Table 7.
Impact of resveratrol on the expression of genes in the context of gastrointestinal cancers
| Type of cancer | Dose range | Cell line | Target | Pathway | Function | Refs. |
|---|---|---|---|---|---|---|
| In vivo studies | ||||||
| Gastric cancer (GC) | 50 mg/kg, 10–200 mg/L | SGC7901, SGC7901/DOX, MGC803 | TSC1, TSC2, p70S6K, Caspase-3/9, Vimentin, E-cadherin | PTEN/AKT, mTOR | RVT via modulating PTEN/AKT pathway by inhibiting EMT could reverse doxorubicin resistance in GC | [67] |
| Hepatocellular Carcinoma (HCC) | 0–100 mg/kg, 20–80 μM | HepG2, Hep3B | MARCH-1, STAT3, VEGF, Bcl-2 | PTEN/AKT | RVT via MARCH-1-induced regulation of the PTEN/AKT pathway and inhibit malignant progression of HCC | [65] |
| Colorectal Cancer (CRC) | 1 mg/kg 5 μg/mL | HCT116, CT26 | Cx43, EGFR, NF-kB p65, IKKa, IkBa, | AKT, PI3K, mTOR, MAPK | RVT via upregulating connexin43 and inhibition of the AKT pathway could sensitize CRC cells to cetuximab | [66] |
| CRC | 50–150 mg/kg , 0–80 μM | HCT116, SW480 | PCNA, Caspase-3, GSK-3β, | PTEN/PI3K/AKT, Wnt/β-catenin | RVT via the Wnt/β-catenin and PTEN/PI3K/AKT pathways could play a role in human colon cancer cell proliferation | [68] |
| CRC | 150 mg/kg, 0–240 μmol/L | SW480 and SW620 | N-cadherin, E-cadherin, Vimentin | AKT/GSK-3β/Snail | RVT via the AKT/GSK‑3β/Snail pathway could inhibit the metastasis and invasion of CRC cells | [69] |
| In vitro studies | ||||||
| Gastric intestinal metaplasia (GIM) | 200 μM | GES-1, AGS, BGC823, SGC7901, MKN45, MKN28, AZ521, HCT116 | CDX2, Villin1, Klf4, Cadherin17, Muc2 | PI3K/AKT/p-FoxO4 | RVT via the PI3K/AKT/p-FoxO4 pathway could inhibit bile acid-induced GIM | [63] |
| GC | 50–200 μmol/L | MGC803 | GSK3β, Cyclin-D1 | PTEN/ PI3K/ AKT | RVT via regulating the PTEN/ PI3K/AKT pathway could induce cell cycle arrest in human gastric cancer MGC803 cells | [64] |
| HCC | 0–200 μM | HepG2 | FoxO3a/Bim | AKT | RVT via modulating AKT/FoxO3a/Bim pathway could induce apoptosis in HepG2 cells | [70] |
| HCC | 100 μM | HepG2, Bel-7402, SMMC-7721 | SIRT1, Bcl-2, Caspase-3/7, PARP, PCNA, Bax | PI3K/AKT | RVT via SIRT1 mediated post-translational modification of PI3K/AKT signaling could inhibit migration and proliferation in HCC cells | [71] |
| CRC | 10–40 μM | DLD1, HCT15 | Cyclin-D1, Cyclin-E2, Bcl-2, p53, Bax | AKT/STAT3 | RVT via targeting the AKT/STAT3 pathway could suppress colon cancer growth | [72] |
| CRC | 40–60 μM | HCT116, 293 T | BMP7, GFP, PTEN, BAD, Bcl-2, Smad1/5/8 | PI3K/AKT | RVT via upregulating BMP7 could inactivate PI3K/AKT signaling in human colon cancer cells | [73] |
Concentration of resveratrol and its metabolites has been assessed in the colorectal tissues of humans who received resveratrol in a clinical study on colorectal cancer patients who took eight daily doses of resveratrol at 0.5 or 1.0 g prior to surgical resection of tumors. This study ahs confirmed tolerability of resveratrol. More importantly, these doses of resveratrol have been shown to produce sufficient concentrations for induction of anti-cancer effect in the gastrointestinal tract [74]