Resveratrol as Chemosensitizer Agent: State of Art and Future Perspectives
Abstract
:1. Introduction
2. Natural Compounds as a Strategy for Chemosensitization
3. Mechanism of Action of Resveratrol in Cancer
4. Resveratrol as a Chemosensitizer Agent
4.1. Alkylating Agents
4.2. Platinum Compounds
4.3. Anthracyclines
4.4. Antimetabolites
4.5. Mitotic Inhibitors
4.6. Endocrine Therapy
5. Conclusions and Perspectives
Author Contributions
Funding
Conflicts of Interest
References
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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] |
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Cocetta, V.; Quagliariello, V.; Fiorica, F.; Berretta, M.; Montopoli, M. Resveratrol as Chemosensitizer Agent: State of Art and Future Perspectives. Int. J. Mol. Sci. 2021, 22, 2049. https://doi.org/10.3390/ijms22042049
Cocetta V, Quagliariello V, Fiorica F, Berretta M, Montopoli M. Resveratrol as Chemosensitizer Agent: State of Art and Future Perspectives. International Journal of Molecular Sciences. 2021; 22(4):2049. https://doi.org/10.3390/ijms22042049
Chicago/Turabian StyleCocetta, Veronica, Vincenzo Quagliariello, Francesco Fiorica, Massimiliano Berretta, and Monica Montopoli. 2021. "Resveratrol as Chemosensitizer Agent: State of Art and Future Perspectives" International Journal of Molecular Sciences 22, no. 4: 2049. https://doi.org/10.3390/ijms22042049
APA StyleCocetta, V., Quagliariello, V., Fiorica, F., Berretta, M., & Montopoli, M. (2021). Resveratrol as Chemosensitizer Agent: State of Art and Future Perspectives. International Journal of Molecular Sciences, 22(4), 2049. https://doi.org/10.3390/ijms22042049