Chloroquine p53 lysosome

Discussion in 'Pharmacy Northwest Canada' started by seoserg, 08-Mar-2020.

  1. IL2 New Member

    Chloroquine p53 lysosome


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    Here we show that chloroquine, a drug that activates the stress-responsive Atm-p53 tumor-suppressor pathway, preferentially enhances the death of Myc oncogene-overexpressing primary mouse B cells and mouse embryonic fibroblasts MEFs and impairs Myc-induced lymphomagenesis in a transgenic mouse model of human Burkitt lymphoma. Chloroquine accumulates inside the acidic parts of the cell lysosomes and raises their pH, that way it inhibits autophagosome-lysosome fusion and degradation. This leads to accumulation of. While the proteasome inhibitors MG132 and bortezomib Velcade had no effect on the levels of mutant p53 protein, cathepsin inhibitor E64d and lysosomal inhibitors ammonium chloride NH 4 Cl and chloroquine ClQ further stabilized mutant p53 levels in ES-2 cells, suggesting that mutant p53 might be continuously degraded through the lysosomal pathway even under nonconfluent growth conditions Fig. 3A.

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    Chloroquine p53 lysosome

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    Chloroquine activates the p53 pathway and induces apoptosis in human glioma cells Chloroquine is a lysosomotropic agent that prevents endosomal acidification 1. It accumulates inside the acidic parts of the cell, including endosomes and lysosomes. This accumulation leads to inhibition of lysosomal enzymes that require an acidic pH, and prevents fusion of endosomes and lysosomes. In a mouse model of pancreatic tumours driven by Kras mutations, the outcome of suppressing autophagy is shown to depend on the status of p53 if p53 is intact, deletion of key autophagy genes.

     
  4. tikay XenForo Moderator

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  5. Hydroxychloroquine Side-effects, uses, time to work Hydroxychloroquine is commonly used alongside other disease-modifying drugs including methotrexate – especially for rheumatoid arthritis. However, some drugs can interact with hydroxychloroquine. Indigestion remedies for example, antacids including some over-the-counter preparations can stop hydroxychloroquine being absorbed.

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