Table 8.
Effect of marine phenolics on the prevention of cancer.
| Compounds/Marine Source | Test Model | Outcome | Ref. |
|---|---|---|---|
| Dietary seaweed intake (gim, miyeok, and dashima) | In vivo: 923 colorectal cancer patients and 1846 controls | Association between c-MYC rs6983267 and colorectal cancer risk Inverse association between dietary seaweed intake and colorectal cancer risk |
[248] |
| Aqueous extract derived from brown Cystoseira crinita | In vitro: HCT15 and MCF7 cells (25–250 μg/mL for extracts) | Antiproliferative activity (IC50 of 10.5–26.4 μg/mL on HCT15 and 17.9–29.5 μg/mL for 24 h) associated with phenolic content and antioxidant activity | [249] |
| Phlorotannin-rich extract from A. nodosum | In vitro: HT29 cells (100–500 μg/mL for extracts) | Antiproliferative activity | [250] |
| Ethanolic extract from S. muticum rich in phlorotannins | In vitro: HT29 cells (12.5–100 μg/mL for extracts) | Antiproliferative activity (IC50 of ~53.5–57.9, 55.0–57.8 and 59.4–74.0 μg/L for 24, 48 and 72 h of treatment of S. muticum extracts) | [127] |
| Phlorotannins isolated from Ecklonia maxima (phloroglucinol, eckol, 7-phloroeckol and 2-phloroeckol) | In vitro: HeLa, H157 and MCF7 cells (6.25–500 μg/mL for phenol) | Antiproliferative activity: eckol was the most active of all the tested phlorotannins against HeLa and MCF7 cells after 24 of treatment (IC50 < 50 μg/mL) | [251] |
| Alcoholic extract from red (Gracillaria corticata), green (Ulva fasciata) and brown (Sargassum ilicifolium) seaweeds | In vitro: MCF-7, MDA-MB-231, HeLa, HepG2 and HT-29 cells (15–300 μg/mL for extracts) | Antiproliferative activity: G. corticata extract had the greatest activity against MCF-7 cells (IC50 of 30, 37, 53, 102 and 250 μg/mL on MCF-7, HeLa, MDA-MB-231, HepG2 and HT-29 cells, respectively, after 24 h of treatment) G. corticata extract induced the apoptosis in human breast cancer cells |
[252] |
| Phloroglucinol | In vitro: HCT116 and HT29 cells (10–300 μM of phenol) | Antiproliferative activity Intensified the 5-fluorouracil activity |
[253] |
| 3,4,5-Tribromo-2-(2’,4’-dibromophenoxy)-phenol (1) and 3,5-dibromo-2-(2’,4’-dibromophenoxy)-phenol (2) isolated from marine sponge Dysidea sp. | In vitro: PANC-1 cells under glucose-starved conditions (1–100 μM of phenol) | Antiproliferative activity (IC50 values of 2.1 and 3.8 μM for 1 and 2, respectively, after 12 h) Inhibition of the complex II in the mitochondrial electron transport chain |
[254] |
| Different extracts from F. vesiculosus L. rich in phlorotannins | In vitro: Panc89 and PancTU1 cells (0.8–500 μg/mL for crude extracts and 0.16–200 μg/mL for fractions) | Antiproliferative activity (IC50 of 72 μg/mL against Panc89 and of 77 μg/mL against PancTU1 cells after 72 h of treatment for the most active crude extract) | [24] |
| Extract from P. pavonica | In vitro: SaOS-2 and MNNG cells (0.5–2.5 μg/mL for extract) | Antiproliferative (IC50 value of 152.2 and 87.75 μg/mL for SaOS-2 and MNNG cells, respectively, after 24 h) and pro-apoptotic activities | [255] |
| Extracts of three brown marine macroalgae Dictyota dichotoma, Padaina pavonia and Sargassum vulgare | In vitro: LS174, A549, FemX, K562 cells (12.5–200 μg/mL for extract) | Characterization of the cytotoxic activity D. dichotoma showed the strongest cytotoxic activity of all the tested extracts (IC50 values ranging from 9.76 to 50.96 μg/mL after 72 h) |
[256] |
| Extracts from detached leaves of Posidonia oceanica and Zostera marina | In vitro: MCF-7, MDA-MB-231, SK-BR-3, HT-29, HeLa, PC-3 and Neuro 2A cells, as well as African green monkey kidney (VERO) (6.25–100 μg/mL for extract) | Characterization of the cytotoxic activity Z. marina extract showed the best IC50 values of 25, 20 and 8 μg/mL after 48 h in neuroblastoma, colon and cervix cancer cell lines, respectively |
[155] |
| Phlorotannin-rich fraction from Cystoseira sedoides | In vitro: MCF-7 cells (10–200 μg/mL for extract) | Characterization of the antiproliferative activity (IC50 value of 78 μg/mL after 72 h) | [257] |
| Crude extracts from two Egyptian brown seaweeds, Sargassum linearifolium and Cystoseira crinita | In vitro: a panel of cancer cells such as MCF-7 cells, among others (0.01–2000 μg/mL for extract) | Characterization of the cytotoxic activity. C. crinite cold methanolic extract showed a strong cytotoxic activity against MCF-7 cells (IC50 value of 18 μg/mL after 48 h) Induced the apoptosis and autophagy in MCF-7 cells |
[258] |
| Aqueous seaweed extracts of 23 different species in Sri Lanka | In vitro: L929 cells (10–100 μg/mL for extract) | Antiproliferative activity Crude extracts of brown and red seaweeds species have shown high mortality rate compared to green seaweeds Jania adherens showed a remarkable cytotoxic effect on L929 cell line (51% cell viability compared with control after 24 h) |
