Early LC3 lipidation induced by d -limonene does not rely on mTOR inhibition, ERK activation and ROS production and it is associated with reduced clonogenic capacity of SH-SY5Y neuroblastoma cells

Berliocchi, Laura; Chiappini, Carlotta; Adornetto, Annagrazia; Gentile, Debora; Cerri, Silvia; Russo, Rossella; Bagetta, Giacinto; Corasaniti, Maria Tiziana

doi:10.1016/j.phymed.2018.01.005

Cited by 23 publications

(23 citation statements)

References 23 publications

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“…The function of the four ARGs that associated bad survival of NB in our study has been reported as follows: EIF4EBP1 is a downstream target of mTOR signaling pathway and could inhibit autophagy initiation (42,43); WDR45B was found to play an essential role in maintaining neural autophagy and neural homeostasis (44); SPNS1 was found to play an important role in orchestrating autolysosomal biogenesis and is critically linked to developmental senescence and survival (45); TM9SF1 was found to play important roles in inducing autophagy (46). Except for GABARAPL1, the roles of the other eight ARGs in NB genesis and progression have not been reported.…”

Section: Discussionmentioning

confidence: 72%

Comparison of Stage 4 and Stage 4s Neuroblastoma Identifies Autophagy-Related Gene and LncRNA Signatures Associated With Prognosis

Meng

Fang

et al. 2020

Front. Oncol.

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Background: The spontaneous regression of neuroblastoma (NB) is most prevalent and well-documented in stage 4s NB patients. However, whether autophagy plays roles in the spontaneous regression of NB is unknown. Objective: This study aimed to identify autophagy-related genes (ARGs) and autophagy-related long non-coding RNAs (lncRNAs) differentially expressed in stage 4 and stage 4s NB and to build prognostic risk signatures on the basis of the ARGs and autophagy-related lncRNAs. Methods: One RNA-sequence (RNA-Seq) dataset (TARGET NBL, n = 153) was utilized as discovery cohort, and two microarray datasets (n = 498 and n = 223) were used as validation cohorts. Differentially expressed ARGs were identified by comparing stage 4s and stage 4 NB samples. An ARG signature risk score and an autophagy-related lncRNA signature risk score were constructed. The receiver operating characteristic (ROC) curve analyses were used to evaluate the survival prediction ability of the two signatures. Gene function annotation and Gene Set Enrichment Analysis (GSEA) were performed to clarify the autophagic biological processes enriched in different risk groups. Results: Nine ARGs were integrated into the ARG signature. Patients in the high-risk group of the ARG signature had significantly poorer overall survival (OS) than patients in the low-risk group. The ROC curves analyses revealed that the ARG signature performed very well in predicting OS [5-year area under the curve (AUC) = 0.81]. Seven autophagy-related lncRNAs were integrated into the autophagy-related lncRNA signature. Patients in the high-risk group of the lncRNA signature had significantly poorer OS than patients in the low-risk group. The ROC curve analyses also revealed that the lncRNA signature performed well in predicting OS (5-year AUC = 0.77). Both the ARG signature and lncRNA signature are independent with other clinical risk factors in the multivariate Cox regression survival analyses. GSEAs revealed that autophagy-related biological processes are enriched in low-risk groups. Meng et al. Prognostic Autophagy Signature for Neuroblastoma Conclusions: Autophagy-related genes and lncRNAs are differentially expressed between stage 4 and stage 4s NB. The ARG signature and autophagy-related lncRNA signature successfully stratified NB patients into two risk groups. Autophagy-related biological processes are highly enriched in low-risk NB groups.

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Section: Discussionmentioning

confidence: 72%

Comparison of Stage 4 and Stage 4s Neuroblastoma Identifies Autophagy-Related Gene and LncRNA Signatures Associated With Prognosis

Meng

Fang

et al. 2020

Front. Oncol.

