Resveratrol inhibits STAT3 signaling pathway through the induction of SOCS-1: Role in apoptosis induction and radiosensitization in head and neck tumor cells

Baek, Seung Ho; Ko, Jeong‐Hyeon; Lee, Hanwool; Jung, Jinhong; Kong, Moonkyoo; Lee, Jung-woo; Lee, Junhee; Chinnathambi, Arunachalam; Zayed, Mohamed E.; Alharbi, Sulaiman Ali; Lee, Seok‐Geun; Shim, Bum Sang; Sethi, Gautam; Kim, Sung Hoon; Yang, Woong Mο; Um, Jae‐Young; Ahn, Kwang Seok

doi:10.1016/j.phymed.2016.02.011

Cited by 155 publications

(103 citation statements)

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“…A particular subset of macrophages, named tumor-associated macrophages (TAMs), are activated by cancer cells and promote the production of inflammatory cytokines through a STAT3 pathway. Resveratrol is able to decrease STAT3 activation in cancer [152]. In addition, resveratrol modulates the PI3K pathway in cancer cells, which downregulates CD8+ cytotoxic T cell activity.…”

Section: Resveratrol and Cancer Evidencementioning

confidence: 99%

Resveratrol in Cancer Patients: From Bench to Bedside

Berretta

Bignucolo

Francia

et al. 2020

IJMS

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Resveratrol (3,5, is a natural phytoalexin that accumulates in several vegetables and fruits like nuts, grapes, apples, red fruits, black olives, capers, red rice as well as red wines. Being both an extremely reactive molecule and capable to interact with cytoplasmic and nuclear proteins in human cells, resveratrol has been studied over the years as complementary and alternative medicine (CAM) for the therapy of cancer, metabolic and cardiovascular diseases like myocardial ischemia, myocarditis, cardiac hypertrophy and heart failure. This review will describe the main biological targets, cardiovascular outcomes, physico-chemical and pharmacokinetic properties of resveratrol in preclinical and clinical models implementing its potential use in cancer patients.properties of resveratrol are, however, marked by a pharmacokinetic profile and by an unfavorable oral bioavailability, which requires a thorough analysis. To date, to the best of our knowledge, scientific papers and reviews summarizing multiple characteristics of resveratrol, its pharmacokinetic, pharmacodynamic profiles and potential drug interaction in oncology are lacking in literature. Therefore, this review aimed to describe the potential use of resveratrol in cancer management presenting the main biochemical pathways involved, issues and potential uses in cancer patients. Moreover, the involvement of resveratrol in cardioncology, its potential use for risk reduction of myocardial ischemia, myocarditis, cardiac hypertrophy as well as heart failure are also discussed. To endorse this review, we made a comprehensive search on PubMed, Web of Science and SciFinder. The search terms were "resveratrol" combined with "cardioncology" or "cancer" or "drug-food" or "cardiology" or "pharmacokinetic" or "pharmacodynamic". Physico-Chemical and Pharmacokinetic Properties of ResveratrolResveratrol is a low molecular weight phyto-polyphenol of 228 Da that appears as an off-white powder with lipophilic properties (octanol/water partition coefficient, log Kow = 3.1). Its melting point is between 253 and 255 • C, and its solubility in water is very low (3 mg/100 mL) [8]. The ethylene bridge due to a limited degree of freedom generates two geometric isomers: cis-resveratrol and trans-resveratrol ( Figure 1) [5]. These isoforms co-exist in resveratrol extracts even if a greater biological activity and stability are attributed to trans-resveratrol. Comparing to the geometric isomers, the nearly planar structure of trans-resveratrol is less flexible than the non-planar structure of cis-resveratrol, but it possesses a lower repulsive energy that ensures it, albeit small, higher stability. Isomerization of trans-resveratrol to cis-resveratrol occurs via molecule breakdown when trans-resveratrol is exposed to UV radiation at a wavelength of 254 or 366 nm, to high pH conditions or in plants during fermentation processes [5,9]. In analyzing some physical-chemical aspects of resveratrol, Zupancic et al. showed how trans-resveratrol is rapidly degradable in high-pH solutions. In par...

