Bcl-2, p-Akt, p-IκB, p-Rb, MMP-7, PD-L1, p-STAT3, Glut1, Glut3, p-mTOR, p-p70S6K, p-4E-BP1 Enhancing: cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, Bax, Fas, FasL, Notch1, DEPP, p-Raf1, p-ERK, p16, p27, p-ERK, E-cadherin |
Arresting cell cycle progression, inducing apoptosis, suppressing erythroid differentiation, inhibiting cancer cell proliferation, migration, and invasion, enhancing host T cell responses, inducing cell senescence, inhibiting glycolysis | [500-506] |
| Berberine | Colorectal cancer, Liver Cancer, Triple-negative breast cancer, Neuroblastoma, Diffuse large B-cell lymphoma, Non-small cell lung cancer |
In vitro: KM12C, HCT116, Hep3B, BEL-7404, MDA-MB-231, MCF-7, N2a, LY1, LY8, U2932, H157, H460, H1975, H1975, H460; In vitro doses: 12.5-150 μM In vivo: KM12C tumor-bearing mice, CT26 tumor-bearing mice, Hep3B tumor-bearing mice, A20 tumor-bearing mice, Lewis-tumor-bearing mice; In vivo doses: 4-20 mg/kg |
Inhibition: PCNA, β-catenin, Cdc2, c-Myc, RXRα, HIF-1α, SLC1A5, GLS, PSPH, CDK6, DNMT1, CD133, β-Catenin, Sox2, Notch2, Nestin, cyclin D1, cyclin E, Cdk2, Cdk4, Bcl2, Bcl-xl, MMP-2, MMP-9, Vimentin, p-PI3K, p-Akt, Ras-1, Raf-1, p-ERK1/2, CD47, PD-L1, p-STAT3 Enhancing: p-Akt, PIK3CA, MAP2, p21, p27, p53, Bax, Smad, Nectin, Laminin, NCAM, HSP70, E-cadherin |
Inducing cancer cell apoptosis, regulating cancer cell metabolism, inhibiting cancer cell proliferation, suppressing glutamine uptake, restoring macrophage and T cell functions in tumor microenvironment | [507-513] |
| β-elemene | Non-small cell lung cancer, Cervical cancer | In vitro: A549, PC-9, SiHa, HeLa; In vitro doses: 100 ng/ml -70 μg/ml, | Inhibiting: MMP-2, MMP-9, VEGF, cyclin D1, c-Myc, COX-2, Notch1, Bcl-2, β-catenin, TCF7, SOX2, Vimentin Enhancing: PTEN, p15, p53, Bax, E-cadherin |
Inducing cancer cell cycle arrest, inhibiting cancer cell proliferation, inhibiting cancer EMT | [514-516] |
| Curcumin | Gastric cancer, Pancreatic cancer, Triple negative breast cancer |
In vitro: SGC7901, SW1990, MDA-MB-468; In vitro doses: 5-50 μM, In vivo: SW1990 tumor-bearing mice; In vivo doses: 25 mg/kg |
Inhibiting: c-Myc, H19, Bcl-2, N-cadherin, E2F-1 Enhancing: p53, Bax, cleaved caspase-3 |
Inducing cancer cell apoptosis, arresting cancer cell cycle | [518, 520, 522, 524] |
| (-)-Epigallocatechin-3-gallate | Neuroblastoma, Colorectal cancer, Gastric cancer, Oral squamous cell carcinoma, Hepatoblastoma, Breast cancer, Skin cancer |
In vitro: BE(2)-C, HCT116, SW480, AZ521, SSC-4, HepT1, HepT3, HUH6, HepG2, MDA-MB-231, A431, SCC13; In vitro doses: 1-100 μM In vivo: HCT116 tumor-bearing mice |
Inhibiting: EGFR, MMP-2, MMP-9, COX-2, Notch1, c-Myc, Bmi1, EZH2, p68, β-catenin, cyclin D1, cyclin D2, CDK2, CDK4, p-Tyr Enhancing: PXRγ, cleaved-PARP, Fas, SFRP1, HBP1, CK1α |
Limiting tumor cell sphere formation, inducing apoptosis, arresting tumor cell cycle | [525-529] |
| Gallic acid | Breast cancer, Glioblastoma | In vitro: MCF-7, U87MG. In vitro doses: 300-6000 μM; | Inhibiting: p-Akt, p-JNK, Enhancing: p53, Bax, p-p38, cleaved-casp-3 |
Inducing apoptosis, re-sensitizing cancer cells to anti-cancer agents | [530-533] |
