Table 1 Anti-tumoral effects of resveratrol in glioblastoma radiotherapy/chemotherapy
Model | Cell line(s) | Resveratrol dosage; route of administration | Exposure conditions of RT | Chemotherapeutic drug; dosage; route of administration | Co-treatment outcomes | Refs. |
|---|---|---|---|---|---|---|
In vitro | U-87MG | 20 µM | 5 Gy; 180 KV X-rays | – | Induction of a delay in cell cycle progression, enhancement of GJIC | [82] |
In vitro and in vivo | CD133 | 100 µM | 2, 4, 6, 8, and 10 Gy; 1.25 MeV (cobalt-60 γ-rays) | – | Induction of apoptosis, suppression of STAT3 signaling, ↑survival rate | [70] |
In vitro and in vivo | SU-2 | 75 µmol/L (for in vitro) and 150 mg/kg/day (for in vivo); ip | 2, 4 and 6 Gy; 6 MV X-rays | – | ↑radiosensitivity, prevention of self-renewal and stemness, ↑apoptosis, induction of autophagy, inhibition of DNA repair | [101] |
In vitro | U87MG | 20 µM | 2 Gy; 1.25 MeV (cobalt-60 γ-rays) | – | ↓colony number, ↑DNA damage, ↑radiosensitivity | [100] |
In vitro | DBTRG | 50 µM | – | Paclitaxel; 50 µM | ↑mitochondrial ROS levels, ↑activation of TRPM2 channel, ↑caspase 3 activity, ↑influx of Ca2+ into the cell through TRPM2 channel | [108] |
In vitro | T98G | 100 µM | – | Temozolomide; 100 µM | ↑chemosensitivity, ↑apoptotic morphology (such as nuclear and cytoplasmic condensation and chromatin aggregation), ↑cleavage of caspase-3, ↓intracellular level and nuclear translocation of NF-κB, repression of MGMT expression | [120] |
In vitro and in vivo | GIC400 andGIC411 | 20 and 40 µM (for in vitro) and 12.5 mg/kg/day (for in vivo); ip | – | Temozolomide; 200 and 400 µM (for in vitro) and 68 mg/kg/day (for in vivo); oral | ↓cell viability, induction of apoptosis, activation of DSBs/pATM/pATR/p53 pathway, inhibition of self-renewal capacity and promotion of cell differentiation, inactivation of STAT3, inhibition of tumor growth | [119] |
In vitro and in vivo | T98G and U138 | 2, 4, 8, 10, 16 and 32 µM (for in vitro) and 10 mg/kg/day; ip | – | Temozolomide; 400 µM (for in vitro) and 25 mg/kg//day (for in vivo); ip | ↓cell viability and proliferation, ↑apoptosis (↑Cleaved caspase-3 and Bax, ↓XIAP and Bcl‐2), suppression of Wnt signaling pathway, downregulation of MGMT expression | [121] |
In vitro | RG-2, LN-18 and LN-428 | 25, 50, 75 and 100 µM | – | Temozolomide; 250, 500, 750 and 1000 µM | Inhibition of growth cell, down-regulation of MGMT overexpression, ↓expression of STAT3, ↓survivin and Bcl-2 levels, Inhibition of STAT3/Bcl-2/survivin signaling pathway | [122] |
In vitro and in vivo | SHG44 | 10 µM (for in vitro) and 40 mg/kg/day (for in vivo); oral | – | Temozolomide; 100 µM (for in vitro) and 68 mg/kg/day (for in vivo); oral | Induction of cell cycle arrest in the G2/M phase, ↑expression of GFAP, down-regulation of MMP-9 expression, inhibition of cell migration, ↑ROS production, activation of AMPK, inhibition of mTOR signaling, down-regulation of Bcl-2, ↓tumor volume, ↓Ki-67 expression | [133] |
In vitro and in vivo | U87 MG | 10 µM (for in vitro) and 12.5 mg/kg/day (for in vivo); ip | – | Temozolomide; 100–400 µM (for in vitro) and 10 mg/kg/day (for in vivo); ip | ↓autophagy, ↑apoptosis, ↓cell viability, ↑chemosensitivity,↑cell death, ↓tumor volume, ↓ERK activity and LC3-II protein levels, ↑cleavage of PARP | [172] |
In vitro | U87, U138 and U251 | 30 µM | – | Temozolomide; 100 µM | ↑autophagy, abrogation of temozolomide-induced G2 arrest, ↑gammaH2AX, pATM and pChk2, ↑cyclin B and pRb levels, ↓pWee1 and pCdk1 levels, induction of mitotic catastrophe (aberrant chromosome condensation and mitotic phenotype, micronuclei and nuclearfragmentation, abnormal/triple mitosis, ↑percentages of irregular nuclei and large nuclei), ↓clonogenic growth, ↑senescence | [163] |
In vitro and in vivo | U251MG and C6 | 7.5, 15 and 30 µM and 10 mg/kg/day; ip | – | Temozolomide; 10 mg/kg/day and thrice a week; ip | Inhibition of temozolomide-induced autophagy and promotion of apoptosis (up to 15 µM resveratrol), inhibition of ERK1/2-dependent autophagy | [164] |