Table 1 The major active components, anticancer effects and mechanisms of HCD herbs

Scutellariae Radix

Baicalein, wogonin

Esophageal squamous cell carcinoma (EC-109), glioma (U87MG, U251MG, C6, U251), colon cancer (HCT116), bladder cancer (TSGH8301, BFTC905, RT4, T24, HT1376), breast cancer (T47D, MCF-7, SK-BR-3, MDA-MB-231, SKBR3), leukemia (CEM), pancreatic carcinoma (Colo-357), hepatocellular carcinoma (HepG2, SK-HEP-1), Hodgkin’s lymphoma (L1236), melanoma (SK-MEL-37), nasopharyngeal carcinoma (NPC-TW076, NPC-TW039)

Inhibiting proliferation, invasion, migration and angiogenesis, inducing apoptosis and differentiation

↓MMP2, ↓MMP9, ↑TIMP1, ↑TIMP2, ↓p38, ↑PI3K/AKT, ↓NF-κB, ↑PPAP γ, ↓CDC2-survivin, ↓Wnt, ↓CDK9, ↓HIF-1α, ↓VEGF, ↑GSK3β/β-catenin, ↓ΔNp63, ↑cleaved PARP, ↑caspase-3, ↑caspase-7, ↑p21

[3,4,5,6,7,8,9,10,11, 22, 29]

Coptidis Rhizoma

Berberine

Breast cancer (MCF7, MDA-MB-468), gastric cancer (MKN-74), colon cancer (HCT116, SW480, SW620, DLD-1, KM12, KM12SM, KM12L4A,), esophageal cancer (YES-1, YES-2, YES-3, YES-4, YES-5, YES-6), nasopharyngeal carcinoma (5-8F, C666-1), kidney cancer (G401), bladder cancer (T24), hepatocellular carcinoma (HepG2)

Inhibiting proliferation, invasion, migration and angiogenesis, inducing apoptosis, cell cycle arrest at G0/G1 phase and mitochondrial membrane damage, increasing ROS

↑IFN-β, ↑TNF-α, ↓Cyclin B1, ↓CDC2, ↓Ezrin, ↑p27, ↑p21, ↑Cyclin E, ↑AMPK, ↑WTX, ↓GSK3β/β-catenin, ↓JNK/p38, ↓Wnt, ↓STAT3, ↑caspase-8, ↑caspase-3, ↓Bid, ↑Bax/Bcl-2, ↑Fas, ↑cleaved PARP, ↓NAT, ↓COX-2, ↑TRAIL, ↑VEGF

[13,14,15,16, 19,20,21,22,23,24,25,26,27,28,29,30,31]

Artemisiae annuae Herba

Artemisinin

Leukemia (HL-60, NB4), ovarian cancer (HO-8910), prostate cancer (LNCaP), breast cancer (MCF-7), nasopharyngeal carcinoma (CNE-1, CNE-2), hepatocellular carcinoma (HepG2, SMMC-7721), melanoma (A375P, A375M), myeloma (RPMI 8226), colon cancer (HCT16), cervical cancer (HeLa, Caski)

Inhibiting proliferation, invasion, migration and angiogenesis, Inducing apoptosis, cell cycle arrest at G1 phase and mitochondrial dysfunction, increasing ROS

↑MAPKs, ↓p38MAPK, ↓VEGF, ↓KDR, ↓CDK2, ↓CDK4, ↓cyclin E, ↓cyclin D1, ↓E2F1, ↓BMI-1, ↑RKIP, ↓Bcl-2, ↑Bax, ↑caspase-3, ↓IGF-IR, ↓MMP2, ↓TIMP2, ↓α_Vβ₃, ↓NF-κB

[34,35,36,37,38,39,40,41,42,43]

Hedyotis diffusa

Ursolic acid, methylanthraquinone

Histocytic lymphoma (U937), leukemia (HL-60), colon cancer (HT-29), melanoma (B16-F10), lung cancer (A549), breast cancer (MCF-7), prostate cancer (LNCaP), Tsu-Pr1, MDA-MB-453, DU-145, cervical cancer (C-33A, U14), sarcoma (S180), hepatocellular carcinoma (HepG2, H22, SMMC-7721)

Inhibiting proliferation, migration and angiogenesis, inducing differentiation, apoptosis, cell cycle arrest at G0/G1, S or G2/M phases, DNA fragmentation and mitochondrial dysfunction

↑interferon-γ, ↑TNF-α, ↑IL-1, ↓NF-κB, ↑Fas, ↑p53, ↑p21/Cip1, ↓p27/kip1, ↑caspase-3, ↑caspase-9, ↑AP-1, ↓Bcl-2, ↑Bax, ↓STAT3, ↓cyclin D, ↓cyclin D1, ↓cyclin D2, ↓cyclin E, ↓CDK4, ↓CDK2, ↓E2F1, ↑Fas-L, ↑TRAIL, ↓MAPK/ERK, ↓JNK, ↑PI3K, ↑p21/WAF1, ↑CDKN1A, ↓cyclin A2, ↓cyclin B1, ↓ODC1, ↓VEGF-α, ↑HSP 70, ↑P16, ↓pim-1, ↓rel, ↓ras, ↓fos, ↓myc, ↑IFN-γ

[45,46,47,48,49,50,51, 53]

Rabdosiae rubescentis Herba

Oridonin

Hepatocellular carcinoma (HepG2), gallbladder carcinoma (SGC996, NOZ), breast cancer (MCF-7, MDA-MB-231), cervical cancer (HeLa), histiocytic lymphoma (U937), pancreatic cancer (SW1990)

Inhibiting proliferation, migration and invasion, inducing apoptosis, autophagy, DNA damage and cell cycle arrest at S and G2/M phases, increasing ROS