| Ginkgetin | Non-small-cell lung cancer | In vitro: A549; In vitro doses:5 μM; In vivo: A549 tumor-bearing mice, In vivo doses:30 mg/kg | Inhibiting: GPX4, SCL7A1, GSH, HO-1, Nrf2 Enhancing: transferrin, glutamate, cystine, ROS, cleaved caspase-3, cleaved caspase-7, cleaved caspase-9, cleaved PARP |
Inducing apoptosis, inducing ferroptosis | [534, 535] |
| Ginsenoside Rh2 | Non-small cell lung cancer, Liver carcinoma, Leukemia | In vitro: A549, H460, HepG2, NCI-H1975, NCI-H1975/OSIR, HCC827, KG-1a; In vitro doses: 10-80 μM | Inhibiting: Bcl-2, ZEB1, N-cadherin, Vimentin, Glut1, PKM2, LDHA, p-STAT3, c-MYC, MMP-3, TCF4, cyclin D1, p65, p50, Annexin A2 Enhancing: Bax, cleaved caspase-3, E-cadherin, HDAC4, cleaved PARP |
Inducing apoptosis and paraptosis, inhibiting tumor cell proliferation and invasion, suppressing tumor glycolysis | [536-541, 579-581] |
| Ginsenoside Rg3 | Non-small cell lung cancer, Pancreatic ductal adenocarcinoma; Osteosarcoma, Colon cancer |
In vitro: A549, H1299, PANC-1, BxPC-3, 143B, MG63, SW480; In vitro doses: 25-200 μM In vivo: Lewis lung carcinoma cells tumor-bearing mice, PANC-1 tumor-bearing mice; In vivo doses: 10-30 mg/kg |
Inhibiting: NF-κB, MMP-9, ZFP91, MMP-2, MMP-7, N-cadherin, Vimentin, ZEB1, Snail, Twist, β-catenin, c-MYC, cyclin D1, COX-2 | Inducing apoptosis, suppressing cancer cell migration | [536-539, 582, 583] |
| Hypericin | Breast cancer | In vitro: A2780, HL-60, cBCRP, MDA-MB-175-VII, DA3, SQ2, In vitro doses: 0.5-40 μg/ml | Inhibiting: Bcl-2, Raf-1, Plk, cyclin A, cyclin B1, cyclin H, p27 Enhancing: MRP1, p53, |
Inducing apoptosis | [542-547] |
| Icaritin | Burkitt lymphoma, Colon cancer, Acute myeloid leukemia, Hepatocellular Carcinoma | In vitro: P3HR-1; Raji, COLO-205, NB4, HL 60, U937, In vitro doses: 1-20 μM; In vivo: Hepa1-6 tumor-bearing mice; In vivo doses: 70 mg/kg | Inhibiting: Bcl-2, c-Myc, PD-L1, p-IκBα, p-IKKα/β, Bcl-2, cyclin D1, cyclin E, p-ERK, p-AKT Enhancing: cleaved caspase-3, cleaved caspase-7, cleaved caspase-8, cleaved caspase-9, cleaved-PARP, Bax, CD3+ T cells, CD8+ T cells, IFN-γ, ROS |
Inducing adaptive immune responses, inducing apoptosis, attenuating inflammatory microenvironment | [533, 548-550, 552-557] |
| Polysaccharides of Acanthopanax senticosus | Liver cancer | In vitro: HepG2, In vitro doses:10-80 mg/L | Inhibiting: c-Myc, Cyclin D1, β-catenin | Inducing cancer cell apoptosis, arresting cancer cell cycle | [566] |
| Polysaccharides of Albuca bracteata | Colon cancer |
In vitro: CT26, In vitro doses:0.05-0.2 mg/ml In vivo: AOM/DSS-induced CAC mice, CT26 tumor-bearing mice; In vivo doses: 0.5-1 mg/ml |
Inhibiting: IFN-γ, IL-6, TNF-α, MDA, p-STAT3, COX-2, Cyclin D1, c-Myc, β-catenin, PCNA, Vimentin, Enhancing: IL-10, GSH, E-cadherin |
Attenuating inflammatory microenvironment, rebalancing microbiota proportions, suppressing cancer cell proliferation | [564, 565] |
| Polysaccharides of Dendrobium huoshanense | Gastric cancer | In vitro: MFC, In vitro doses:0.025-2.5 mg/ml | Inhibiting: c-Myc Enhancing: p53 |
Inducing cancer cell apoptosis | [563] |
| Polysaccharides of Ganoderma lucidum (Ganoderan) | Non-small cell lung cancer |
