Acid ceramidase inhibition sensitizes human colon cancer cells to oxaliplatin through downregulation of transglutaminase 2 and β1 integrin/FAK−mediated signalling

Klobučar, Marko; Grbčić, Petra; Pavelić, Sandra Kraljević; Jonjić, Nives; Visentin, Sarah; Sedić, Mirela

doi:10.1016/j.bbrc.2018.06.085

Cited by 22 publications

(19 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, high expression of ASAH1 was associated with improved prognosis in invasive breast cancer [34]. High expression of ASAH1 was also found in human colon cancer cells and colorectal adenocarcinoma tissues and was shown to be negatively correlated with p53 functional activity in tumor cells [35]. Furthermore, low ASAH1 expression was associated with invasive behavior of melanoma cells and therefore, may present a new therapeutic target [37].…”

Section: Plos Onementioning

confidence: 99%

“…In turn, a substrate of sphingosine kinases catalyzes the conversion of sphingosine into mitogenic sphingosine-1-phosphate [33]. The ASAH1 enzyme is overexpressed in multiple human cancers and may promote cancer progression [33][34][35][36]. Stable knockdown of ASAH1 in a prostate cancer cell line (PC-3/Mc) caused accumulation of ceramides, an increased requirement for growth factors, and inhibition of tumor cell proliferation and migration [33].…”

Section: Plos Onementioning

confidence: 99%

See 1 more Smart Citation

Transcriptome analysis reveals gender-specific differences in overall metabolic response of male and female patients in lung adenocarcinoma

et al. 2020

PLoS ONE

View full text Add to dashboard Cite

Background Evidence from multiple studies suggests metabolic abnormalities play an important role in lung cancer. Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. The present study aimed to explore differences in the global metabolic response between male and female patients in LUAD and to identify the metabolic genes associated with lung cancer susceptibility. Methods Transcriptome and clinical LUAD data were acquired from The Cancer Genome Atlas (TCGA) database. Information on metabolic genes and metabolic subsystems were collected from the Recon3D human metabolic model. Two validation datasets (GSE68465 and GSE72094) were downloaded from the Gene Expression Omnibus (GEO) database. Differential expression analysis, gene set enrichment analysis and protein-protein interaction networks were used to identified key metabolic pathways and genes. Functional experiments were used to verify the effects of genes on proliferation, migration, and invasion in lung cancer cells in vitro. Results Samples of tumors and adjacent non-tumor tissue from both male and female patients exhibited distinct global patterns of gene expression. In addition, we found large differences in methionine and cysteine metabolism, pyruvate metabolism, cholesterol metabolism, nicotinamide adenine dinucleotide (NAD) metabolism, and nuclear transport between male and female LUAD patients. We identified 34 metabolic genes associated with lung cancer

show abstract

Section: Plos Onementioning

confidence: 99%

Section: Plos Onementioning

confidence: 99%

Transcriptome analysis reveals gender-specific differences in overall metabolic response of male and female patients in lung adenocarcinoma

et al. 2020

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…ASAH1 has been identified in cancer cells and is associated with radiotherapy/chemotherapy-resistant tumors [ 22 , 55 , 56 , 57 ], metastatic cell lines [ 58 ], and estrogen/progesterone/androgen receptor-positive cells [ 59 , 60 ]. While ACDase gene overexpression has been identified in low-survival-rate colorectal adenocarcinoma and glioblastoma [ 57 , 61 ], it has also been observed in node-negative melanoma and breast cancer [ 59 , 62 ], which makes it a questionable marker for the aggressiveness or invasiveness of the disease.…”

