Table 1 Effects of TCM and its active ingredients on preventing and treating CRC
Active ingredients | Herb source | Experiments | Effects | Molecular mechanism | Signal pathways | Refs. | |
|---|---|---|---|---|---|---|---|
In vitro model | In vivo model | ||||||
Wogonin (WOG) | Huang Qin (Scutellaria baicalensis Georgi) | SW48 cells | – | Autophagy ↑, Apoptosis ↑, Block cell cycle | ↑: LC3II, Beclin-1, caspase-3, caspase-8, caspase-9, Bax ↓: Bcl-2, p-PI3K, p-Akt | PI3K/Akt STAT3 | [44] |
Coptisine (COP) | Huang Lian (Coptis chinensis Franch.) | HCT-116 | – | Apoptosis ↑, Block cell cycle | ↑: cleaved caspase-3, cleaved caspase-8 ↓: PI3K,Akt, ERK, CyclinD1, CyclinE, CDK2, CDK4 | PI3K/Akt ERK | [47] |
– | HCT-116 xenograft mice | Tumor growth ↓ | ↓: CEA, CA19-9, CYFRA 21 − 1 | ||||
Emodin (EMD) | Da Huang (Rheum palmatum L.) | HCT-116 | HCT-116 xenograft mice | Cell growth ↓, Adhesion ↓, Migration ↓ | ↓: VEGFR2, PI3K, p-Akt | VEGFR2/PI3K/Akt | [49] |
Triptolide (TP) | Lei Gong Teng (Tripterygium wilfordii Hook. f.) | HT29、SW480 | – | Proliferation ↓ | ↓: p-Akt | Akt | [50] |
Platycodin D (PD) | Jie Geng (Platycodon grandiflorus (Jacq.) A. DC.) | HCT-116、LoVo | HCT-116 and LoVo subcutaneous tumor mice | Proliferation ↓, Migration ↓,Invasion ↓ | ↓: p-PI3K, p-Akt | PI3K/Akt | [54] |
Oridonin (ORI) | Dong Ling Cao (Rabdosia rubescens( Hemsl.) Hara) | LoVo、SW480 | – | Proliferation ↓, Apoptosis ↑ | ↑: HERC5 ↓: AP-1, NF-κB, P38 | NF-κB P38-dependent MAPK | [71] |
– | LoVo、SW480 Colostomy implantation model mice | Tumor growth ↓ | ↓: AP-1, NF-κB, P38 | ||||
Baicalein (BE) | Huang Qin (Scutellaria baicalensis Georgi) | HCT-116 | – | Apoptosis ↑, Migration ↓, Invasion ↓ | ↑: PPARγ ↓: caspase-3, caspase-,, MMP2, MMP, p50, P65, iNOS | NF-κB | [73] |
Berberine (BBR) | Huang Lian (Coptis chinensis Franch.), Huang Bai (Phellodendron chinense Schneid.), Xiao Bo (Berberis silva-taroucana Schneid.) | – | AOM/DSS induced CRC model mice | Proliferation ↓, inflammation ↓, Angiogenesis ↓, Invasion ↓ | ↓: Ki-67, β-catenin, IL-1b, TNF-α, NF-κB, MMP9, Ereg, Muc16 | NF-κB | [74] |
Curcumin | Jiang Huang (Curcuma longa L.) | HCT-116、SW620、HT-29 | HCT-116 orthotopic mice | Proliferation ↓, Invasion ↓, Angiogenesis ↓, Apoptosis ↑ | ↓: NF-κB, COX2, Cyclin D1, c-myc, MMP9, ICAM-1, CXCR4, survivin, Bcl-2, VEGF | NF-κB | [75] |
