Dataset Information

Fenugreek extract as an inducer of cellular death via autophagy in human T lymphoma Jurkat cells.

ABSTRACT:

Background

Drugs used both in classical chemotherapy and the more recent targeted therapy do not have cancer cell specificity and, hence, cause severe systemic side effects. Tumors also develop resistance to such drugs due to heterogeneity of cell types and clonal selection. Several traditional dietary ingredients from plants, on the other hand, have been shown to act on multiple targets/pathways, and may overcome drug resistance. The dietary agents are safe and readily available. However, application of plant components for cancer treatment/prevention requires better understanding of anticancer functions and elucidation of their mechanisms of action. The current study focuses on the anticancer properties of fenugreek, a herb with proven anti-diabetic, antitumor and immune-stimulating functions.

Method

Jurkat cells were incubated with 30 to 1500 ?g/mL concentrations of 50% ethanolic extract of dry fenugreek seeds and were followed for changes in viability (trypan blue assay), morphology (microscopic examination) and autophagic marker LC3 transcript level (RT-PCR).

Results

Incubation of Jurkat cells with fenugreek extract at concentrations ranging from 30 to 1500 ?g/mL for up to 3 days resulted in cell death in a dose- and time-dependent manner. Jurkat cell death was preceded by the appearance of multiple large vacuoles, which coincided with transcriptional up-regulation of LC3. GC-MS analysis of fenugreek extract indicated the presence of several compounds with anticancer properties, including gingerol (4.82%), cedrene (2.91%), zingerone (16.5%), vanillin (1.52%) and eugenol (1.25%).

Conclusions

Distinct morphological changes involving appearance of large vacuoles, membrane disintegration and increased expression of LC3 transcripts indicated that fenugreek extract induced autophagy and autophagy-associated death of Jurkat cells. In addition to the already known apoptotic activation, induction of autophagy may be an additional mechanism underlying the anticancer properties of fenugreek. This is the first report showing fenugreek as an inducer of autophagy in human cells and further work is needed to define the various intermediates of the autophagic pathway.

SUBMITTER: Al-Daghri NM

PROVIDER: S-EPMC3520713 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Fenugreek extract as an inducer of cellular death via autophagy in human T lymphoma Jurkat cells.

Al-Daghri Nasser M NM Alokail Majed S MS Alkharfy Khalid M KM Mohammed Abdul Khader AK Abd-Alrahman Sherif H SH Yakout Sobhy M SM Amer Osama E OE Krishnaswamy Soundararajan S

BMC complementary and alternative medicine 20121030

<h4>Background</h4>Drugs used both in classical chemotherapy and the more recent targeted therapy do not have cancer cell specificity and, hence, cause severe systemic side effects. Tumors also develop resistance to such drugs due to heterogeneity of cell types and clonal selection. Several traditional dietary ingredients from plants, on the other hand, have been shown to act on multiple targets/pathways, and may overcome drug resistance. The dietary agents are safe and readily available. Howeve ...[more]

PMID: 23110539

Similar Datasets

Project description:Trehalose is a natural dietary molecule that has shown antiaging and neuroprotective effects in several animal models of neurodegenerative diseases. The role of trehalose in the management of age-related macular degeneration (AMD) is yet to be investigated and whether trehalose could be a remedy for the treatment of diseases linked to oxidative stress and NRF2 dysregulation. Here, we showed that incubation of human retinal pigment epithelial (RPE) cells with trehalose enhanced the mRNA and protein expressions of TFEB, autophagy genes ATG5 and ATG7, as well as protein expressions of macroautophagy markers, LC3B and p62/SQTM1, and the chaperone-mediated autophagy (CMA) receptor LAMP2. Cathepsin D, a hydrolytic lysosomal enzyme, was also increased by trehalose, indicating higher proteolytic activity. Moreover, trehalose upregulated autophagy flux evident by an increase in the endogenous LC3B level, and accumulation of GFP-LC3B puncta and free GFP fragments in GFP-LC3 - expressing cells in the presence of chloroquine. In addition, the mRNA levels of key molecular targets implicated in RPE damage and AMD, such as vascular endothelial growth factor- (VEGF-) A and heat shock protein 27 (HSP27), were downregulated, whereas NRF2 was upregulated by trehalose. Subsequently, we mimicked in vitro AMD conditions using hydroquinone (HQ) as the oxidative insult on RPE cells and evaluated the cytoprotective effect of trehalose compared to vehicle treatment. HQ depleted NRF2, increased oxidative stress, and reduced the viability of cells, while trehalose pretreatment protected against HQ-induced toxicity. The cytoprotection by trehalose was dependent on autophagy but not NRF2 activation, since autophagy inhibition by shRNA knockdown of ATG5 led to a loss of the protective effect. The results support the transcriptional upregulation of TFEB and autophagy by trehalose and its protection against HQ-induced oxidative damage in RPE cells. Further investigation is, therefore, warranted into the therapeutic value of trehalose in alleviating AMD and retinal diseases associated with impaired NRF2 antioxidant defense.

Project description:BackgroundGlioblastoma multiforme (GBM) is the most malignant adult brain tumor. Current standard of care treatments have very limited efficacy, being the patients´ overall survival 14 months and the 2-year survival rate less than 10%. Therefore, the treatment of GBM is an urgent unmet clinical need.MethodsThe aim of this study was to investigate in vitro and in vivo the potential of ABTL0812, an oral anticancer compound currently in phase II clinical stage, as a novel therapy for GBM.ResultsWe showed that ABTL0812 inhibits cell proliferation in a wide panel of GBM cell lines and patient-derived glioblastoma stem cells (GSCs) with half maximal inhibitory concentrations (IC50s) ranging from 15.2 µM to 46.9 µM. Additionally, ABTL0812 decreased GSCs neurosphere formation. GBM cells aggressiveness is associated with a trans-differentiation process towards a less differentiated phenotype known as proneural to mesenchymal transition (PMT). ABTL0812 was shown to revert PMT and induce cell differentiation to a less malignant phenotype in GBM cell lines and GSCs, and consequently reduced cell invasion. As previously shown in other cancer types, we demonstrated that the molecular mechanism of action of ABTL0812 in glioblastoma involves the inhibition of Akt/mTORC1 axis by overexpression of TRIB3, and the activation of endoplasmic reticulum (ER) stress/unfolded protein response (UPR). Both actions converge to induce autophagy-mediated cell death. ABTL0812 anticancer efficacy was studied in vivo using subcutaneous and orthotopic intra-brain xenograft tumor models. We demonstrated that ABTL0812 impairs tumor growth and increases disease-free survival and overall survival of mice. Furthermore, the histological analysis of tumors indicated that ABTL0812 decreases angiogenesis. Finally, we investigated the combination of ABTL0812 with the standard of care treatments for GBM radiotherapy and temozolomide in an orthotopic model, detecting that ABTL0812 potentiates the efficacy of both treatments and that the strongest effect is obtained with the triple combination of ABTL0812+radiotherapy+temozolomide.ConclusionsOverall, the present study demonstrated the anticancer efficacy of ABTL0812 as single agent and in combination with the GBM standard of care treatments in models of glioblastoma and supports the clinical investigation of ABTL0812 as a potential novel therapy for this aggressive brain tumor type.

Dataset Information

Fenugreek extract as an inducer of cellular death via autophagy in human T lymphoma Jurkat cells.

Background

Method

Results

Conclusions

Publications

Fenugreek extract as an inducer of cellular death via autophagy in human T lymphoma Jurkat cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets