Table 3.
Antitumor activity of phlorotannins extracts and isolated phlorotannins from brown macroalgae.
| Extract/Compound | Model | Conditions | Effect | Ref. |
|---|---|---|---|---|
| Saccharina japonica | ||||
| MAE with EtOH 55% | HepG2 cells | Incubation with 0.2–2 mg/mL for 24 h | ↓ cell prolif. | [115] |
| Ascophyllum nodosum | ||||
| ACN:0.2% CH2O2 (1:1) → purification in SPE columns | Caco-2 cells | Incubation with 0–50 µg/mL for 72 h | ↓ cell prolif. (IC50 = 33 μg/mL) | [12] |
| Alaria esculenta | ||||
| ACN:0.2% CH2O2 (1:1) → purification in SPE columns | Caco-2 cells | Incubation with 0–50 µg/mL fot 72 h | ↓ cell prolif. (IC50 = 7 μg/mL) | [12] |
| Cystoria sedoides | ||||
| MAE with EtOH 50% | MCF-7 cells | Incubation with 10–200 µg/mL for 24 h | ↓ cell prolif. | [116] |
| Cystoseira spp. | ||||
| H2O extract | Tumor cells: A549, HCT15 and MCF-7 cells Normal cells: MDCK cells and rat fibroblasts |
Incubation with 25–250 µg/mL for 48 h | Tumor cells: ↓ cell prolif. (IC50 = 17.9–90.3 μg/mL) Normal cells: ↓ toxicity than cisplatin |
[113] |
| Fucus evanescens | ||||
| EtOH 60% | DLD-1 and HT-29 cells | Incubation with 50 µg/mL for 30 d | ↓ cell prolif. by 67% and 63%, respectively | [117] |
| Laminaria cichorioides | ||||
| EtOH 60% | DLD-1 and HT-29 cells | Incubation with 50 µg/mL for 30 d | ↓ cell prolif. by 64% and 56%, respectively (July specimen) ↓ cell prolif. by 50% and 52%, respectively (September specimen) |
[117] |
| Costaria costata | ||||
| EtOH 60% | DLD-1 and HT-29 cells | Incubation with 50 µg/mL for 30 d | ↓ cell prolif. by 38% and 31%, respectively (May’s specimen) ↓ cell prolif. by 50% and 44%, respectively (July specimen) |
[117] |
| Macrocystis integrifolia | ||||
| MeOH → Fract. with n-hex, H2O:EtOAc (2:3) and 1-But → subfraction of 1-But | HeLa cells | Incubation with 0.5–5 mg/mL for 72 h | ↓ cell prolif. (EC50 = 4.11 mg/mL) | [118] |
| Nereocystis leutkeana | ||||
| MeOH → Fract. with n-hex → H2O + EtOAc (2:3) → 1-But | HeLa cells | Incubation with 0.5–5 mg/mL for 72 h | ↓ cell prolif. (EC50 = 4.10 mg/mL) | [118] |
| Laminaria setchellii | ||||
| MeOH → Fract. with n-hex → H2O + EtOAc (2:3) → 1-But | HeLa cells | Incubation with 0.5–5 mg/mL for 72 h | ↓ cell prolif. (EC50 = 4.53 mg/mL) | [118] |
| Sargassum muticum | ||||
| PLE with EtOH 95% → Fract. with DCM → Ac → EtOH → EtOAC | HT-29 cells | Incubation with 12.5–100 µg/mL for 24, 48 and 72 h | ↓ cell prolif. by 50% after 24 h with 50 μg/mL of extract (Norway specimen) | [119] |
| Fucus vesiculosus | ||||
| Ac 99.5% → purification by HPLC | PancTu1, Panc89, Panc1 and Colo357 cells | Incubation with 0.01–100 µg/mL for 24 h | ↓ cell prolif., ↑ cell cycle inhibitors (EC50 = 17.35, 17.5, 19.23 and 28.9 μg/mL, for each cell line, respectively) | [120] |
| Ecklonia cava | ||||
| MeOH 70% → Fract. n-hex → DCM → EtOAc | A549 cells | Incubation with 0–200 µg/mL for 24 or 48 h | ↓ exp. of MMP-2 | [121] |
| EtOH 95% | HDFs and HT1080 cells | Incubation with 10–1000 µg/mL for 3 d | ↓ exp. of MMP-2 and -9 | [122] |
| EtOH extract | A2780 and SKOV3 cells | Incubation with serial dilutions for 24 h | ↓ cell prolif. (IC50 = 84.3 and 99.6 μg/mL, respectively) | [114] |
| Ishige okamurae | ||||
| EtOH → Fract. H2O → n-But → MeOH 85% → n-hex | HT1080 cells | Incubation with 5 or 50 µg/mL for 24 h | ↓ exp. of MMP-2 and -9; ↑ exp. TIMP-1 and -2 | [123] |
| Isolated compounds | ||||
| 6,6’-Bieckol from Ecklonia cava | HT1080 cells | Incubation with 5–100 µg/mL for 48 h | ↓ exp. of MMP-2 and -9 and exp. of NF-κB p50 and p65 | [124] |
| Dieckol commercial | In vitro: SKOV3 cells In vivo: SKOV3-xenograft in BALB/c mice |
In vitro: Incubation with 80–120 µM for 24 h In vivo: oral administration of 50 and 100 mg/mL 3 d a week for 28 days |
In vitro: ↑ exp. of casp-3, -8 and -9; ↓ exp. of the XIAP, FLIP and Bcl-2 In vivo: ↓ cell prolif. and lower toxicity than cisplatin |
