Chloroquine diphosphate is used as an antimalarial drug and also functions to increase sensitivity of tumor cells to radiation and chemotherapy via inducing autophagy . Chloroquine diphosphate has been reported as an adjuvant for radiation and chemotherapy for inducing cell autophagy to anti-Y cells proliferation or metastasis . The mechanism of chloroquine diphosphate inducing cells autophagy is arresting cells in G1, up-regulates the expression of p27 and p53 while down-regulates the expression of CDK2 and cyclin D1 . Apart from anti-malarial, chloroquine diphosphate also has long been reported functioning in cell apoptosis. Pretreated CNE-2 human nasopharyngeal carcinoma cells with chloroquine diphosphate enhanced ionizing radiation induced cell apoptosis via increasing cells autophagic ratio . When treated with mouse breast Y 4T1 cells, chloroquine diphosphate treatment inhibited cellular proliferation and viability which resulted in cells apoptosis in a time- and dose- dependent manner . In human colon Y DLD-1 cells, combination of 5-FU and chloroquine diphosphate could inhibit cells proliferation via inducing autophagy.(In Vitro):Chloroquine (CHQ, 20 μM) inhibits IL-12p70 release and reduces Th1-priming capacity of activated human monocyte-derived Langerhans-like cells (MoLC). Chloroquine (CHQ, 20 μM) enhances IL-1–induced IL-23 secretion in MoLC and subsequently increases IL-17A release by primed CD4+ T cells. Chloroquine (25 μM) suppresses MMP-9 mRNA expression in normoxia and hypoxia in parental MDA-MB-231 cells. Chloroquine has cell-, dose- and hypoxia-dependent effects on MMP-2, MMP-9 and MMP-13 mRNA expression. TLR7 and TLR9 inhibition using IRS-954 or chloroquine significantly reduces HuH7 cell proliferation in vitro.Chloroquine (0.01-100 μM; 48 hours) potently blocks virus infection (vero E6 cells infected with SARS-CoV-2) at low-micromolar concentration (EC50= 1.13 μM). Chloroquine blocks virus infection by increasing endosomal pH required for virus/cell fusion, as well as interfering with the glycosylation of cellular receptors of SARS-CoV.(In Vivo):Chloroquine (80 mg/kg, i.p.) does not prevent the growth of the triple-negative MDA-MB-231 cells with high or low TLR9 expression levels in the orthotopic mouse model. TLR7 and TLR9 inhibition using IRS-954 or chloroquine significantly inhibits tumour growth in the mouse xenograft model. HCC development in the DEN/NMOR rat model is also significantly inhibited by chloroquine.
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