[259] |
| Ethanolic extract from E. cava whose main component was dieckol | In vitro: A2780 and SKOV3 cells | Cytotoxic effects on A2780 and SKOV3 ovarian cancer cells (IC50 ranging from 84 to 100 μg/mL for extract and from 77 to 169 μM for phenols, with dieckol being the most active of all, after 24 h) Induced the apoptosis on SKOV3 cells via Akt and p38 signaling pathways |
[260] |
| Phlorotannin-rich extract from E. cava rich in dieckol | In vitro: A2780 and SKOV3 cells (50–100 μg/mL) In vivo: SKOV3-bearing mouse model (75 and 150 mg/kg bw for extract and 50 and 100 mg/kg bw for dieckol was given orally three times/week for 4 weeks) |
Phlorotannin-rich extract may improve the efficacy of cisplatin for ovarian cancer by enhancing cancer cell apoptosis via the ROS/Akt/NFkB pathway | [261] |
| Phlorofucofuroeckol A present in E. bicyclis | In vitro: LoVo, HT-29, SW480 and HCT116 cells (25–100 μM of phenol) | Antiproliferative and pro-apoptotic properties Induced the apoptosis on colorectal cancer cells by ATF3 signaling pathway |
[262] |
| Ethanolic extract of H. fusiforme | In vitro: B16F10 cells (25–400 μg/mL of extract) | Cytotoxic activity Induced the apoptosis through activation of extrinsic and intrinsic apoptotic pathways and ROS-dependent inhibition of the PI3K/Akt signaling pathway |
[263] |
| Phlorotannin-rich extract from E. cava rich in phenolic compounds | In vitro: A549 cells (12.5–50 μg/mL of extract) | Inhibition of metastatic activity including suppression of migration and invasion Down-regulated the MMP-2 activity via PI3K/Akt |
[264] |
| Phloroglucinol isolated from E. cava | In vitro: MCF7, SKBR3 and BT549 cells (10–100 μM of phenol) In vivo: MDA-MB231 breast cancer cells implanted into mammary fat pads of NOD-scid gamma (NSG) mice, treated with phloroglucinol 4 times on alternate days (25 mg/kg bw by intratumoral injections) |
Antiproliferative effect by KRAS inhibition and its downstream PI3K/Akt and RAF-1/ERK signaling pathways Increased the sensitization of breast cancer cells to conventional therapy |
[265] |
| Phloroglucinol isolated from E. cava | In vitro: BT549 and MDA-MB-231 cells (10–100 μM of phenol) In vivo: GFP-labeled metastatic MDA-MB231 cells transplanted into mammary fat pads of NSG mice, treated with phloroglucinol 4 times on alternate days (25 mg/kg bw by intraperitoneal injection) |
Inhibited the metastatic ability of breast cancer cells Decreased the expression of SLUG, EMT master regulator through inhibition of PI3K⁄Akt and Ras⁄Raf-1 ⁄ERK Inhibited the in vivo metastatic ability of breast cancer cells |
[266] |
| Bis(2,3-dibromo-4,5-dihydroxybenzyl) ether | In vitro: HUVEC cells (12.5–50 μM of phenol) In vivo: Zebrafish embryos model (6.25–25 μM of phenol) |
Repressed the angiogenesis in both in vitro and in vivo models by inhibiting the VEGF signal systems | [267] |
| Dieckol from E. cava | In vivo: N-nitrosodiethylamime-induced hepatocarcinogenesis rats (40 mg/kg bw/day for 15 weeks administered orally) | Regulated the xenobiotic-metabolizing enzymes Induced the apoptosis by mitochondrial pathway Inhibited the invasion by decreasing PCNA expression Inhibited the angiogenesis by changing MMP-2 and MMP-9 activity and VEGF expression Anti-inflammatory activity by inhibiting NF-kB and COX2 |
[268] |
| Dieckol | In vitro: EA.hy926 cells (10–100 μM of phenol) | Antiangiogenic activity by inhibiting the proliferation and migration of cells through MAPK, ERK and p38 signaling pathways | [269] |
| Eckol | In vitro: on human HaCaT keratinocytes against PM2.5-induced cell damage (30 μM of phenol for 17 days) | Decreased the ROS generation Protected the cells from apoptosis by inhibiting MAPK signaling pathway |
[270] |
| Eckol | In vivo: sarcoma 180 (S180) xenograft-bearing animal model supplemented with low dose (0.25 mg/kg bw), middle dose (0.5 mg/kg bw) and high dose (1.0 mg/kg bw) of phenol administered orally | Proapoptotic and antiproliferative activities by improving the immune response | [271] |
| Polyphenol-rich extract from A. nodosum | In vivo: 80 overweight or obese population (100 mg/day of extract for 8 weeks) | Improvements in DNA damage in the obese subset | [30] |
ROS:reactive oxygen species; Akt: protein kinase B; NFkB: nuclear factor kappa B; ATF3: transcription factor 3; MMP: metalloproteinase; PI3k: phosphoinositide 3-kinase; VEGF: vascular endothelial growth factor; PCNA: proliferating cell nuclear antigen; COX-2: cyclooxygenase-2; MAPK: mitogen-activated protein kinase; ERK: extracellular signal-regulated kinase; DNA: deoxyribonucleic acid.