Table 4.
Anticancer activities of aporphine alkaloids on various cancer types.
| Cancer type | Constituents | Model/Cell (IC50) |
Dose | Effects | Mechanisms | Ref | |
|---|---|---|---|---|---|---|---|
| In vivo | Hepatocellular carcinoma | Isocorydine | Murine Model with SP cells from MHCC-97L cells | 0.4 mg/kg (IP) | ↓Tumor volume; ↓Tumor weight | ↑Fas; ↑Bax; ↑Bim; ↑Bik; ↑Bak; ↑puma;↓Bcl-2; ↓Bcl-xl; ↓Mcl-1 | [99] |
| Isocorydine | Murine Model with Huh7 or SMMC-7721 cells | 0.4 mg/kg (IP) | ↓Tumor volume; ↓Tumor weight | ↑p-Chk1; ↑p-Chk2 | [119] | ||
| 8-acetamino-isocorydine | Murine Model with H22 cells | 100 mg/kg (oral) | ↓Tumor umor volume; ↓Tumor weight | – | [35] | ||
| 8-amino- isocorydine | Murine model with HCC-LY5 cells | 0.12 mg/mice (IP) | ↓Tumor weights; ↓Tumor volumes | ↑C/EBPβ | [100] | ||
| Boldine | Rats model treated by diethylnitrosamine | 90 mg/kg (oral) | ↑Liver weight | ↓Bcl2; ↑Bax; ↑cytochrome c; ↑cleaved caspase 3 | [94] | ||
| Oxoglaucine | Murine model of hepatoma with BEL-7402 cells | 75 mg/kg (IP) | ↑Tumor growth inhibition rate | – | [95] | ||
| Chiral platinum (II)-4-(2,3-dihydroxypropyl)-formamide oxoaporphine | Murine model with BEL-7404 and BEL-7402 cells | 8 mg/kg (IP) | ↓Tumor growth | ↓hTERT; ↓ c-myc | [103] | ||
| cobalt oxoisoaporphine complexes | Murine model with BEL-7402 and T-24 cells | 5 mg/kg (IP) | ↓Tumor growth | ↑ROS; ↑Apaf-1; ↑cytochrome c; ↑caspase-3/9 | [145] | ||
| Oxoaporphine-Zn complexes | Murine model with HepG2 cells | 6 mg/kg (IP) | ↓Tumor weights; ↓Tumor volumes | ↑p53; ↑p21; ↑p27; ↑Chk1; ↑Chk2 | [105] | ||
| Magnoflorine | Murine model with SGC7901 cells | 10 mg/kg (IP) | ↓Tumor cell density | ↓AKT; ↑JNK | [110] | ||
| Colorectal cancer | Nuciferine | Murine model with CT26 cells and SY5Y cells | 1 mg/mL (IP) | ↓Tumor weights | ↓PI3K-AKT and IL-1β levels | [96] | |
| Organoplatinum (II) complexes with Oxoisoaporphine | Murine model with NCI-H460 cells | 6 mg/kg (IP) | ↓Tumor weights; ↓ volumes | ↑Caspase-3/9; ↓Telomerase | [104] | ||
| Pancreatic cancer | Isocorydine | murine model with PANC-1 cells | 0.4 mg/kg (IP) | ↓Tumor weights; ↓Tumor volumes | ↓p-STAT3 | [106] | |
| Nuciferine | Murine model with PANC-1 cells | 30 mg/kg (IP) | ↓Tumor volume; ↓Tumor weight | ↓pYAP | [107] | ||
| Lung cancer | Nuciferine | Murine model with A549 cells | 50 mg/kg (IP) | ↓Tumor weight; ↓Tumor size | ↑Axin; ↑Bax; ↓β-catenin; ↓Bcl-2 | [97] | |
| Nuciferine | Murine model with LA795 cells | 30 μM (oral) | ↓Tumor growth | ↓TMEM16A | [2] | ||