Ginsenoside Rh1 (Rh1) | Ren Shen (Panax ginseng C.A.Mey.) | SW620 | – | Proliferation ↓, Migration ↓, Invasion ↓ | ↑: TIMP3 ↓: MMP1, MMP3, p-P38/P38, p-ERK1/2/ERK1-2, p-JNK/JNK | MAPK | [94] |
– | SW620 xenograft mice | Tumor growth ↓ | ↓: p-P38/P38, p-ERK1/2/ERK1-2, p-JNK/JNK | ||||
Diterpenoid C | Jiang Huang (Curcuma longa L.) | SW620 | – | Proliferation ↓, Apoptosis ↑ | ↑: caspase-3 ↓: p-ERK, p-JNK, p-p38 MAPK | MAPK | [96] |
Podophyllotoxin (PT) | Gui Jiu (Podophyllum peltatum) | HCT-116 | – | Apoptosis ↑, Block cell cycle | ↑: ROS, GRP78, CHOP, p38 MAPK | p38 MAPK | [100] |
Emodin (EMD) | Da Huang (Rheum palmatum L.) | SW620、SW480 | – | Apoptosis ↑, Migration ↓, Invasion ↓ | ↑: HBP1 ↓: CTNNB1, TCF7L2, cyclin D1, c-Myc, snail, vimentin, MMP-2, MMP-9, p300 | Wnt/β-catenin | [117] |
Ginkgolide C (GGC) | Yin Xing Ye (Ginkgo biloba L.) | HT-29 | – | Proliferation ↓, Apoptosis ↑, Migration ↓, Invasion ↓ | ↓: MMP2, MMP9, Wnt3a, β-catenin, Axin-1,p-GSK3β, β-TrCP, c-myc, cyclin D1, survivin | Wnt/β-catenin | [120] |
Curcumin | Jiang Huang (Curcuma longa L.) | SW620 | – | Proliferation ↓, Apoptosis ↑ | ↑: CDX2 ↓: Wnt3a, c-Myc, survivin, cyclin D1 | CDX2/Wnt/β-catenin | [124] |
8-Gingerol | Sheng Jiang (Zingiber officinale Rosc.) | HCT-116、DLD1 | – | Proliferation ↓, Migration ↓ | ↓: p-EGFR, p-STAT, p-ERK, cyclin DI, c-Myc, MMP2 | EGFR/STAT/ERK | [144] |
Gambogic acid (GA) | Teng Huang (Garcinia hanburyi Hook.f.) | HCT-116、SW480 | – | Growth ↓, EMT ↓ | ↑: N-cadherin, vimentin, fibronectin ↓: Nanog, Oct4,Sox2, ALDH1, CD133, Bmi-1, E-cadherin, p-EGFR, p-ERK, ZFP36 | EGFR/ERK/ZFP36 | [148] |
Norcantharidin (NCTD) | Ban Mao (Mylabris phalerata Pallas) | HCT-116、HT-29 | – | Apoptosis ↑, Block cell cycle | ↓: EGFR, p-EGFR, Her-2, p-hER-2, c-Met, p-c-Met, CyclinD1, Rb, CDK-4 | EGFR | [150] |
Ursolic acid (UA) | Bai Hua She She Cao (Oldenlandia diffusa (willd.) Roxb), Mi Hou Tao (Actinidia chinensis Planch.) | HT-29 | – | Proliferation ↓, Apoptosis ↑ | ↑: caspase-3, caspase-9 ↓: Bcl-2, Bcl-xL, p-EGFR, p-RK1/2, p-p38 MAPK, p-JNK | EGFR/MAPK | [151] |
Icariin | Yin Yang Huo (Epimedium brevicornum Maxim.) | HCT-116 | - | Apoptosis ↑ | ↑: p21, p-p53, Bax ↓: Bcl-2 | p53 | [165] |
Ligustrazine (LZ) | Chuan Xiong (Ligusticum chuanxiong Hort.) | SW480, CT26 | – | Apoptosis ↑, Block cell cycle | ↑: p53, Bax, cleaved caspase-3, cleaved caspase-9, cleaved PARP ↓: Bcl-2 | p53 | [169] |
