Regulation of Cell Signaling Pathways and miRNAs by Resveratrol in Different Cancers

Abstract

Genomic and proteomic studies have helped improve our understanding of the underlying mechanism(s) of cancer development and progression. Mutations, overexpressed oncogenes, inactivated/downregulated tumor suppressors, loss of apoptosis, and dysregulated signal transduction cascades are some of the well-studied areas of research. Resveratrol has gained considerable attention in the last two decades because of its pleiotropic anticancer activities. In this review, we have summarized the regulation of WNT, SHH (sonic hedgehog)/GLI (glioma-associated oncogene homolog), TGFβ1 (transforming growth factor beta 1)/SMAD, NOTCH, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), STAT (signal transducer and activator of transcription), and microRNAs by resveratrol in different cancers. The importance of these signaling pathways in cancer progression, along with their modulation by resveratrol, is discussed. Further, we also evaluate the mechanisms and implications of the downregulation of oncogenic miRNAs and the upregulation of tumor suppressor miRNAs by resveratrol, both of which also define its ability to inhibit tumor growth and metastasis. It is envisioned that designing effective clinical trials will be helpful for the identification of resveratrol responders and non-responders and the elucidation of how this phytochemical can be combined with current therapeutic options to improve their clinical efficacy and reduce off-target effects.

Resveratrol inhibits Src tyrosine kinase, STAT3, and Wnt signaling pathway in collagen induced arthritis model

“…Previous studies have shown that resveratrol has several anti‐inflammatory effects . In the CIA model, we found that resveratrol inhibited Src tyrosine kinase, STAT3, and Wnt signaling pathways, resveratrol‐ameliorated inflammatory arthritis.…”

“…Limagne et al have reported that resveratrol inhibits the IL‐6 and IL‐1β induced STAT3 activation in the cell culture of macrophages. It is known that resveratrol increases negative regulators of STAT signaling [SH2 domain‐containing tyrosine phosphatase (SHP‐2), protein inhibitor of activated STAT (PIAS), and protein tyrosine phosphatases (PTP)], and thus, it inhibits the activation of STAT . In our study, resveratrol decreased the mRNA expression of STAT3.…”

Anticancer potential of naturally occurring immunoepigenetic modulators: A promising avenue?

“…Accordingly, resveratrol‐treated SIRT1 null mice develop tumors at normal rates . In addition, there is a large body of evidence demonstrating that resveratrol suppresses the expression of various oncogenic miRNAs and upregulates tumor‐suppressor miRNAs in various cancer models …”

“…14 In addition, there is a large body of evidence demonstrating that resveratrol suppresses the expression of various oncogenic miRNAs and upregulates tumor-suppressor miRNAs in various cancer models. 75,83 The antitumor immunomodulatory properties of resveratrol have been highlighted in several studies and encompass the inhibition of immunosuppressive mechanisms in the TME and immune-enhancing properties. Resveratrol reportedly diminished Treg counts and functions ex vivo and in vivo, which are associated with the downregulation of TGF-β secretion from the spleen of EG7 lymphoma cell-induced and CT26 colon carcinoma cell-induced, tumor-bearing mice.…”

Bioactive Phenolics and Polyphenols: Current Advances and Future Trends

“…The Special Issue included seven review papers that describe the current status of phenolic compounds, covering general aspects of their bioactivity for the suppression of chronic diseases [ 1 ], as well as the bioactivity of specific group of phenolics such as the stilbenoids [ 22 , 23 ], ellagitannins, and anthocyanins [ 24 ]. In addition, the health-promoting properties of phenolics present in lentils [ 25 ] and dry common beans [ 26 ] were also reviewed.…”