| Nuciferine | Murine model with A549/T cells | 7.5 mg/kg (IP) | ↓Tumor growth; ↓Tumor size | ↓PI3K/AKT | [108] | ||
| Glioblastoma | Nuciferine | Murine model with U251 cells | 15 mg/kg (IP) | ↓Tumor size, ↓angiogenesis; ↓hardness index | ↓p-AKT; ↓p-STAT3; ↓SOX2 | [120] | |
| Breast cancer | Boldine | Rat model with LA7 cells. | 100 mg/kg (IP) | ↓Tumor growth | ↑caspase-3/7; ↓NF-κB | [111], [114] | |
| KO-202125 | Murine model with MDA-MB-231 cells | 1.95 mg⁄kg (oral) | ↓Tumor growth | ↓AKT | [111] | ||
| Magnoflorine | Murine model with MCF-7 cells. | 3 mg/kg (IP) | ↓Tumor volume; ↓Tumor weight | ↑caspase-3; ↑LC3-II; ↑p-p38 | [20] | ||
| 7-hydroxydehydronuciferine | Murine model with A375.S2 cells | 20 mg/kg (IP) | ↓Tumor size | ↑PI3k/AKT | [121] | ||
| Apomorphine | Zebrafish transgenic model | 50 μM | ↓Vascular formation | – | [19] | ||
| In vitro | Hepatocellular carcinoma | Magnoflorine | HepG-2 (0.4 μg/mL)U251 (7 μg/mL) |
1–10 μg/mL | ↓Cell viability | – | [39] |
| Lanuginosine | HepG-2 (2.5 μg/mL)U251 (4 μg/mL) |
1–10 μg/mL | |||||
| Xylopine | HepG-2 (6.31 μM) | 5, 10 μg/mL | ↑Cytotoxicity | ↑G2/M arrest | [101] | ||
| Xylopine | HepG-2 (9.4 μM) | 14 μM | ↑Cytotoxicity | ↑G2/M phase arrest; ↑p53-independent pathway | [122] | ||
| Boldine | HepG-2 (55.66 ± 1.3 μM) | 50 μg/mL | ↓Cell viability | ↑G2/M arrest, ↑caspase-9 and caspase-3/7 | [125] | ||
| 8-hydroxyartabonatine C | HepG-2 (12.9 μM) | 60 μM | ↑Cytotoxicity | – | [135] | ||
| ouregidione | HepG-2 (26.3 μM) | 60 μM | ↑Cytotoxicity | – | |||
| Platinum (II) complex of Liriodenine | BEL-7404 (6.9 μM) | 10 μM | ↓Cell proliferation | ↑S/G2/M phase arrest; ↓Telomerase | [103] | ||
| Gastric cancer | 7-hydroxydehydronuciferine | AGS (62.9 μM) | 100 μM | ↓Cell proliferation | – | [41] | |
| Colorectal cancer | Xylopine | HCT-116 (6.4 μM) | 14 μM | ↑Cytotoxicity | ↑G2/M phase arrest; ↑p53-independent pathway | [122] | |
| D-dicentrine analogues | COLO 201 (3.9 μM) | 10 μM | ↑Apoptosis | ↓TOP2; ↑G2/M arrest | [146] | ||
| Lung cancer | Crebanine | A549 (25 μg/mL) | 5–15 μg/mL | ↓Proliferation; ↓Migration | ↑TNF-α; ↓NF-κB;↓Bcl-2 | [147] | |
| Thailandine | A549 (0.30 μg/mL) | 50 μg/mL | ↑Cytotoxicity | – | [139] | ||
| Magnoflorine with cisplatin | NCIH-1277 (36.5 µg/mL) | – | ↓Proliferation; ↓Migration | ↑p53; ↑caspase-3; ↑LC3-II; ↑p-p38;↓p-AKT | [118] | ||
| Laryngeal Squamous Cell Carcinoma | Xylopine | SCC9 (26.6 μM); HSC3 (15.7 μM) | 14 μM | ↑Cytotoxicity | ↑G2/M phase arrest; ↑ p53-independent pathway | [122] | |