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Section: Resveratrol and Cancer Evidencementioning

confidence: 99%

Resveratrol in Cancer Patients: From Bench to Bedside

Berretta

Bignucolo

Francia

et al. 2020

IJMS

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“…Among dietary polyphenols, resveratrol (3,4’,5-trihydroxy-trans-stilbene), found in the skin of grapes, blueberries, raspberries and mulberries [9], is known to be effective against bacterial and fungal infections [10, 11], cardiovascular diseases [12], metabolic diseases [13], and cancer [14–16]. Resveratrol has also been reported to show anti-inflammatory effects [17], inhibit lipid peroxidation [18], and activate free radical scavenging [19], further supporting the evidence in the favor of the antioxidant activity of resveratrol.…”

Section: Introductionmentioning

confidence: 99%

Trans-scirpusin A showed antitumor effects via autophagy activation and apoptosis induction of colorectal cancer cells

et al. 2017

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Trans-Scirpusin A (TSA) is a resveratrol oligomer found in Borassus flabellifer L. We found that TSA inhibited the growth of colorectal cancer Her2/CT26 cells in vivo in mice. Although some cytotoxic T lymphocytes (CTLs) were induced against the tumor-associated antigen Her2, TSA treatment did not significantly increase the level of Her2-specific CTL response compared to that with vehicle treatment. However, there was a significant increase in the level of TNF-α mRNA in tumor tissue and Her2-specific Ab (antibody) production. More importantly, we found that TSA overcomes the tumor-associated immunosuppressive microenvironment by reducing the number of CD25+FoxP3+ regulatory T cells and myeloid-derived suppressor cells (MDSCs). We detected the induction of autophagy in TSA-treated Her2/CT26 cells, based on the increased level of the mammalian autophagy protein LC3 puncta, and increased conversion of LC3-I to LC3-II. Further, TSA induced 5' AMP-activated protein kinase (p-AMPK) (T172) and inhibited mammalian target of rapamycin complex 1 (mTORC1) activity as estimated by phosphorylated ribosomal protein S6 kinase beta-1 (p-p70S6K) levels, thereby suggesting that TSA-mediated AMPK activation and inhibition of mTORC1 pathway might be associated with autophagy induction. TSA also induced apoptosis of Her2/CT26 cells, as inferred by the increased sub-G1 mitotic phases in these cells, Annexin V/PI-double positive results, and TUNEL-positive cells. Finally, we found that the combined treatment of mice with docetaxel and TSA successfully inhibited tumor growth to a greater extent than docetaxel alone. Therefore, we propose the use of TSA for supplementary anticancer therapy to support anti-neoplastic drugs, such as docetaxel, by inducing apoptosis in cancer cells and resulting in the induction of neighborhood anti-cancer immunity.

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“…Real‐time cell analysis (RTCA) of invasion was monitored in the xCELLigence DP instrument (Roche Diagnostics, Mannheim, Germany) as described earlier (Baek et al, ). Cell index was measured every 15 min for up to 30 hr with the RTCA software (Version 1.2, Roche Diagnostics).…”

Section: Methodsmentioning

confidence: 99%

Theacrine attenuates epithelial mesenchymal transition in human breast cancer MDA‐MB‐231 cells

Yang

Baek

et al. 2019

Phytotherapy Research

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Theacrine, a purine alkaloid structurally similar to caffeine, has recently become of interest as a potential therapeutic compound. Here, we investigated the antimetastatic potential of theacrine on human breast cancer MDA‐MB‐231 cells. We observed that theacrine can reverse epithelial‐to‐mesenchymal transition (EMT), which resulted in a decrease in the levels of mesenchymal markers (Fibronectin, Vimentin, N‐cadherin, Twist, and Snail) and an increase in the levels of epithelial markers (Occludin and E‐cadherin) in the cells. Additionally, theacrine attenuates TGF‐β‐induced EMT, cell adhesion, migration, and invasion in MDA‐MB‐231 cells. Overall, our results suggest that theacrine may inhibit the breast cancer cell metastasis by reversing the EMT process.

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Resveratrol inhibits STAT3 signaling pathway through the induction of SOCS-1: Role in apoptosis induction and radiosensitization in head and neck tumor cells

Cited by 155 publications

References 58 publications

Resveratrol in Cancer Patients: From Bench to Bedside

Resveratrol in Cancer Patients: From Bench to Bedside

Trans-scirpusin A showed antitumor effects via autophagy activation and apoptosis induction of colorectal cancer cells

Theacrine attenuates epithelial mesenchymal transition in human breast cancer MDA‐MB‐231 cells

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