Section: Role Of Ceramidase Activity In Human Non-heritable Diseasmentioning

confidence: 99%

“…ACDase deletion blocks the cell cycle at G1/S, promotes senescence through the β-Galactosidase/MITF pathway, induces apoptosis, reduces tumorigenesis, increases growth arrest, and decreases malignancy [ 68 ]. It was demonstrated that the activity of ACDase was significantly inhibited by Carmofur [ 55 , 58 ], LCL521 [ 19 , 65 , 69 , 70 ], Ceranib2 [ 24 , 71 , 72 , 73 ], N-oleocylethanolamine (NOE) [ 22 , 57 ], ARN14988 [ 74 ], LCL204 [ 10 , 64 ], Monascus Purperus (MP) [ 18 ], Hesperetin (Hst) [ 17 ], Hesperetine-7-O-acetate (HTA) [ 17 ], Silibinin [ 20 ], Curcumin [ 23 ], and Sanguinarine [ 21 , 75 ], leading to an increased accumulation of intracellular ceramide and apoptosis in various types of cancer cells, including glioblastoma; squamous cell carcinoma; acute myeloid leukemia; colorectal adenocarcinoma; and breast, prostate, lung, gastric, and kidney cancer. Furthermore, Carmofur, NOE, LCL521, and Ceranib2 have been used in combination with chemotherapeutic drugs or photodynamic therapy to either overcome cancer cell resistance to treatment, increase cell sensitivity to specific drugs, or increase the overall effectiveness of cancer cell apoptosis [ 22 , 55 , 58 , 70 , 72 , 73 ].…”

Section: Role Of Ceramidase Activity In Human Non-heritable Diseasmentioning

confidence: 99%

Elusive Roles of the Different Ceramidases in Human Health, Pathophysiology, and Tissue Regeneration

Duarte

Akkaoui

Yamada

et al. 2020

Cells

View full text Add to dashboard Cite

Ceramide and sphingosine are important interconvertible sphingolipid metabolites which govern various signaling pathways related to different aspects of cell survival and senescence. The conversion of ceramide into sphingosine is mediated by ceramidases. Altogether, five human ceramidases—named acid ceramidase, neutral ceramidase, alkaline ceramidase 1, alkaline ceramidase 2, and alkaline ceramidase 3—have been identified as having maximal activities in acidic, neutral, and alkaline environments, respectively. All five ceramidases have received increased attention for their implications in various diseases, including cancer, Alzheimer’s disease, and Farber disease. Furthermore, the potential anti-inflammatory and anti-apoptotic effects of ceramidases in host cells exposed to pathogenic bacteria and viruses have also been demonstrated. While ceramidases have been a subject of study in recent decades, our knowledge of their pathophysiology remains limited. Thus, this review provides a critical evaluation and interpretive analysis of existing literature on the role of acid, neutral, and alkaline ceramidases in relation to human health and various diseases, including cancer, neurodegenerative diseases, and infectious diseases. In addition, the essential impact of ceramidases on tissue regeneration, as well as their usefulness in enzyme replacement therapy, is also discussed.

show abstract

“…GE exerted cytotoxic and antitumor activities on various types of cancers (▶ Table 1). Colon cancer ranks as the fourth leading cause of cancer mortality worldwide [9]. A recent study demonstrated that GE could significantly inhibit cell growth in the colon cancer cell line colo-205 with an IC 50 value of 20 µM.…”

Section: Cytotoxic and Antitumor Activitiesmentioning

confidence: 99%

Pharmacological Properties of Geraniol – A Review

et al. 2018

View full text Add to dashboard Cite

Geraniol is an acyclic isoprenoid monoterpene isolated from the essential oils of aromatic plants including Cinnamomum tenuipilum, Valeriana officinalis, and several other plants. The limited source of geraniol from plant isolation cannot fulfill the great demand from the flavor and fragrance industries, which require maximizing geraniol production through biotechnology processes. The diverse activities of geraniol suggested that geraniol could treat various diseases as a promising drug candidate. In order to evaluate the potential of geraniol applied in a clinical trial, this review aims at providing a comprehensive summary of the pharmacological effects of geraniol. The publications retrieved from PubMed, ScienceDirect, Springer, and Wiley databases were collected and summarized for the last 6 years. Then, the potential application of geraniol as a drug is discussed based on its pharmacological properties, including antitumor, anti-inflammatory, antioxidative, and antimicrobial activities, and hepatoprotective, cardioprotective, and neuroprotective effects. Hence, this review aims at providing evidence of the pharmacological activities of geraniol in the context of further development as a drug candidate in clinical application.

show abstract

Acid ceramidase inhibition sensitizes human colon cancer cells to oxaliplatin through downregulation of transglutaminase 2 and β1 integrin/FAK−mediated signalling

Cited by 22 publications

References 28 publications

Transcriptome analysis reveals gender-specific differences in overall metabolic response of male and female patients in lung adenocarcinoma

Transcriptome analysis reveals gender-specific differences in overall metabolic response of male and female patients in lung adenocarcinoma

Elusive Roles of the Different Ceramidases in Human Health, Pathophysiology, and Tissue Regeneration

Pharmacological Properties of Geraniol – A Review

Contact Info

Product

Resources

About