Resveratrol and Resveratrol-Aspirin Hybrid Compounds as Potent Intestinal Anti-Inflammatory and Anti-Tumor Drugs

Salla, Mohamed; Pandya, Vrajesh; Bhullar, Khushwant S.; Kerek, Evan; Wong, Yoke Fuan; Losch, Robyn; Ou, Joe; Aldawsari, Fahad S.; Velázquez-Martínez, Carlos A.; Thiesen, Aducio; Dyck, Jason R.B.; Hubbard, Basil P.; Baksh, Shairaz

doi:10.3390/molecules25173849

Cited by 22 publications

(18 citation statements)

References 73 publications

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“…Interestingly, while COXs are important regulators of inflammation and angiogenesis, they are also implicated in carcinogenesis, as the overexpression of COX-2 has been reported as one of the causative factors for CRC development [ 74 ]. RSV and RSV-derived compounds, such as RSV-aspirin hybrid compounds, by targeting COX activity, are also considered potent intestinal anti-inflammatory and anti-tumor drugs [ 75 , 76 ].…”

Section: Discussionmentioning

confidence: 99%

A Micro-Immunotherapy Sequential Medicine MIM-seq Displays Immunomodulatory Effects on Human Macrophages and Anti-Tumor Properties towards In Vitro 2D and 3D Models of Colon Carcinoma and in an In Vivo Subcutaneous Xenograft Colon Carcinoma Model

Jacques¹,

Marchesi²,

Fiorentino³

et al. 2022

IJMS

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In this study, the immunomodulatory effects of a sequential micro-immunotherapy medicine, referred as MIM-seq, were appraised in human primary M1 and M2 macrophages, in which the secretion of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-12, IL-23, and tumor necrosis factor (TNF)-alpha, was inhibited. In addition, the potential anti-proliferative effects of MIM-seq on tumor cells was assessed in three models of colorectal cancer (CRC): an in vitro two-dimensions (2D) model of HCT-116 cells, an in vitro tri-dimensional (3D) model of spheroids, and an in vivo model of subcutaneous xenografted mice. In these models, MIM-seq displayed anti-proliferative effects when compared with the vehicle. In vivo, the tumor growth was slightly reduced in MIM-seq-treated animals. Moreover, MIM-seq could slightly reduce the growth of our spheroid models, especially under serum-deprivation. When MIM-seq was combined with two well-known anti-cancerogenic agents, either resveratrol or etoposide, MIM-seq could even further reduce the spheroid’s volume, pointing up the need to further assess whether MIM-seq could be beneficial for CRC patients as an adjuvant therapy. Altogether, these data suggest that MIM-seq could have anti-tumor properties against CRC and an immunomodulatory effect towards the mediators of inflammation, whose systemic dysregulation is considered to be a poor prognosis for patients.

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Section: Discussionmentioning

confidence: 99%

A Micro-Immunotherapy Sequential Medicine MIM-seq Displays Immunomodulatory Effects on Human Macrophages and Anti-Tumor Properties towards In Vitro 2D and 3D Models of Colon Carcinoma and in an In Vivo Subcutaneous Xenograft Colon Carcinoma Model

Jacques¹,

Marchesi²,

Fiorentino³

et al. 2022

IJMS

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“…Moreover, resveratrol diminished the inflammatory responses induced by lipopolysaccharide in SW480 and Caco-2 colon cancer cell lines by reducing the activation, expression, and production of inducible NO synthase (iNOS), mRNA, TLR4, and NF-kB (113). Furthermore, resveratrol suppressed the activity of COX, AMP-activated protein kinase (AMPK), PI3K/Akt/NF-kB pathway, DNA methyltransferase, and CYP1A1 in acute myeloid leukemia (AML), colon, and pancreatic cancer cells (114)(115)(116). In similar studies, resveratrol exerted substantial antineoplastic activity against multiple cancer cell lines, including melanoma (117), lung (118,119), glioblastoma (120), head, neck (109), hepatocellular (121), colorectal (122), and breast (123) cancer cells by interfering with dicer-like 1 (DCL1)/translationally controlled tumor protein (TCTP), Akt/ NF-kB, retinoblastoma protein (pRB), VEGF, AMPK, and p21 Waf1/Cip1 signaling pathways.…”