In vitro WI-38, H510A, A549: In vitro doses:0.25-5 mg/ml In vivo: A549 tumor-bearing mice, In vivo doses: 10-30 mg/kg |
Inhibiting: Ki67, PCNA, N-cadherin, Vimentin, Snail, Bcl-2, Ras, p-MEK1/2, p-ERK1/2, c-Myc Enhancing: E-cadherin, Bax, cleaved caspase-3, cleaved PARP |
Inducing cancer cell apoptosis, suppressing cancer cell proliferation, Inhibiting EMT | [559-561] |
| Polysaccharides of Laminaria Japonica | Non-small cell lung cancer, Liver cancer |
In vitro: A549, NCI-H292, H22; In vitro doses: 5-20 mg/ml In vivo: A549 tumor-bearing mice In vivo doses: 5-20 mg/kg |
Inhibiting: Ki67, PCNA, Bcl-2, VEGF, N-cadherin, β-catenin, TCF4, c-Myc Enhancing: Bax, cleaved-caspase-3, cleaved caspase-9, E-cadherin |
Inducing cancer cell apoptosis, suppressing cancer cell proliferation, inhibiting EMT | [559-561] |
| Polysaccharides of Lycium barbarum | Renal cell carcinoma |
In vitro: Renca, In vitro doses: 200 μg/ml In vivo: Renca tumor-bearing mice, In vivo doses:20 μg/g |
Inhibiting: Bcl-2, Cyclin D1, c-Myc Enhancing: Bax |
Inducing cancer cell apoptosis, enhancing immune responses | [567] |
| Polysaccharides of Ulva prolifera | Non-small cell lung cancer | In vitro: A549, In vitro doses:400 μg/ml | Inhibiting: MMP-9, p-JNK-2, p-JNK-1, p-ERK-1, p-ERK-2, p-p38, c-Myc | Suppressing cancer cell proliferation and invasion | [562] |
| Resveratrol | Breast cancer, Gastric cancer |
In vitro: MDA-MB-231, SGC7901, BCap37; In vitro doses: 6.25-200 μM, In vivo: SGC7901 tumor-bearing mice, BCap37 tumor-bearing mice; In vivo doses: 25-100 mg/kg |
Inhibiting: c-MYC, cyclin D1, cyclin B1, MMP-2, MMP-9, p-Akt, Sox2, Bmi-1, CD44, p21, p-mTOR, p-Akt, β-cantenin, Wnt 3a, Fibronectin, ZO-1, α-SMA, miRNA-17 Enhancing: Bax, MLKL, p62, VDAC1, LC3, Beclin 1, ATG3, ATG5, p-p38, p-ERK, CHOP, BAP31 |
Suppressing tumor stem cell functions, inducing apoptosis, inhibiting tumor cell proliferation and invasion, promoting adaptive immunity | [584-586] |
| Shikonin | Leukemia, Breast cancer |
In vitro: U937, NB4, Namalwa, Raji, MCF-7, T47D, MDA-MB-231; In vitro doses: 0.1-10 μM In vivo: Namalwa tumor-bearing mice; In vivo doses: 4mg/kg |
Inhibiting: c-Myc, p-Akt, p-ERK1/2, YAP1, Glut1, Bcl-2, miRNA-19a, PI3K, p-mTOR, p70, ERα Enhancing: p-SAPK/JNK, cleaved caspase-3, cleaved caspase-9, cleaved PARP, p-P38, p-JNK |
Inducing cancer cell apoptosis, arresting cell cycle, synergizing with anti-cancer drugs | [571-574] |
| Triptolide | Colorectal cancer, Head and neck cancer, Osteosarcoma, T-cell acute lymphoblastic leukaemia, Pancreatic cancer |
In vitro: HCT116, HT29, HK1, FaDu, C666-1, KB, IM-9, MES/SA, MG-63, Jurkat, Molt4; In vitro doses: 5-200 Nm; In vivo: HK1 tumor-bearing mice; P4057 tumor-bearing mice; In vivo doses: 0.1 mg/kg, |
Inhibiting: cyclin A, cyclin C, cyclin D1, cyclin D3, N-Myc, c-Myc, COX-2, TIE2, VEGF, NRF2, SLC7A11, RPB1, P-gp, SOX2, HIF-1α, β-catenin, TCF7, DNMT1, DNMT3a Enhancing: initiation of GSDME, Bax, Bad, Bak1, cleaved caspase-3, cleaved PARP, ratio of LC3 II/I, Beclin1 |
Inhibiting tumor cell invasion, inducing pyroptosis, reversing multiple drug resistance | [575-578] |