Table 1.
Summary of the current literature concerning the chemosensitizing effect of resveratrol combined with conventional anticancer drugs.
| Drug Class | Drug | Cancer Model | Effect in Combination with Resveratrol | References |
|---|---|---|---|---|
| Alkylating agents | Temozolomide | SHG44 GBM cell line In vivo xenograft mouse models |
Additive effect by ROS-dependent AMPK-TSC-mTOR signaling pathway Reduction of tumor growth |
[53] |
| GBM-initiating cells (GICs) | Activation of the DNA double strands pATM/pART/p53 pathway | [54] | ||
| GBM cells | By downregulating MGMT via the NF-KB dependent pathway and via the repression of the activated Wnt signaling pathway | [56,57] | ||
| Glioma cells | Mitotic catastrophe and senescence | [58] | ||
| Platinum compounds |
Cisplatin | Non-small lung cancer cells (NSCLC) H838 and H520 | Depolarization of MMP and apoptosis | [65] |
| A549 lung carcinoma cells | Decreases the phosphorylation of AKT thus inducing autophagy | [67] | ||
| Hepatoma cells C3A and SMCC7721 |
Reduction of transporter ASCT2 imbalance in the redox homeostasis |
[69] | ||
| A2780, OVCAR-3 CaOv-4 |
Proapoptotic effect | [70,71,72,73] | ||
| EAC tumor-bearing mice | Activation of proapoptotic family members | [77] | ||
| Melanoma models | Upregulation of connexin 43 expression | [78] | ||
| Oxaliplatin | Colon cancer cell line | Inhibition of cell growth | [74] | |
| Colon cancer cell line Caco2 | Interfering with caspase-3-activation, PARP cleavage, and depolarization of mitochondrial membrane potential | [76] | ||
| HCT116 cells | Reestablishment of surviving protein expression | [75] | ||
| Anthracyclines | Doxorubicin (Adriamycin) | MDA-MB-231 and MCF-7/Adr breast cancer cells MCF-7/Adr cell xenograft model |
Decreases the expression of MDR1 and MRP1; decreases P-gp ATPase activity Reduces tumor volume and expression levels of MDR1 and MRP1 |
[81] |
| MCF-7 and MDA-MB-231 cell lines Ehrlich ascitic carcinoma cells-bearing mice |
Growth inhibition, decreased clonogenic potential, inhibition of inflammatory response, induction of apoptosis. Reduced tumor volume, increased lifespan |
[82] | ||
| SGC7901 gastric cancer and SGC7901/DOX in vivo xenograft tumor model | Suppressing ETM via modulation of PTEN/Akt signaling pathway | [84] | ||
| MCF7/Adr breast cancer cells | Regulation of SIRT1/ β-catenin pathway | [85] | ||
| MCF-7/Adr breast cancer cells | Targeting miR-122-5p, thus regulating apoptosis-inhibitory proteins Bcl-2 and CDKs | [86] | ||
| Spheroids of PANC-1 pancreatic cells | Reduced P-glycoprotein mediated efflux of the drug | [87] | ||
| HCT116 colon cancer cell lines | Increased expression of Bax gene and blocked the efflux activity of p-gp | [88] | ||
| Caco-2 colorectal and CEM/ADR5000 T lymphoblastoid cell line |
Inhibition of the ABC transporters, metabolic enzyme GST and CYP3A4 activity | [89] | ||
| Antimetabolites | 5-Fluorouracil | Colorectal cancer cells | Inhibiting pAkt signaling pathway Reduction of TNF-β-induced epithelial-mesenchymal transition and downregulation of NF-KB |
[94] [98,99] |
| Colorectal cancer cell lines | Imbalance in redox homeostasis linked to inhibition of Akt and STAT3 levels | [95] | ||
| B16 murine melanoma cells B16-tumors model in mice |
Regulation of levels of AMPK, COX-2, VASP and VEGF Reduces tumor growth |
[96] | ||
| Murine model of liver | Reduces tumor growth | [97] | ||
| Gemcitabine | Advanced pancreatic cancer (PC) | Downregulation of SREBP1 | [101] | |
| PaCa xenografts in nude mice | Reduces tumor growth | [102] | ||
| Pancreatic cancer cells | ROS accumulation, activation of Nrf-2 signaling, suppression of NAF-1 | [103] | ||
| Pancreatic cancer cells | Downregulation of YAP | [104] | ||
| Pancreatic cancer cells and in vivo model | Downregulation of VEGF-B and GSK3β | [105] | ||
| Human bladder cancer cell line | Modulation of ABCC2, DCK, TK1 and TK2 function and increased PARP cleavage and apoptosis | [106] | ||
| Mitotic Inhibitors |
Docetaxel | HER-2-overexpressing SK-BR-3 breast cancer cells | Blocks the enhancement and activation of HER-2, in addition to blocking AKT pathway | [108] |
| Paclitaxel | MDA-MB-231 breast cancer cell line | Induction of cell senescence and apoptosis | [109] | |
| Paclitaxel-resistant non-Hodgkin’s lymphoma and multiple myeloma | Decreases Bcl-x, upregulates Bax and Apaf-1 expression. | [110] | ||
| MCF-7 and T47D ERα positive breast cancer cells | Decreases NGB levels, via interference with E2/Erα pathway | [111] | ||
| DBTRG glioblastoma cell lines | Stimulation and activation of the oxidative sensitive TRPM2 channel | [112] | ||
| Endocrine therapy |
Tamoxifen | MCF-7 Tamoxifen-resistant cancer cells | Transcriptional inhibition of ERα via blockade of cell cycle, activation of p38 MAPK/CK2 signaling and induction of p53 | [119] |
| 4-hydroxy -tamoxifen (4-OHT) |
MCF-7-TR breast cancer cells | Inhibition of ER transcription via p38 MAPK/casein kinase II signaling, p53, binding with the transcription nuclear factor Y (NF-Y) to the ER proximal promoter | [119] | |
| Raloxifene | MCF7 cells estrogen-receptor positive | Increases the Bcl2/Bax ratio and expression of p53 and caspases 3,8 | [121] | |
| Bicalutamide | Prostate cancer | Via downregulation of AKT signaling pathway, suppresses CXCR4 expression | [123,125] |