Scutellarin | Ban Zhi Lian (Scutellaria barbata D. Don) | HCT-116 | – | Apoptosis ↑ | ↑: Bax ↓: Bcl-2, p-p53, p21 | p53 | [170] |
Polysaccharides (GLPs) | Ling Zhi (Ganoderma lucidum (Leyss.ex Fr.) Karst.) | HCT-116 | – | Growth ↓, Apoptosis ↑, Block cell cycle | ↑: p21, Bax | p53 | [173] |
Celastrol | Lei Gong Teng (Tripterygium wilfordii Hook. f.) | HCT-116, SW620 | – | Propagation ↓, Adhesion ↓, Metastasis ↓ | ↓: TGF-β1, TGF-βRI, TGF-βRII, p-Smad2/3, Smad4 | TGF-β/Smad | [186] |
Magnolol | Hou Po (Magnolia officinalis Rehd.et Wils.) | HCT-116 | – | EMT ↓ | ↑: E-cadherin, ZO-1, claudin ↓: N-cadherin, TWIST1, Slug, Snail, p-ERK, p-GSK3β, p-Smad | TGF-β | [190] |
Oxymatrine (OM) | Ku Shen (Sophora flavescens Ait.) | RKO | – | EMT ↓ | ↑: E-cadherin ↓: α-SMA, FN, TGF-β1, PAI-1, Smad2/3/4, p-Smad2, P38 | TGF-β/Smad | [193] |
Salidroside | Hong Jing Tian (Rhodiola rosea L.) | HT-29 | – | Apoptosis ↑, Autophagy ↑ | ↑: LC3-II/LC3-I, Beclin-1 ↓: Bcl-2/Bax, p-PI3K, p-AKT, p-mTOR | PI3K/Akt/mTOR | [219] |
Curcumin | Jiang Huang (Curcuma longa L.) | HCT-116 | – | Proliferation ↓ | ↑: p-Akt ↓: mTOR, Raptor, Rictor | Akt/mTOR | [221] |
Andrographolide | Chuan Xin Lian (Andrographis paniculata (Burm. F.) Nees) | HCT-116 | – | Glycolysis ↓ | ↓: PI3K/p110, p-Akt, p-mTOR, PFK1, GLUT1, HK2 | PI3K/Akt/mTOR | [222] |
Nobiletin | Gan Ju (Citrus reticulata Blanco) | HT-29、SW480 | – | Tumor growth ↓, Immunity ↑ | ↑: Bax, caspase3 ↓: p-Akt, p-mTOR, Bcl-2 | PI3K/Akt/mTOR | [225] |
Toosendanin (TSN) | Chuan Lian Zi (MeLia toosendan Sieb.et Zucc.) | HT-29 | HT-29 xenograft nude mice | Proliferation ↓ | ↓: SHH, GLI1, SMO | Hedgehog | [249] |
Berberine (BBR) | Huang Lian (Coptis chinensis Franch.), Huang Bai (Phellodendron chinense Schneid.), Xiao Bo (Berberis silva-taroucana Schneid.) | HT-29 | – | Proliferation ↓, Migration ↓, Invasion ↓, Apoptosis ↑ | ↑: SUFU ↓: SHH, Pthc1, Gli1, SMO, c-Myc | Hedgehog | [250] |
Andrographolide | Chuan Xin Lian (Andrographis paniculata (Burm. F.) Nees) | HCT-116 | – | Proliferation ↓, Migration ↓, Invasion ↓, Apoptosis ↑, Block cell cycle | ↓: CDK2, CyclinB1, Cli1, SMO | Hedgehog | [251] |
Ganoderma atrum polysaccharide (PSG-1) | Ling Zhi (Ganoderma lucidum (Leyss.ex Fr.) Karst.) | – | CT26 bearing mice | Tumor growth ↓, Immunity ↑ | ↑: NO, TNF-α, IL-1β, NF-κB, TLR4, p-p38 ↓: IκBα | TLR4-dependent P38 MAPK | [264] |