Table 1.
Studies on hydroxytyrosol (HT) and derivatives effects on cancer and cardiovascular diseases (CVDs) in the last five years.
| Sample | Treatments | Main Results | Ref. |
|---|---|---|---|
| CRC adenocarcinoma cells (DLD1) | HT (0–300 µM for 24 and 48 h) | HT induces ROS generation and leads to PI3K/Akt pathway activation, decreasing the antioxidant defense capacity through FOXO3a suppression. | [71] |
| Human CCA (TFK-1 and KMBC) and human gallbladder (GBS-SD) cancer cells | HT (0–200 μM for 24, 48 and 72 h) | HT induces cell cycle arrest and apoptosis. | [72] |
| Human hepatocellular carcinoma (HepG2, Hep3B, SK-HEP-1 and Huh-7) cells | HT (0–400 µM for 48 and 72 h) | HT can suppress the activation of Akt and NF-κB pathways. | [73] |
| Human breast (MDA and MCF-7), prostate (LNCap and PC3) and colon (SW480 and HCT116) cancer cells | HT (100 µM for 24, 48, 72, 96, 120 and 144 h) | HT inhibits the proliferation of all cell lines. | [74] |
| Human thyroid carcinoma (TPC-1 and FB-2), papillary and follicular (WRO) cells | HT (65–973 μM for 24 and 48 h) | HT reduces viability in all cell lines and exerts proapoptotic effects on papillary and follicular cancer cells. | [75] |
| Human colon cancer cells (Caco-2 and HT-29) | HT (100–200 μM for 8 and 48 h) | HT produces cell cycle arrest and promotes apoptosis. | [76] |
| Human umbilical vein endothelial cells (HUVECs) and dermal microvascular endothelial cells (HMVECs-d-Ad) | HT (0–50 μM for 18 and 24 h) | HT inhibits VEGFR-2 signaling pathway. | [77] |
| Male nude BALB/c mice cholangiocarcinoma xenograft (6–8 weeks old) | Intraperitoneally injected HT (500 mg/kg, daily, 3 weeks after the tumor volume reached ~120 mm3) | HT inhibits cholangiocarcinoma growth. | [72] |
| Orthotopic HCC model in nude mice cholangiocarcinoma xenograf (4–6 weeks old) | Intraperitoneally injected HT (10 mg/kg or 20 mg/kg, daily, 3 weeks starting 14 d after inoculation) | HT inhibits cholangiocarcinoma growth. | [73] |
| Human colon cancer (Caco-2) cells | HT (50 μM for 24 h) | HT up-regulates CNR1 gene via epigenetic regulation (decrease in methylation at CNR1 promoter), which is associated with reduced proliferation of Caco-2 cells. | [79] |
| Murine pre-adipocytes (3T3-L1) exposed to H2O2 | Pretreatment with HT (1 and 5 µM for 24 h) | HT blunts the H2O2-induced GSH/GSSG alteration. | [84] |
| Human umbilical cord vein endothelial cells (HUVEC) | HT, Tyr, and combination of both (10 µM for 30 min or 18 h) | The combination of HT with Tyr preserves cell functions from oxidative damage, which correlates with rescuing their antioxidant properties. | [85] |
| Human myelomonocytic cells (U937) and murine skeletal myoblasts (C2C12) exposed to H2O2 | Pretreatment with Laur-HT (5 µM), HT (20 µM) or both combined (20 µM) (for 30 min) | Laur-HyT has a protective antioxidant effect against H2O2 treatment, greater than HyT, so having a role in the prevention of apoptotic death in normal and tumor cells. | [86] |
| Human endothelial cells (ECV304) incubated with high glucose (30 mM) in the presence or absence of 0–120 mM FFAs (oleic or linoleic acid) | Co-treatment with HT (10 µM for 48 h) and polyphenol extract from EVOO (10 µM gallic acid equivalents for 48 h) | Treatments reduce the oxidative stress and modulate changes in NO and ET-1 associated with experimental conditions that simulate diabetes (hyperglycemia and a high level of FFA). | [87] |
| Human peripheral blood mononuclear cells (PBMC) and U937 monocytes activated with PMA (30 nM) | HT (1–10 μM for 0–24 h) prior to activation with PMA | HT blunts monocyte matrix invasive potential, reduces MMP-9 release and expression, and inhibits PGE2 production and COX-2 expression, which are mediated by inhibition of NF-κB transcription, PKCα and β1 activation. | [83] |
| Healthy subjects (22–37 years) | HT-enriched biscuits (30 g that contained 5.25 mg of HT) or Non-enriched biscuits (30 g) after overnight-fasting, only one meal in a cross-overdesing | Enriched biscuits consumption leads to a peak of posprandial levels of plasma metabolites (mainly 3,4-dihydroxyphenylacetic acid (DOPAC)-sulphate, DOPAC, HVA) between 0.5 and 1 h, which are also extensively excreted in urine and lower postprandial ox-LDL levels. | [88] |
| Volunteers with mild hyperlipidemia | HT purified (99.5%) from olive mill waste (5 mg, daily, for 8 weeks) | HT does not influence markers of CVD, blood lipids, inflammatory markers, liver or kidney functions and the electrolyte balance, but increased vitamin C levels. | [89] |
| Human hepatocarcinoma (HepG2) cells under tunicamycin-induced ER stress | HT or hepatic HT-derived metabolites 3-O-HT glucuronide and 4-O-HT glucuronide (10 and 25 μM for 24 h) prior to tunicamycin treatment | Both metabolites glucuronide inhibit ER stress, although they induce a milder change in mRNA expression levels of both CHOP and BiP. | [90] |