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“…When limonene was combined with berberine, synergistic anticancer effects were observed compared to either compound alone [170]. Light chain 3 (LC3) lipidation leading to autophagy was observed in neuroblastoma cells, and this lipidation was independent of ROS generation or ERK activation and caused a decrease in p62 levels [172,173]. Autophagy was also found in lung cancer cells lines and D-limonene suppressed tumor growth in murine models [174].…”

Section: Limonenementioning

confidence: 99%

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

Tomko

Whynot

Ellis

et al. 2020

Cancers

151

139

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In recent years, and even more since its legalization in several jurisdictions, cannabis and the endocannabinoid system have received an increasing amount of interest related to their potential exploitation in clinical settings. Cannabinoids have been suggested and shown to be effective in the treatment of various conditions. In cancer, the endocannabinoid system is altered in numerous types of tumours and can relate to cancer prognosis and disease outcome. Additionally, cannabinoids display anticancer effects in several models by suppressing the proliferation, migration and/or invasion of cancer cells, as well as tumour angiogenesis. However, the therapeutic use of cannabinoids is currently limited to the treatment of symptoms and pain associated with chemotherapy, while their potential use as cytotoxic drugs in chemotherapy still requires validation in patients. Along with cannabinoids, cannabis contains several other compounds that have also been shown to exert anti-tumorigenic actions. The potential anti-cancer effects of cannabinoids, terpenes and flavonoids, present in cannabis, are explored in this literature review.

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“…Murine raw 264.7 cell line TNF-α, IL-1, IL-6 [119] Human chondrocytes NF-kB, NO, iNOS, p38, JNK [70] Human lens epithelial cells ROS, CASP, MAPK, Bcl-2/Bax [120] Human neuroblastoma cells LC3, clonogenic capacity [121] Fruit fly NO [84] BALB/c mice NO [122] BALB/c mice Catalase, peroxidase [123] BALB/c mice IL-5, IL-13, MCP-1, TGF-β [124] BALB/c mice NF-kB, p38, JNK, ERK [125] Wistar rats NF-kB, COX-2, iNOS [126] Swiss mice IL-1β [127] Sprague-Dawley rats COX2, ERK, iNOS, MMP-2, MMP-9, PGE, TGF-β [128] BALB/c mice Apoptosis-related genes [129] Swiss…”

Section: Anti-inflammatory Antioxidantmentioning

confidence: 99%

Forest Volatile Organic Compounds and Their Effects on Human Health: A State-of-the-Art Review

Antonelli

Donelli

Barbieri³

et al. 2020

IJERPH

131

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The aim of this research work is to analyze the chemistry and diversity of forest VOCs (volatile organic compounds) and to outline their evidence-based effects on health. This research work was designed as a narrative overview of the scientific literature. Inhaling forest VOCs like limonene and pinene can result in useful antioxidant and anti-inflammatory effects on the airways, and the pharmacological activity of some terpenes absorbed through inhalation may be also beneficial to promote brain functions by decreasing mental fatigue, inducing relaxation, and improving cognitive performance and mood. The tree composition can markedly influence the concentration of specific VOCs in the forest air, which also exhibits cyclic diurnal variations. Moreover, beneficial psychological and physiological effects of visiting a forest cannot be solely attributed to VOC inhalation but are due to a global and integrated stimulation of the five senses, induced by all specific characteristics of the natural environment, with the visual component probably playing a fundamental role in the overall effect. Globally, these findings can have useful implications for individual wellbeing, public health, and landscape design. Further clinical and environmental studies are advised, since the majority of the existing evidence is derived from laboratory findings.

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Early LC3 lipidation induced by d -limonene does not rely on mTOR inhibition, ERK activation and ROS production and it is associated with reduced clonogenic capacity of SH-SY5Y neuroblastoma cells

Cited by 23 publications

References 23 publications

Comparison of Stage 4 and Stage 4s Neuroblastoma Identifies Autophagy-Related Gene and LncRNA Signatures Associated With Prognosis

Comparison of Stage 4 and Stage 4s Neuroblastoma Identifies Autophagy-Related Gene and LncRNA Signatures Associated With Prognosis

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

Forest Volatile Organic Compounds and Their Effects on Human Health: A State-of-the-Art Review

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