↑Hsp70-1, ↑STAP, ↑TCTP, ↑Sti1, ↑PPase, ↓hnRNP-1, ↑HP1 β, ↑GlyRS, ↓NF-κB, ↑Bax/Bcl-2, ↑caspase-3, ↑caspase-9, ↑cleaved PARP, ↓IKKα, ↓IKKβ, ↓mTOR, ↑Fas, ↑PPAR-γ, ↓MMP2/MMP9, ↓Integrin β, ↓FAK, ↓Akt, ↓FOXO, ↓GSK3, ↓ERK, ↓IL-1β, ↑Beclin-1, ↑LC3 II/I, ↑Atg4B, ↓p38 MAPK, ↑p53, ↑p21

[53, 56, 57, 59,60,61,62,63,64]

Scutellariae barbatae Herba

Apigenin, luteolin

Hepatocellular carcinoma (MHCC97H), colon cancer (HT-29), leukemia (LM-1, LM-2), cervical cancer (HeLa)

Inhibiting proliferation and invasion, inducing apoptosis, differentiation and cell cycle arrest at G1 phase

↓MMP-2, ↓MMP-9, ↑TIMP-1, ↑TIMP-2, ↑ACTA2, ↑Calponin, ↑p27, ↓Cyclin D1, ↓CDK4, ↑p21, ↑Bax/Bcl-2, ↓STAT3, ↓ERK1/2, ↓p38, ↑Smac, ↑Apaf-1, ↑caspase-9, ↑caspase-3, ↓IGF-1, ↑cytochrome c

[65,66,67,68,69,70]

Bupleuri Radix

Saikosaponin D

Cervical cancer (HeLa), breast cancer (MCF-7), prostate cancer (PC3), lung cancer (H1299, LLC-1, A549), hepatocellular carcinoma (HepG2, Hep3B), gastric adenocarcinoma (MK-1), cervical cancer (HeLa), melanoma (B16F10), leukemia (P-388), oral epidermoid carcinoma (KB)

Inhibiting proliferation, invasion, metastasis, and angiogenesis, inducing apoptosis, autophagic cell death, cell cycle arrest at G1, or G2/M phases

↑ERK1/2, ↑caspase-3, ↑caspase-9, ↑caspase-7, ↑cleaved PARP, ↑AMPK, ↑mTOR, ↑p27, ↓p53, p21/WAF1, ↑Fas/APO-1, ↑mFasL, ↑sFasL, ↑Bax, ↓IKB-α, ↓NF-κB, ↓Bcl-XL, ↓SERCA Ca²⁺ pump, ↑[Ca²⁺]_i, ↓telomerase, ↑tubulin polymerization

[91,92,93]

Sophorae flavescentis Radix

Matrine

Hepatocellular carcinoma (H22, S180, SMMC-7721, HepG2, Hep-7402), breast cancer (MA737, MKN45, SGC-70901, MDA-MB-231), gastric cancer (SGC-7901), melanoma (A375, SK-MEL-2, M21, B16-F10), cervical cancer (HeLa), leukemia (K-562), glioma (C6), lung cancer (A549, NCI-H460), ovarian cancer (SK-OV-3), central nervous system cancer (XF498), pulmonary adenoma (SPC-A-1), esophagus cancer (Eca-109), colon cancer (SW1116, HCT-15), osteosarcoma (UMR-108, MNNG/HOS), pancreatic cancer (PANC-1), leukmia (U937, HL-60), adenoid cystic carcinoma (ACC-M), retinoblastoma (Y79, WERI-RB1, SO-RB50), nasopharynx cancer (TW03)

Inhibiting proliferation, adhesion, invasion, metastasis and angiogenesis, inducing apoptosis, autophagy, differentiation and cell cycle arrest at G0/G1 or G2 phases, modulating immune function

↑Beclin 1, ↑Bax, ↓Bcl-2, ↑caspase-8, ↑caspase-3, ↑caspase-9, ↑AKT, ↓NF-κB, ↓IκBα, ↓p65, ↓ERK1/2, ↓JNK, ↓p38 MAPK, ↓TNFαl, ↓IKB-α, ↓p65, ↓ERK1/2, ↑E2F1, ↓Rb, ↑Apaf-1, ↓MMP-9, ↓MMP-2, ↓AKT, ↓EGF, ↓VEGF, ↓VEGF2, ↓VEGFR1, ↑Fas, ↑FasL, ↑p21, ↑p27, ↓Cyclin D1, ↓Cyclin E, ↓hTERT

[94, 95]

Pulsatillae Radix

Pulsatilla saponin A, D, H

Gastric cancer (MKN-45, MKN-28, AGS), colon cancer (HT-29, LoVo), hepatocellular carcinoma (Huh-7, HepG2)

Inducing DNA damage and apoptosis

↑Caspase-3, ↑cleaved PARP, ↑Bax, ↓c-Met, ↓AKT, ↓mTOR, ↓p70S6K, ↓HIF-1α, ↓VEGF

[96, 97]

Cremastrae pseudobulbus, Pleiones pseudobulbus

Colchicine

Hepatocellular carcinoma (HCC24/KMUH, HCC38/KMUH)

Inhibit proliferation interacting with tubulin

↑AKAP12, ↑TGF-β2, ↑MX1

[98, 99]

Belamcandae Rhizoma

Tectorigenin

Hepatocellular carcinoma (HepG2), lung cancer (LLC), sarcoma (S180), prostate cancer (LNCaP)

Inhibiting the proliferation and angiogenesis, inducing apoptosis, differentiation and mitochondrial dysfunction, increasing ROS

↑Caspase-3, ↑caspase-9, ↓PDEF, ↓PSA, ↓IGF-1, ↑TIMP-3, ↑cytochrome c, ↑[Ca²⁺]_i

[100, 101]