[114] |
| A549 cells | Incubation with 25–50 µg/mL for 24 h | ↑ exp. of casp-3, -8 and -9, of tumor suppressor protein E-cadherin | [125] | |
| Dieckol from Ecklonia cava | NDEA-induced Wistar rats | Oral administration of 40 mg/kg/d for 15 weeks | ↓ exp. of Bcl-2, VEGF, MMP-2 and -9, ↑ exp. of Bax, cytochrome c and casp-3 | [126] |
| MCF-7 cells | Incubation with 1–100 µM for 48 h | ↓ cell migration, exp. of MMP-9 and VEGF, ↑ exp. of TIMP-1 and -2 | [127] | |
| TPA-induced SK-Hep1 cells | Incubation with 1–50 µM for 1.5 h | ↓ exp. of MMP-9 and exp. of p-ERK 1/2, p-MEK 1/2 and p-JNK 1/2 | [128] | |
| LPS-induced MDA-MB-231 cells | Incubation with 50 µM for 48 h | ↓ cell invasion, exp. of TLR-4, NF-κB and MMP-2 and -9 | [129] | |
| Dieckol from Ecklonia stolonifera | Hep3B cells | Incubation with 70–110 µM for 24 h | ↑ exp. of casp -3, -7, -8 and -9, Bid and Bim | [130] |
| Eckol commercial | S180-xenograft in Kumming mice | Oral administration of 0.25–1 mg/kg/d for 7 d before and 10 d after xenograft | ↑ exp. of casp-3 and -9, ↓ exp. of Bcl-2, Bax, EGFR and p-EGFR |
[131] |
| Eckstolonol from Ecklonia cava | MCF-7 cells | Incubation with 5–110 µM for 48 h | ↓ exp. of Bcl-2, ↑ exp. of casp-3 and -9, Bax and tumor suppressor p53 | [132] |
| Phloroglucinol commercial | HT-29 cells | Incubation with 12.5–50 µg/mL for 24 h | ↑ exp. of casp-3 and -8, cytochrome c, Apaf-1, Bad and Bax, ↓ exp. of Bcl-2, Bcl-XL | [133] |
| HT-29 cells | Incubation with 0–50 µg/mL for 24 h | ↓ exp. of IGFR-1 | [134] | |
| Phlorofucofuroeckol A from Eisinia bicyclis | HCT116, SW480, LoVo and HT-29 cells | Incubation with 100 µM for 24 h | ↑ exp. of ATF3 | [135] |
| Phlorofucofuroeckol A from Ecklonia cava | LPS-induced MDA-MB-231 cells | Incubation with 50 µM for 48 h | ↓ cell invasion, exp. of TLR-4, NF-κB and MMP-2 and -9 | [129] |
↓—decrease; ↑—increase; ACN—acetonitrile; Apaf-1—apoptotic protease activating factor 1; ATF3—cyclic AMP-dependent transcription factor; Bad—Bcl-2 associated agonist of cell death; Bax—Bcl-2-associated X protein; Bcl-2—B-cell lymphoma 2; Bcl-XL—B-cell lymphoma-extra-large; Bid—BH3 interacting domain death agonist; Bim—Bcl-2-like protein 11; DCM—dichloromethane; ERK 1/2 —extracellular signal—regulated kinase 1 and 2; EGFR—epiderma growth factor; CH2O2—formic acid; MeOH—methanol; Ac—acetone; EtOH—ethanol; EtOAc—ethyl acetate; n-hex—n-hexane; n/1-But—n/1-buthanol; FLIP—FLICE-inhibitory protein; HPLC—high performance liquid chromatography; IGFR-1—insulin-like growth factor 1 receptor; MAE—microwave-assisted extraction; p-MEK 1/2—phosphor-MAP kinase kinase 1 and 2; SPE—solid phase extraction; PLE—pressurized liquid extraction; NF-κB—nuclear factor κB; NDEA—N-nitrosodiethylamine; p-JNK 1/2—phospho-c-Jun N-terminal kinase 1 and 2; TLR-4—Toll-like receptor 4; TPA—12-O-Tetradecanoylphorbol-13-acetate; LPS—lipopolysaccharides; MMP—matrix metalloproteinase; exp.—expression; prolif.—proliferation; casp—caspase; TIMP—tissue inhibitor of metalloproteinases; VEGF—vascular endothelial growth factor; XIAP—X-linked inhibitor of apoptosis protein. Cell lines: caco-2—human colon cancer; MDCK—Mardin–Darby canine kidney; HeLa—human cervical adenocarcinoma; PancTu1—human pancreatic cancer; Colo357—human pancreatic adenosquamous carcinoma; Panc89—human pancreatic cancer; and Panc1—pancreatic carcinoma; A549—human lung adenocarcinoma; MCF-7—human breast adenocarcinoma; HCT15—human colorectal adenocarcinoma; DLD-1—human colorectal adenocarcinoma; HT-29—human colorectal adenocarcinoma; Hep3B—human hepatocellular carcinoma; HDFs—human dermal fibroblasts; SK-Hep1—human hepatocellular carcinoma; HT1080—human fibrosarcoma; HCT116—human colon cancer; SW480—human colon cancer; LoVo—human colorectal cancer; A2780—human ovarian carcinoma; SKOV3—human ovarian carcinoma; MDA-MB-231—human breast cancer; S180—murine sarcoma cancer; HepG2—human liver hepatocellular carcinoma.