Chloroquine autophagy inhibition

Discussion in 'Canadian Drugs' started by vborg, 21-Feb-2020.

  1. eksstroy Guest

    Chloroquine autophagy inhibition


    Chloroquine has been extensively used in mass drug administrations, which may have contributed to the emergence and spread of resistance. It is recommended to check if chloroquine is still effective in the region prior to using it.

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    Autophagy inhibition is a potential therapeutic strategy in cancer, but it is unknown which tumors will benefit. The BRAFV600E mutation has been identified as important in pediatric central nervous system CNS tumors and is known to affect autophagy in other tumor types. We evaluated CNS tumor cells with BRAFV600E and found that mutant but not wild-type cells display high rates of induced. Activation of p53 was associated with the rapid appearance of apoptotic cells and the induction of autophagy in surviving cells. Inhibition of autophagy with either chloroquine or ATG5 short hairpin RNA shRNA enhanced the ability of either p53 activation or alkylating drug therapy to induce tumor cell death. These studies provide evidence. Several lysosomal inhibitors such as bafilomycin A1 BafA1, protease inhibitors and chloroquine CQ, have been used interchangeably to block autophagy in in vitro experiments assuming that they all primarily block lysosomal degradation.

    The Centers for Disease Control and Prevention recommend against treatment of malaria with chloroquine alone due to more effective combinations. In areas where resistance is present, other antimalarials, such as mefloquine or atovaquone, may be used instead.

    Chloroquine autophagy inhibition

    Inhibition of autophagy with chloroquine enhances therapeutic., JCI - Autophagy inhibition enhances therapy-induced apoptosis.

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  4. Furthermore, mtDNA levels were unchanged but damage was increased. These findings are consistent with a secondary effect on bioenergetics by bafilomycin and chloroquine due to autophagy inhibition and a resulting decrease in mitochondrial quality.

    • Inhibition of autophagy with bafilomycin and chloroquine decreases..
    • Chloroquine inhibits autophagic flux by decreasing autophagosome..
    • Autophagy Inhibitor Chloroquine Enhanced the Cell Death..

    Autophagy is a homeostatic cellular recycling system that is responsible for degrading damaged or unnecessary cellular organelles and proteins. Cancer cells are thought to use autophagy as a source of energy in the unfavorable metastatic environment, and a number of clinical trials are now revealing the promising role of chloroquine, an autophagy inhibitor, as a novel antitumor drug. On the. Autophagy has a pro-tumorigenic role in established tumors and consequently the vast majority of clinical trials focus on autophagy inhibition in cancer. Over the last decade, a dozen Phase I and I/II clinical trials have been completed and published using the autophagy inhibitors, Chloroquine CQ or hydroxychloroquine HCQ in cancer. These. Chloroquine is commonly used to study the role of endosomal acidification in cellular processes 2, 3, such as the signaling of intracellular TLRs. Moreover, Chloroquine inhibits autophagy as it raises the lysosomal pH, which leads to inhibition of both fusion of autophagosome with lysosome and lysosomal protein degradation 4. References. 1.

     
  5. Freeline Guest

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  6. ply1 Moderator

    Plaquenil hydroxychloroquine sulfate dose, indications. Mg 620 mg base PO as a single dose for malaria with a total of 2 g 1.55 g base PO in 48 hours; 400 mg/week 310 mg base/week PO for malaria prophylaxis; 600 mg/day 465 mg base/day PO for other indications.

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  7. forfun Well-Known Member

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