From: Anti-malarial drug: the emerging role of artemisinin and its derivatives in liver disease treatment
Hepatic disease | Cell lines | Drug | Dosage | Variations | Refs. |
---|---|---|---|---|---|
Effects on cell cycle | |||||
HCC | HepG2 cells, PLC/PRF/5 cells, Hep3B cells | DHA | 20–40 μM | ↓cyclin B, CDC25C; ↑P21, G2/M phase | [50] |
HepG2 cells, Hep3B cells | ART, DHA | 0–50 μM | ↓E2F1, CDK2 , CDK3, cyclin D1, cyclin E; ↑G1 phase, Kip1/p27, Cip/p21 | [51] | |
Liver fibrosis | HSCs | DHA | 15–50 μM | ↓cyclin A, CDK2; ↑S phase, p53, p21 | [52] |
Effects on cell proliferation | |||||
HCC | HepG2215 cells | DHA | 50–200 μM | ↓cell proliferation | [55] |
HepG2215 cells | DHA | 5–20 μM | ↓cell proliferation, colony formation | [56] | |
HepG2 cells | DHA | 0–200 μM ol/L | ↓cell proliferation; ↑ROS, [Ca2+] | [58] | |
HCCLM6 cells | DHA | 1–100 μM | ↓cell proliferation, E2F1, BCL, PCNA, MKI67, CCNE2 | [59] | |
HCCLM3 cells, MHCC97H cells | ART | 0–100 μM | ↓cell growth, colony formation; cell cycle arrest | [60] | |
CCA | HUCCT-1 cells, FRH201 cells | DHA | 20 μM ol/L | ↓cell proliferation | [57] |
Liver fibrosis | HSCs | ART | 125–225 μM ol/L | ↓cell proliferation | [63] |
LX-2 cells | ART | 0–50 ug/ml | ↓cell proliferation | [64] | |
Effects on cell apoptosis | |||||
Liver fibrosis | LX-2 cells | ART | 12.5–50 ug/ml | ↓Bcl-2; ↑Bax/Bcl-2 | [64] |
HSCs | ART | 150–200 μM ol/L | ↑p53 | [63] | |
HCC | SMMC-7721 cells | Artemisinin | 100–200 μM ol/L | ↑apoptotic rate | [65] |
HepG2 cells | ART and DHA | 0–50 μM | ↓Bcl-2, PARP; ↑Bax, caspase-3, p53, MDM2 | [51] | |
HepG2 cells | ART | 0.5–8 mg/L | ↓p-STAT3; ↑Fas | [69] | |
HepG2, cells | DHA | 0–200 μM ol/L | ↓Bcl-2; ↑GADD153, Bax, | [58] | |
HepG2 cells | DHA | 0–100 μM | ↑cleaved PARP, caspase-3 | [71] | |
SK-Hep-1 cells | DHA | 20–60 μM | ↓PARP, Sp1; ↑caspase8, caspase9, caspase3 | [72] | |
HepG2 and Huh-7 cells | DHA | 0–150 μM | ↓ΔΨm, Mcl-1; ↑Bim, cytochrome c, caspase8, caspase9,caspase3, ROS, Bak | [73] | |
Hep3B and Huh-7 cells | ART | 10–150 μM | ↑ROS, Bax, MOMP, cytochrome c, caspase 9, caspase3 | [74] | |
HepG2 cells | ART | 10–150 μM | ↓ΔΨm, Bcl-2/Bcl-xl; ↑Bax, caspase8, ROS, caspase9, caspase3 | [75] | |
HuH-7 cells and PLC/PRF/5 cells | ART | 1–300 μM | ↓Bcl-2; ↑Bax, caspase-3/7, cleaved PARP1 | [76] | |
CCA | QBC939 cells, HUCCT-1 and FRH201 cells | DHA | 20 μM ol/L | ↑Mcl-1S, Mcl-1S/Mcl-1L, apoptotic rate | |
Effects on angiogenesis, invasion, metastasis | |||||
HCC | SK‐HEP1, SM7721, HepG2, and Huh7 cells | ART | 100 μM | ↓N/E-cadherin, MMP9, vimentin, EMT | [81] |
