MyD88 in DNA Repair and Cancer Cell Resistance to Genotoxic Drugs

Kfoury, Alain; Corf, Katy Le; Sabeh, Rana El; Journeaux, Alexandra; Badran, Bassam; Hussein, Nader; Lebecque, Serge; Manié, Serge N.; Renno, Toufic; Coste, Isabelle

doi:10.1093/jnci/djt120

Cited by 30 publications

(28 citation statements)

References 17 publications

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“…In accordance with the data obtained by Kfoury et al, MyD88 inhibition may lead to defective excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1)-dependent DNA repair and to accumulation of DNA damage (29, 30). In addition, abrogation of MyD88 gene expression sensitizes cancer cells to genotoxic agents such as platinum salts in vitro and in vivo (29, 30).…”

supporting

confidence: 90%

Pattern Recognition Receptors and DNA Repair: Starting to Put a Jigsaw Puzzle Together

et al. 2014

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supporting

confidence: 90%

Pattern Recognition Receptors and DNA Repair: Starting to Put a Jigsaw Puzzle Together

et al. 2014

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“…HEK-293-Blue TLR cell lines were serum starved for 6 h and then treated with 25 M L-C14 carnitine or appropriate positive controls: HKLM (heat-killed listeria monocytogenes) at 10 8 cells/ml for HEK-293-hTLR2, LPS K12 (100 ng/ml) for HEK-293-hTLR4, and flagellin (1 g/ml) for HEK-293-hTLR5, CL097 (1 g/ml) for HEK-293-TLR7 and HEK-293-TLR8, CpG ODN 2006 (1 g/ml) for HEK-293-TLR9, and TNF␣ (1 g/ml). express MyD88 (6). Secretion of IL-8 was significantly increased from HCT-116 cells treated with L-C14 carnitine, indicating that L-C14 carnitine-induced HCT-116 cell IL-8 expression is mediated through signaling pathways other than TLR2 or TLR4.…”

Section: Discussionmentioning

confidence: 93%

Acylcarnitines activate proinflammatory signaling pathways

Rutkowsky

Knotts

Ono‐Moore

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

251

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Incomplete β-oxidation of fatty acids in mitochondria is a feature of insulin resistance and type 2 diabetes mellitus (T2DM). Previous studies revealed that plasma concentrations of medium- and long-chain acylcarnitines (by-products of incomplete β-oxidation) are elevated in T2DM and insulin resistance. In a previous study, we reported that mixed d,l isomers of C12- or C14-carnitine induced an NF-κB-luciferase reporter gene in RAW 264.7 cells, suggesting potential activation of proinflammatory pathways. Here, we determined whether the physiologically relevant l-acylcarnitines activate classical proinflammatory signaling pathways and if these outcomes involve pattern recognition receptor (PRR)-associated pathways. Acylcarnitines induced the expression of cyclooxygenase-2 in a chain length-dependent manner in RAW 264.7 cells. l-C14 carnitine (5–25 μM), used as a representative acylcarnitine, stimulated the expression and secretion of proinflammatory cytokines in a dose-dependent manner. Furthermore, l-C14 carnitine induced phosphorylation of JNK and ERK, common downstream components of many proinflammatory signaling pathways including PRRs. Knockdown of MyD88, a key cofactor in PRR signaling and inflammation, blunted the proinflammatory effects of acylcarnitine. While these results point to potential involvement of PRRs, l-C14 carnitine promoted IL-8 secretion from human epithelial cells (HCT-116) lacking Toll-like receptors (TLR)2 and -4, and did not activate reporter constructs in TLR overexpression cell models. Thus, acylcarnitines have the potential to activate inflammation, but the specific molecular and tissue target(s) involved remain to be identified.

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“…Myeloid differentiation primary response 88 (MyD88) is responsible for cell survival, DNA repair, and maintenance of stemness, thereby contributing to therapeutic resistance in cancer [ 275 , 276 ]. It was disclosed that ursolic acid reverses paclitaxel resistance by downregulating MyD88 levels in lung and breast cancer [ 85 , 146 ].…”

Section: Tumor-suppressive Mirnas Induced By Phytochemicals Currenmentioning

confidence: 99%

Participation of MicroRNAs in the Treatment of Cancer with Phytochemicals

et al. 2020

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Cancer is a global health concern and one of the main causes of disease-related death. Even with considerable progress in investigations on cancer therapy, effective anti-cancer agents and regimens have thus far been insufficient. There has been compelling evidence that natural phytochemicals and their derivatives have potent anti-cancer activities. Plant-based anti-cancer agents, such as etoposide, irinotecan, paclitaxel, and vincristine, are currently being applied in medical treatments for patients with cancer. Further, the efficacy of plenty of phytochemicals has been evaluated to discover a promising candidate for cancer therapy. For developing more effective cancer therapy, it is required to apprehend the molecular mechanism deployed by natural compounds. MicroRNAs (miRNAs) have been realized to play a pivotal role in regulating cellular signaling pathways, affecting the efficacy of therapeutic agents in cancer. This review presents a feature of phytochemicals with anti-cancer activity, focusing mainly on the relationship between phytochemicals and miRNAs, with insights into the role of miRNAs as the mediators and the regulators of anti-cancer effects of phytochemicals.

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MyD88 in DNA Repair and Cancer Cell Resistance to Genotoxic Drugs

Abstract: Collectively, these results indicate a novel and original link between inflammation, DNA repair, and cancer, and provide further rationale for MyD88 as a potential therapeutic target in Ras-dependent cancers, in the context of concomitant genotoxic chemotherapy.

Cited by 30 publications

References 17 publications

Pattern Recognition Receptors and DNA Repair: Starting to Put a Jigsaw Puzzle Together

Pattern Recognition Receptors and DNA Repair: Starting to Put a Jigsaw Puzzle Together

Acylcarnitines activate proinflammatory signaling pathways

Participation of MicroRNAs in the Treatment of Cancer with Phytochemicals

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