Curcumin: a therapeutic strategy in cancers by inhibiting the canonical WNT/β-catenin pathway

Journal of Experimental & Clinical Cancer Research, Journal Year: 2019, Volume and Issue: 38(1)

Published: July 22, 2019

Numerous studies have presented that curcumin could a positive effect in the prevention of cancer and then tumor therapy. Several hypotheses highlighted decreases growth invasion by acting on both chronic inflammation oxidative stress. This review focuses interest use therapy WNT/β-catenin pathway to repress In process, one major signaling pathways involved is pathway, which appears be upregulated. Curcumin administration participates downregulation thus, through this action, control. act as PPARγ agonists. The an opposed manner. Chronic inflammation, stress circadian clock disruption are common co-substantial pathological processes accompanying promoting cancers. Circadian related upregulation By stimulating expression, can control clocks regulation many key genes. treatment would thus appear interesting therapeutic strategy, acts their role regulating activity levels.

Language: Английский

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Neurobiology of Cancer: The Role of β-Adrenergic Receptor Signaling in Various Tumor Environments

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(21), P. 7958 - 7958

Published: Oct. 26, 2020

The development and progression of cancer depends on both tumor micro- macroenvironments. In addition, psychosocial spiritual "environments" might also affect cancer. It has been found that the nervous system, via neural humoral pathways, significantly modulates processes related to at level system mediates effects noetic factors Importantly, data accumulated in last two decades have clearly shown initiation, progression, metastases are mediated by sympathoadrenal mainly β-adrenergic receptor signaling. Here, we provide a new complex view role signaling within macroenvironments as well mediating environments. describe potential preventive therapeutic implications.

Language: Английский

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Circadian Regulator CLOCK Drives Immunosuppression in Glioblastoma

Cancer Immunology Research, Journal Year: 2022, Volume and Issue: 10(6), P. 770 - 784

Published: April 12, 2022

Abstract The symbiotic interactions between cancer stem cells and the tumor microenvironment (TME) are critical for progression. However, molecular mechanism underlying this symbiosis in glioblastoma (GBM) remains enigmatic. Here, we show that circadian locomotor output cycles kaput (CLOCK) its heterodimeric partner brain muscle ARNT-like 1 (BMAL1) glioma (GSC) drive immunosuppression GBM. Integrated analyses of data from transcriptome profiling, single-cell RNA sequencing, TCGA datasets, coupled with functional studies, identified legumain (LGMN) as a direct transcriptional target CLOCK–BMAL1 complex GSCs. Moreover, CLOCK-directed olfactomedin-like 3 (OLFML3) upregulates LGMN GSCs via hypoxia-inducible factor 1-alpha (HIF1α) signaling. Consequently, promotes microglial infiltration into GBM TME upregulating CD162 polarizes infiltrating microglia toward an immune-suppressive phenotype. In mouse models, inhibition CLOCK–OLFML3–HIF1α–LGMN–CD162 axis reduces intratumoral microglia, increases CD8+ T-cell infiltration, activation, cytotoxicity, synergizes anti–programmed cell death protein (anti–PD-1 therapy). human GBM, CLOCK-regulated signaling correlates positively abundance poor prognosis. Together, these findings uncover CLOCK–OLFML3–HIF1α–LGMN switch controls biology immunosuppression, thus revealing potential new therapeutic targets patients

Language: Английский

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The Circadian Clock Gene, Bmal1, Regulates Intestinal Stem Cell Signaling and Represses Tumor Initiation

Cellular and Molecular Gastroenterology and Hepatology, Journal Year: 2021, Volume and Issue: 12(5), P. 1847 - 1872.e0

Published: Jan. 1, 2021

Circadian rhythms are daily physiological oscillations driven by the circadian clock: a 24-hour transcriptional timekeeper that regulates hormones, inflammation, and metabolism. known to be important for health, but whether their loss contributes colorectal cancer is not known. We tested nonredundant clock gene Bmal1 in intestinal homeostasis tumorigenesis, using Apcmin model of cancer.Bmal1 mutant, epithelium-conditional photoperiod (day/night cycle) disrupted mice bearing allele were assessed tumorigenesis. Tumors normal nontransformed tissue characterized. Intestinal organoids transcription RNA sequencing, vivo organoid assays used test Bmal1-dependent proliferation self-renewal.Loss or increases tumor initiation. In epithelium transcripts involved regeneration stem cell signaling. have no self-autonomous function only weak vivo. clock-disrupted tumors show high Yes-associated protein 1 (Hippo signaling) activity low Wnt (Wingless Int-1) activity. self-renewal 1-dependent manner.Bmal1 pathways, including Hippo signaling, potentiates Transcript profiling: GEO accession number: GSE157357.

Language: Английский

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In vivo flow cytometry reveals a circadian rhythm of circulating tumor cells

Light Science & Applications, Journal Year: 2021, Volume and Issue: 10(1)

Published: May 28, 2021

Abstract Circulating tumor cells (CTCs) is an established biomarker of cancer metastasis. The circulation dynamics CTCs are important for understanding the mechanisms underlying cell dissemination. Although studies have revealed that circadian rhythm may disrupt growth tumors, it generally unclear whether controls release CTCs. In clinical examinations, current in vitro methods detecting blood samples based on a fundamental assumption CTC counts peripheral do not change significantly over time, which being challenged by recent studies. Since practical to draw from patients repeatedly, feasible strategy investigate monitor them vivo detection methods. Fluorescence flow cytometry (IVFC) powerful optical technique able detect fluorescent circulating directly living animals noninvasive manner long period time. this study, we applied fluorescence IVFC noninvasively orthotopic mouse model human prostate cancer. We observed exhibited stochastic bursts progression. probability bursting activity was higher at early stages than late stages. longitudinally monitored 24-h period, and our results striking daily oscillations peaked onset night (active phase rodents), suggesting might be regulated rhythm.

Language: Английский

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