IOX-101 reverses drug resistance through suppression of Akt/mTOR/NF κB signaling in cancer stem cell like, sphere forming NSCLC cells.

In this study we used drug resistant lung cancer stem like cells (A549-CS) to compare the efficacy of standard drugs like cisplatin (DDP) and gemcitabine (GEM) with a novel arylidene derivative IOX-101. A549-CS was derived from regular A549 cells by growing in special media. Resistance proteins were detected using Western Blotting. Cell proliferations were assessed by MTT assay. Cytokine release was enumerated using ELISA. Effect of drugs on apoptosis and cell cycle were studied with flow cytometry protocols. Apoptosis related proteins, caspases and other signaling protein expressions like Akt, mTOR were assessed by Western Blotting. Expression of CD 133 and NFκB phosphorylation was assessed using flow cytometry. A549-CS showed significant increase of CD 133 expression in comparison with A549 cells. Expression of resistance markers like MDR-1, LRP and GST-∏ were detected in A549-CS. While DDP, GEM had relatively lower efficacy in A549-CS, IOX-101 inhibited the proliferation of both A549 and A549-CS with GI50 values of 268 and 296.5 nM respectively. IOX-101 increased sub G0 phase in cell cycle of A549-CS and increased the percentage of apoptotic cells. Western Blot analysis revealed activation of caspases, Bax and reduction of Bcl-2 levels. Further mechanistic investigation revealed IOX101 to deactivate Akt, mTOR and NFκB signaling in A549-CS cells. Additionally, IOX-101 treatment to A549-CS also reversed MDR-1, LRP expressions. Collectively, our results demon...
Source: Oncology Research - Category: Cancer & Oncology Tags: Oncol Res Source Type: research

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ConclusionsWe predicted the regulatory factors involved in T cell exhaustion using single-cell transcriptome profiles of human TI lymphocytes. TOX promoted intra-tumoral CD8+ T cell exhaustion via upregulation of IC molecules. This suggested that TOX inhibition can potentially impede T cell exhaustion and improve ICI efficacy. Additionally,TOX expression in the TI T cells can be used for patient stratification during anti-tumor treatments, including anti-PD-1 immunotherapy.
Source: Genome Medicine - Category: Genetics & Stem Cells Source Type: research
Mesenchymal stem cells (MSCs) are pluripotent mesenchymal cells present in various adult tissues. MSCs secrete exosomes as regulators of the tumor niche, with involvement in tumorigenesis and metastasis. The r...
Source: Stem Cell Research and Therapy - Category: Stem Cells Authors: Tags: Research Source Type: research
Conclusion: These results showed that CD133 expression can be regulated by methylation. Thus, the demethylation of the CD133 promoter may compromise the treatment of lung cancer by inactivating cancer stem cells and/or activating CGAs. PMID: 32090054 [PubMed]
Source: Korean Journal of Thoracic and Cardiovascular Surgery - Category: Cardiovascular & Thoracic Surgery Tags: Korean J Thorac Cardiovasc Surg Source Type: research
Abstract Non-small-cell lung cancer (NSCLC) has become the most lethal human cancer because of the high rate of metastasis. Hence, clarifying the molecular mechanism underlying NSCLC metastasis is very important to improve the prognosis of patients with NSCLC. Long non-coding RNAs (LncRNAs) are a class of RNA molecules longer than 200 nucleotides, which can participate in diverse biological processes. About 18% of human LncRNAs were recently found to be associated with tumours. Many studies indicated that aberrant expression of LncRNAs played key roles in the progression and metastasis of NSCLC. According to the f...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
In conclusion, the concept of an epigenetic clock is compelling, but caution should be taken in interpreting associations with age acceleration. Association tests of age acceleration should include age as a covariate. A Discussion of Recent Work on Allotopic Expression of Mitochondrial Genes at the SENS Research Foundation https://www.fightaging.org/archives/2020/02/a-discussion-of-recent-work-on-allotopic-expression-of-mitochondrial-genes-at-the-sens-research-foundation/ A paper published last month outlines recent progress on allotopic expression of mitochondrial genes carried out by the SENS Research ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
We present a unique and successful case of a young patient with primary refractory ALK-positive LBCL who received salvage chemotherapy plus brigatinib followed by allogeneic stem cell transplantation.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 339 Source Type: research
In conclusion, chelerythrine chloride has the potential to mitigate cancer growth due to inhibitory actions toward the tumorigenic activity of CSC in lung cancer and it can be flexibly adjusted according to concentration to modulate specific targeting in different cell lines.
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
CONCLUSIONS These results suggest MCT-1/miR-34a/IL-6/IL-6R axis is responsible for MCT-1-mediated effects on NSCLC cell stemness. PMID: 31891569 [PubMed - in process]
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
Conclusions: Our results highlight the importance of a better characterization of cancer stem-like cells in ADENO and SQUAMO histotypes. This may suggest new differential approaches for prognostic and therapeutic purposes in patients with non-small-cell lung cancer.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study was in part funded by the National Institutes of Health.  
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
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