Autophagy in Cancer Chemoprevention: Identification of Novel Autophagy Modulators with Anticancer Potential

Cancer cells have the ability to tolerate extreme conditions, autophagy-related stress tolerance enables cancer cells to survive by maintaining energy production that leads to cell growth and therapeutic resistance. Insufficient activation of autophagy in nutrient-deprived cancer cells may sensitize cancer cells to a broad array of chemotherapeutic agents and ionizing radiation. Therefore, identification of novel autophagy modulators with lower toxicity and better therapeutic index would be beneficial for cancer therapy. Here, we describe several currently used biochemical methods to assess autophagic activity and lysosomal function in cultured cancer cells. We also discuss both in vitro and in vivo assays to clarify the anticancer potential of novel autophagy modulators.
Source: Springer protocols feed by Cancer Research - Category: Cancer & Oncology Source Type: news

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Cell cycle control genes are frequently mutated in cancer cells, which usually display higher rates of proliferation than normal cells. Dysregulated mitosis leads to genomic instability, which contributes to tumor progression and aggressiveness. Many drugs that disrupt mitosis have been studied because they induce cell cycle arrest and tumor cell death. These antitumor compounds are referred to as antimitotics. Vinca alkaloids and taxanes are natural products that target microtubules and inhibit mitosis, and their derivatives are among the most commonly used drugs in cancer therapy worldwide. However, severe adverse effect...
Source: Clinics - Category: General Medicine Source Type: research
Cancer is a leading cause of death worldwide, and its incidence is continually increasing. Although anticancer therapy has improved significantly, it still has limited efficacy for tumor eradication and is highly toxic to healthy cells. Thus, novel therapeutic strategies to improve chemotherapy, radiotherapy and targeted therapy are an important goal in cancer research. Macroautophagy (herein referred to as autophagy) is a conserved lysosomal degradation pathway for the intracellular recycling of macromolecules and clearance of damaged organelles and misfolded proteins to ensure cellular homeostasis. Dysfunctional autophag...
Source: Clinics - Category: General Medicine Source Type: research
We report that syrosingopine, an anti-hypertensive drug, is a dual MCT1 and MCT4 inhibitor (with 60-fold higher potency on MCT4) that prevents lactate and H+ efflux. Syrosingopine elicits synthetic lethality with metformin, an inhibitor of mitochondrial NADH dehydrogenase. NAD+, required for the ATP-generating steps of glycolysis, is regenerated from NADH by mitochondrial NADH dehydrogenase or lactate dehydrogenase. Syrosingopine treatment leads to high intracellular lactate levels and thereby end-product inhibition of lactate dehydrogenase. The loss of NAD+ regeneration capacity due to combined metformin and syrosingopine...
Source: Cell Reports - Category: Cytology Source Type: research
In this report, a highly efficient multifunctional anti-cancer nanocomposite was fabricated by assembling a photothermal agent (CuS nanoparticles) and a photodynamic agent (g-C3N4 quantum dots) on upconversion nanoparticles (UCNPs) after mesoporous silica coating. Then, the surface modification of the obtained nanocomposite (abbreviated as CUSCs) with polyethylene glycol (PEG) and folic acid (FA) endows the final sample (denoted as CUSCs-PEG-FA) with an excellent cancer cell targeting effect and biocompatibility. In this nanoplatform, CuS nanoparticles are an inorganic substance with low toxicity and high photothermal conv...
Source: Chemical Engineering Journal - Category: Chemistry Source Type: research
Phys. Chem. Chem. Phys., 2018, Accepted Manuscript DOI: 10.1039/C8CP06059B, PaperPatrick R Huddleston, Victor V Volkov, Carole Celia Perry Diversity of photo-switching structural elements open up new opportunities in the engineering of light driven reshaping of matter, in catalysis on-click including photodynamic cancer therapy, in light sensitive transport control... The content of this RSS Feed (c) The Royal Society of Chemistry
Source: RSC - Phys. Chem. Chem. Phys. latest articles - Category: Chemistry Authors: Source Type: research
MicroRNA‑363‑3p inhibits hepatocarcinogenesis by targeting HMGA2 and is associated with liver cancer stage. Mol Med Rep. 2018 Nov 29;: Authors: Wang J, Liang H, Ge H, Guo X, Gu D, Yuan Y Abstract The importance of microRNAs (miRNAs) in cancer development has been widely recognized in recent decades. In the present study, the function and mechanism of miRNA‑363‑3p (miR‑363‑3p), formerly characterized as a tumor suppressor, in the hepatocarcinogenesis of liver cancer cells was investigated. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was applied to detect the ex...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
ConclusionIn this review, the role of microbiota is explained in carcinogenesis, mechanisms of microbiota-mediated carcinogenesis, and role of gut microbiota in modulation of cancer therapy.
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
Existing drug discovery processes follow a reductionist model of“one-drug-one-gene-one-disease,” which is inadequate to tackle complex diseases involving multiple malfunctioned genes. The availability of big omics data offers opportunities to transform drug discovery process into a new paradigm of systems pharmacology that focuses on designing drugs to target molecular interaction networks instead of a single gene. Here, we develop a reliable multi-rank, multi-layered recommender system, ANTENNA, to mine large-scale chemical genomics and disease association data for prediction of novel drug-gene-disease associa...
Source: IEEE/ACM Transactions on Computational Biology and Bioinformatics - Category: Bioinformatics Source Type: research
Publication date: 10 December 2018Source: Cancer Cell, Volume 34, Issue 6Author(s): Delphine Merino, Gemma L. Kelly, Guillaume Lessene, Andrew H. Wei, Andrew W. Roberts, Andreas StrasserDefects in apoptotic cell death can promote cancer and impair responses of malignant cells to anti-cancer therapy. Pro-survival BCL-2 proteins prevent apoptosis by keeping the cell death effectors, BAX and BAK, in check. The BH3-only proteins initiate apoptosis by neutralizing the pro-survival BCL-2 proteins. Structural analysis and medicinal chemistry led to the development of small-molecule drugs that mimic the function of the BH3-only pr...
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research
Adoptive transfer of T cell receptor–engineered (TCR-engineered) T cells is a promising approach in cancer therapy but needs improvement for more effective treatment of solid tumors. While most clinical approaches have focused on CD8+ T cells, the importance of CD4+ T cells in mediating tumor regression has become apparent. Regarding shared (self) tumor antigens, it is unclear whether the human CD4+ T cell repertoire has been shaped by tolerance mechanisms and lacks highly functional TCRs suitable for therapy. Here, TCRs against the tumor-associated antigen NY-ESO-1 were isolated either from human CD4+ T cells or fro...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
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