Table 1.
Summary of main in vitro and in vivo synergistic effects of combinations of stilbenes and chemotherapeutic compounds against CRC.
| References | Tested molecule | In combination with | Experimental model | Main result | Proposed mechanism |
|---|---|---|---|---|---|
| Ali and Braun, 2014 | Resveratrol | Mitomycin C | CRC cell culture (primary cell lines from resected colorectal tumors) | Synergistic suppression of cell proliferation by resveratrol and Mitomycin C | Up-regulation of p21WAF1/CIP1 |
| Amiri et al., 2013 | Resveratrol | Etoposide | CRC cell culture (HCT-116) | Synergistic effect of resveratrol on etoposide | Up-regulation of TP53 expression |
| Buhrmann et al., 2015 | Resveratrol | 5-Flourouracil | CRC cell culture (HCT-116, SW480) in a 3D-alginate microenviroment | Synergistic activity between resveratrol and 5-Fu decreasing viability and inducing apoptosis | Up-regulation of desmosomes, gap and tight junction adhesion molecules. Inhibition of EMT factors. Down-regulation of NF-kB activation |
| Kaminski et al., 2014 | Resveratrol | Oxaliplatin | CRC cell culture (Caco-2) | Positive: CRC cells chemosensitization by resveratrol. Synergistic activity of resveratrol and oxaliplatin inhibiting CRC cell growth | Induction of cell death |
| Kumazaki et al., 2013 | Resveratrol | 5-Fluorouracil | CRC cell culture (DLD-1, SW480, COLO201) | Synergistic enhancement of growth inhibition and apoptosis | Up-regulation of miR-34a expression causing a down-regulation of E2F3 |
| Majumdar et al., 2009 | Resveratrol | Curcumin | CRC cell culture (HCT-116) and mouse xenograft CRC models | Synergism between curcumin and resveratrol inhibiting growth of CRC cells in vitro and in vivo | Attenuation of NF-κB activity. Inhibition of constitutive activation of EGFR |
| Mohapatra et al., 2011 | Resveratrol | 5-Fluorouracil | CRC cell culture (HCT-116) | Synergistic induction of apoptosis | Cell cycle arrest in S phase, enhanced DNA damage |
| Santandreu et al., 2011 | Resveratrol | 5-Fluorouracil | CRC cell culture (HT-29, SW620) | Positive: Resveratrol sensitize CCR cells to 5-Fluorouracil | Increase in oxidative stress, inactivation or down-regulation of redox-sensitive proteins |
| Yang S. et al., 2015 | Resveratrol | Oxaliplatin | CRC cell culture (HCT-116, HT-29) and mouse xenograft CRC model | Synergistic effect of resveratrol and oxaliplatin in a miR-34c dependent manner | Up-regulation of miR-34c |
| Fulda and Debatin, 2004 | Resveratrol | 5-Fluorouracil | CRC cell culture (HCT-116) and other human cancer cell lines | Positive: Resveratrol sensitizes CRC cells for subsequent treatment with 5-Fu | Cell cycle arrest and apoptosis by downregulation of surviving, irrespective of p53 status |
| Hwang et al., 2007a | Resveratrol | Etoposide | CRC cell culture (HT-29) | Positive: Resveratrol chemosensitizes CRC cells for subsequent treatment with etoposide | inhibition of cell growth, increase of ROS generation, activation of AMPK, induction of apoptosis |
| Tolba and Abdel-Rahman, 2015 | Pterostilbene | 5-Fluorouracil | CRC cell culture (HCT-116, Caco-2) | Synergistic effect of pterostilbene on cytotoxic effects of 5-FU | Supression of Akt and ERK phosphorylation. Increase of FOXO-1 and p27kip1 levels |