Table 2.
Effect of fucoxanthin (Fx)-rich brown algal extract, Fx and fucoxanthinol (FxOH) in human colorectal cancer cell lines.
| Brown Algal Extract or Compound (Additive Concentration) |
Cell Line (Cell Type) |
Promoted Molecular Mechanism(s) | Involved Intracellular Component | Final Outcome (Cell Function) |
Reference |
|---|---|---|---|---|---|
| Ethanol extract of Undaria pinnatifida sporophyll (~2.0%) | HCT116 (PCs) |
Caspase-3 activation, and non-oxidative mechanisms differed from those of 5-fluorouracil and irinotecan treatments | NA | Apoptosis | [78] |
| Ethanol extract of Dictyopteris undulata sporophyll (~200 μg/mL) |
SW480 (PCs) |
Augmentation of endoplasmic reticulum stress; attenuation of mitochondrial membrane potential; increases of Bax, caspase-3, caspase-9, caspase-12, phospho-PERK, phospho-IRE1, cleaved ATF6, and CAAT/enhancer-binding protein-homologous protein; and decrease of Bcl-2 | Endoplasmic reticulum, and mitochondria | Apoptosis | [79,80] |
| Methanol extract of Pylaiella littoralis (~100 μg/mL) | HT-29 (PCs) |
Attenuation of mitochondrial membrane potential, decrease of Bcl-2, and increases of Bax, active caspase-3 form, cleaved PARP, phospho-JNK, phospho-ERK and p38 | Mitochondria | Apoptosis | [81] |
| Ethanol extracts of Turbinaria ornata and Padina pavonia
(~50 μg/mL) |
HCT116 (PCs) |
NA | Growth inhibition | [82] | |
| Organic fraction of Cystoseira sedoides (~500 μg/mL) | HCT115 (PCs) |
NA | Growth inhibition, antioxidation and anti-inflammation | [83] | |
| FxOH (~5.0 μM) | DLD-1 (PCs) |
Alterations of gene set belonging cell cycle, integrin, PI3K/AKT, MAPK, NRF2, adipogenesis, TGF-β, STAT and WNT/β-catenin signals, decreases of cyclin D1, cyclin D2, integrin α5, integrin β1, phospho-Paxillin(Tyr31), phospho-AKT(Ser473), phospho-C-Raf (Ser338), phospho-MEK1/2(Ser217/221), PPARγ and phospho-Smad2(Ser465/467), and increases of phospho-ERK1/2(Thr202/Tyr204) and NRF2 | NA | Apoptosis | [84] |
| FxOH (~5.0 μM) | DLD-1 (PCs) |
Arrest of G2/M cell cycle phase, decreases of CLIC4, integrin β1, phospho-Smad2(Ser465/467) and NHERF2 | NA | Apoptosis | [85] |
| FxOH (~2.5 μM) | DLD-1 (PCs) |
Alteration on cellular distribution of integrin β1, and decreases of phospho-FAK(Tyr397), phospho-AKT(Ser473) and PPARγ | NA | Anoikis | [86] |
| FxOH (~10 μM) | HCT116 (PCs) |
Arrest of G0/G1 cell cycle phase, activations of NF-κB and caspase-3, and increases of XIAP and cIAP-1 | NA | Apoptosis | [87] |
| Fx (~100 μM) | HCT116 and HT-29 (Both PCs) |
Increase of p53 and decrease of Bcl-2 in HCT116 cells, and increase of Bax and decrease of pro-caspase-9 in HT-29 cells | NA | Growth inhibition | [88] |
| Fx (~75 μM) | WiDr | Arrest of G0/G1 cell cycle phase, and increases of p21WAF1/Cip1 and p27Kip1, and decreases of phospho-pRb(Ser780), phospho-pRb(Ser807/811), cyclin D1, cyclin D2 and cyclin D3 | NA | Apoptosis | [89] |
| Fx (~15.2 μM) | Caco-2 | Decrease of Bcl-2 and activation of caspases | NA | Apoptosis | [90] |
| FxOH (~25 μM) | Caco-2 | NA | Growth inhibition | [91] | |
| Fx (~30 μM) | SW-620 | Loss of adhesion and invasion activities, and decrease of MMP-9 | NA | Growth inhibition | [92] |
| Fx and FxOH (~20 μM) | Primary cells in CRC patients | NA | Growth inhibition | [93] | |
| FxOH (~5.0 μM in vitro, 5 mg/kg body weight in vivo) | HT-29 (Csps) |
Decreases of phospho-AKT(Ser473), PPARβ/δ and PPARγ, suppression of tumorigenesis in NOD/SCID mice | NA | Apoptosis | [97] |
| FxOH (~50 μM) | HT-29 (Csps) |
Suppressions of cell migration and invasion; attenuations of EMT, integrin, MAPK and STAT signal proteins; decrease of p53; and increase of active caspase-3 form | NA | Apoptosis under normoxia condition | [98] |
| FxOH (~50 μM) | HT-29 (Csps) |
Attenuations of EMT, integrin, MAPK and STAT signal proteins; decreases of HIF-1α, cyclin D1and p53; and increases of phospho-β-catenin(Ser31/37/Thr42) and active caspase-3 form | NA | Apoptosis under hypoxia condition | [99] |
Parent cells (PCs) indicate each intact cell line, most of which are the adherent types. Colonospheres (Csps) indicate a spheroid prepared from the parent cells by stem cell medium and some growth factors. Fx, fucoxanthin; FxOH, fucoxanthinol; NA, not available; PERK, protein kinase RNA (PKR)-like ER kinase; IRE1, inositol-requiring enzyme 1; ATF6, activating transcription factor 6; PARP, poly(ADP-ribose) polymerase; JNK, c-Jun NH2-terminal kinase; ERK, mitogen-activated protein kinase 1; PI3K/AKT, phosphatidylino-sitol-3 kinase/protein kinase B; MAPK, mitogen-activated protein kinase; NRF2, nuclear factor erythroid 2 [NF-E2]-related factor 2; TGF-β, transforming growth factor beta; STAT, signal transducers and activators of transcription; WNT, wingless/integrated; MEK, mitogen-activated protein/extracellular signal-regulated kinase; PPARγ, peroxisome proliferator activated receptor gamma; CLIC4, chloride intracellular channel 4; NHERF2, Na+/H+ exchanger regulatory factor 2; FAK, focal adhesion kinase; NF-κB, nuclear factor-κB; XIAP, X-linked inhibitor of apoptosis protein; cIAP-1, cellular inhibitor of apoptosis protein-1; MMP-9, matrix metallopeptidase 9; PPARβ/δ, peroxisome proliferator activated receptor beta/delta; NOD/SCID, NOD.CB17-Prkdcscid/J; EMT, epithelial-mesenchymal transition; HIF-1α, hypoxia-inducible factor-1 alpha.