Section: Phenolic Compoundsmentioning

confidence: 99%

Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy

et al. 2022

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BackgroundTumors often progress to a more aggressive phenotype to resist drugs. Multiple dysregulated pathways are behind this tumor behavior which is known as cancer chemoresistance. Thus, there is an emerging need to discover pivotal signaling pathways involved in the resistance to chemotherapeutic agents and cancer immunotherapy. Reports indicate the critical role of the toll-like receptor (TLR)/nuclear factor-κB (NF-κB)/Nod-like receptor pyrin domain-containing (NLRP) pathway in cancer initiation, progression, and development. Therefore, targeting TLR/NF-κB/NLRP signaling is a promising strategy to augment cancer chemotherapy and immunotherapy and to combat chemoresistance. Considering the potential of phytochemicals in the regulation of multiple dysregulated pathways during cancer initiation, promotion, and progression, such compounds could be suitable candidates against cancer chemoresistance.ObjectivesThis is the first comprehensive and systematic review regarding the role of phytochemicals in the mitigation of chemoresistance by regulating the TLR/NF-κB/NLRP signaling pathway in chemotherapy and immunotherapy.MethodsA comprehensive and systematic review was designed based on Web of Science, PubMed, Scopus, and Cochrane electronic databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to include papers on TLR/NF-κB/NLRP and chemotherapy/immunotherapy/chemoresistance by phytochemicals.ResultsPhytochemicals are promising multi-targeting candidates against the TLR/NF-κB/NLRP signaling pathway and interconnected mediators. Employing phenolic compounds, alkaloids, terpenoids, and sulfur compounds could be a promising strategy for managing cancer chemoresistance through the modulation of the TLR/NF-κB/NLRP signaling pathway. Novel delivery systems of phytochemicals in cancer chemotherapy/immunotherapy are also highlighted.ConclusionTargeting TLR/NF-κB/NLRP signaling with bioactive phytocompounds reverses chemoresistance and improves the outcome for chemotherapy and immunotherapy in both preclinical and clinical stages.

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“…The two bioactive molecules were joined by means of a cleavable amide or ester moiety (an example of a fused drug) with the aim of enhancing the bioavailability of the single On this basis, and in the attempt to improve the bioavailability and reduce the catabolism of this type of hybrid, Salla et al more recently synthesized Res-aspirin hybrid compounds, which showed antiproliferative and anti-inflammatory activities both in vitro (HCT-116 cells) and in vivo (reduction of the intestinal tumor burden in a xenograft murine model with HCT-116 cells). Additionally, the authors provided details on how these hybrids inhibit the activation of several tumor signaling factors, such as nuclear factor-κB (NF-κB), sirtuin, and AMP-activated protein kinase (AMPK) [55].…”

Section: Hybrid Compounds Containing Curcumin and Resveratrolmentioning

confidence: 99%

Natural Product-Based Hybrids as Potential Candidates for the Treatment of Cancer: Focus on Curcumin and Resveratrol

et al. 2021

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One of the main current strategies for cancer treatment is represented by combination chemotherapy. More recently, this strategy shifted to the “hybrid strategy”, namely the designing of a new molecular entity containing two or more biologically active molecules and having superior features compared with the individual components. Moreover, the term “hybrid” has further extended to innovative drug delivery systems based on biocompatible nanomaterials and able to deliver one or more drugs to specific tissues or cells. At the same time, there is an increased interest in plant-derived polyphenols used as antitumoral drugs. The present review reports the most recent and intriguing research advances in the development of hybrids based on the polyphenols curcumin and resveratrol, which are known to act as multifunctional agents. We focused on two issues that are particularly interesting for the innovative chemical strategy involved in their development. On one hand, the pharmacophoric groups of these compounds have been used for the synthesis of new hybrid molecules. On the other hand, these polyphenols have been introduced into hybrid nanomaterials based on gold nanoparticles, which have many potential applications for both drug delivery and theranostics in chemotherapy.

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Resveratrol and Resveratrol-Aspirin Hybrid Compounds as Potent Intestinal Anti-Inflammatory and Anti-Tumor Drugs

Cited by 22 publications

References 73 publications

A Micro-Immunotherapy Sequential Medicine MIM-seq Displays Immunomodulatory Effects on Human Macrophages and Anti-Tumor Properties towards In Vitro 2D and 3D Models of Colon Carcinoma and in an In Vivo Subcutaneous Xenograft Colon Carcinoma Model

A Micro-Immunotherapy Sequential Medicine MIM-seq Displays Immunomodulatory Effects on Human Macrophages and Anti-Tumor Properties towards In Vitro 2D and 3D Models of Colon Carcinoma and in an In Vivo Subcutaneous Xenograft Colon Carcinoma Model

Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy

Natural Product-Based Hybrids as Potential Candidates for the Treatment of Cancer: Focus on Curcumin and Resveratrol

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