| Glioblastoma | Magnoflorine | U251(7 μg/mL) | 1.1 mg/mL | ↓Cell viability | – | [39] | |
| lanuginosine | U251 (4 μg/mL) | 1.1 mg/mL | ↓Cell viability | – | |||
| AAs isolated from Thalictrum foetidum | GSC-3#, GSC-18# (2.36–5.37 μg/mL) | 0.5–60 μg/mL | ↓Cell viability | – | [93] | ||
| Breast cancer | Boldine | MCF-7 (160 µM) | 63–2000 μM | ↓Proliferation | ↓Telomerase | [125] | |
| N-benzylsecoboldine | MCF7(16.25 µM); MDA-MB-231 (21.88 µM) | – | ↓Cell viability | ↓Telomerase | [124] | ||
| Crebanine | MCF-7 cells (27 μg/mL)MDA-MB231 (15 μg/mL) |
5–15 μg/mL | ↓Cell viability | ↑TNF-α; ↓NF-κB;↓Bcl-2 | [147] | ||
| Oxocrebaine | MCF-7 (16.66 μM) | 4–64 μmol/L | ↓Proliferation; ↓migration | ↑DNA damage; ↑Autophagy | [126] | ||
| Four AAs isolated from Stephania venosa Spreng | MDA-MB231 (4–40 μg/mL) | 1 mg/mL | ↓Proliferation | ↑G2/M arrest; ↑Apoptosis | [139] | ||
| Two AAs isolated from Fissistigma glaucescens | MCF-7 (3.2–8.1 μg/mL) | – | ↑Cytotoxicity | – | [43] | ||
| Xylopine | MCF-7 (12 μM) | 14 μM | ↑Cytotoxicity | ↑G2/M phase arrest; ↑ p53-independent pathway | [122] | ||
| Four AAs isolated from Stephania venosa Spreng | MCF-7 (22.2 μM; 23.9 μM) | 1 mg/mL | ↑Cytotoxicity | – | [139] | ||
| Melanoma | N-methylated nuciferine N-methylasimilobine(-) -lirinidine2-hydroxy-1-methoxy-6a,7-dehydroaporphine |
Melanogenesis 4A5 cells (15.8 μM; 14.5 μM; 19.3 μM; 13.3 μM) | 3–30 μM | ↓Melanogenesis | ↓Tyrosinase; ↓TRP-1; ↓TRP-2 | [42] | |
| Epithelial ovarian cancer | Liriodenine | CAOV-3 (37.3 μM) | 20–40 μM | ↓Cell viability | ↑S phase arrest; ↑caspase-3; ↑caspase-9 | [25] | |
| Osteoma cells | Magnoflorine with cisplatin | MG-63 (2.05 μM); U-2 osteoma (4.81 μM) | – | ↓Proliferation; ↓Invasion | ↑HMGB1; ↑ NF-κB; ↑ miR-410-3p | [118] | |
| Leukemia | Xylopine | HL-60 (18.5 μM)K562 (7.8 μM) |
14 μM 14 μM |
↑Cytotoxicity | ↑G2/M phase arrest; ↑ p53-independent pathway | [122] |
AKT: protein kinase B; AMPK: AMP-activated protein kinase; Apaf-1: the apoptotic protease activating factor-1;
CDK1/2: cyclin dependent kinases 1/2; hTERT: human telomerase reverse transcriptase; IP: intraperitoneal injection; IL: interleukin; JNK: stress-activated protein kinases; NF-κB: nuclear factor kB; PI3K: phosphatidylinositol 3-kinase; ROS: reactive oxygen species; STAT3: activator of transcription 3; SOX2: sex determining region Y (SRY)-box 2; TNF-α: tumor necrosis factor α; TMEM16A: the transmembrane protein 16A; YAP: YES-associated protein Ser127.