HepG2215 cells | DHA | 100 μM | ↓Migration ability; | [55] | |
HCCLM3 and MHCC97H cells | ART | 25–100 μM | ↓N-cadherin, MMP2, MMP9, Snail, E-cadherin | [60] | |
HCCLM6 cells | DHA | 50–100 μM | ↓FN1, ITGB1 | [59] | |
HepG2 and SMMC-7721 cells | ART | 12.5–75 μM | ↓MMP2; ↑TIMP2 | [82] | |
HepG2 cells | ART | 6.25–50 mmol/L | ↓VEGF, PIGF | [83] | |
HepG2 and Huh7 cells | ART | 25 μM , 125 μM | ↓Cell migration | [84] | |
Effects on hepatic stellate cells | |||||
Liver fibrosis | Mouse HSCs and LX-2 cells | ART | 25–75 μM | ↓Cell vaibility, GSH, GPX4, NADPH, α-SMA, collagen 1, fibronectin, desmin, FTH1, NCOA4, p62; ↑cell death, Fe2+ accumulation, LPO, MDA, ROS, ferroptosis, LC3; mitochondria morphology change | [87] |
HSC-T6 cells | ARM | 10–40 ug/ml | ↓α-SMA, collagen 1, fibronectin, TGF-β, PDGF-β, EGF, cell viability, GSH, NADPH, Gpx4, SLC7A11; ↑cell death, Fe2+, ROS1, ferroptosis, p53; mitochondria morphology change | [88] | |
LX-2 cells | ARM | 10–40 ug/ml | ↓cell activation; ↑cell death, Fe2+, ROS, MDA, LPO, ferroptosis, IRP2 | [89] | |
LX-2 cells | ART | 12.5–50 ug/ml | ↓cell activation, α-SMA, collagen 1, p-Akt, p-FAK, p-GSK-3β | [64] | |
LX-2 cells | ART | 350umol/L | ↓hydroxyproline; ↑ceramide synthase protein, ceramide, PPAR-γ, caspase-3 | [90] | |
LX-2 cells | ART | 50–200 μM | ↓cell viability, Col1a1, Col3a1, OGDH, CS, IDH2, mitochondrial function, NDUFB8, UQCRC2; ↑Cell apoptosis | [91] | |
Effects on cell autophagy | |||||
Liver fibrosis | Primary rat HSCs | DHA | 5–20 μM | ↓P62, inflammatory factors, GSH/GSSG; ↑autophagosome, autophagic flux, LC3-II, ROS, p-JNK1/2 | [54] |
Primary rat HSCs | DHA | 5–20 μM | ↑autophagosome, p-ULK1, p-mTOR, Atg6/Beclin1, LC3-II, p53, GATA6, cell senescence | [99] | |
HCC | HepG2215 cells | DHA | 100 μM | ↓p-AKT, p-mTOR, p-p70S6K, p-4EBP1; ↑LC3, p-AMPK, p62 | [55] |
HepG2215 cells | DHA | 21.5 μM | ↓p62/SQSTM1; ↑LC3B-II | [56] | |
Effects on chemsensitization to chemotherapeutic agents | |||||
HCC | SM-7721, SK-hep1 cells | ART | 50 μM | Chemosensitize with Sor, ↓IC50, cell viability, p-RAF, p-ERK, p-AKT, p-mTOR; ↑cell apoptosis, p-PARP | [93] |
HepG2 cells Huh7 cells | ART | 25 μM 125 μM | Chemosensitize with Sor, ↓IC50, VEGFR2; ↑cell apoptosis, cleaved caspase-9, cleaved PARP | [84] | |
HepG2 and Hep3B cells | ART and DHA | 10 μmol/L | Chemosensitize with gemcitabine, ↓cell survival | [51] | |
Hep3B cells | DHA | 5 μM | Chemosensitize with ADM, ↓cell viability, clone, P-gp, p-ERK1/2, p65; ↑cell apoptosis | [95] |