chloroquine phosphate

Chloroquine is a widely used anti-malarial drug that triggers lysosome membrane permeabilization (LMP) to liberate sequestered drugs from these organelles...This can be achieved on fixed cells by detecting endogenous LGALS3 with immunostaining or by the visualization of a transgenic LGALS3-mCherry fusion protein on live cells. Altogether, these methods facilitate qualitative and quantitative fluorescence imaging of lysosomal sequestration and liberation of lysosomotropic drugs.

Autophagy was shown to induce cell death since its inhibition using chloroquine (CQ) significantly decreased [HuArgI (Co)-PEG5000]-induced cytotoxicity, indicating autophagic cell death in AML cells following arginine deprivation. Moreover, we showed that arginine deprivation leads to ROS accumulation and that neutralizing ROS using N-acetylcysteine (NAC) does not affect the autophagic response but completely reverses the cytotoxicity of arginine deprivation, demonstrating that death by autophagy is dependent on ROS generation in AML cells.

In FLT3-ITD AML cell lines (MOLM13 and MV4-11), treatment with first- and second-generation FLT3i (midostaurin and quizartinib, respectively) induced autophagy. The combination of quizartinib and chloroquine demonstrated a synergistic effect in MV4-11QR cells and this effect was associated with greater inhibition of the FLT3 receptor compared to the monotherapies. Therefore, combining FLT3i with autophagy inhibition enhances the FLT3i antileukemic efficacy and overcomes pharmacological resistance.

Hydrophobic weakly basic drugs, such as doxorubicin and sunitinib, are currently key components of cancer chemotherapy...Co-treatment with doxorubicin and chloroquine, a well-established lysosomotropic agent, results in the increased lysosomal volume under both normoxic and hypoxic conditions...A similar effect, lysosomal volume expansion and enhanced degradative capacity in response to doxorubicin, was also observed in the human fibrosarcoma cell line HT1080. In summary, this study provides the first evidence that doxorubicin directly modulates lysosomal parameters in the tumor cell lines under varying oxygen concentrations.

Cells were pretreated with chloroquine before OAC treatment...OAC effectively inhibits cell proliferation and induces apoptosis and autophagy in A549 cells, with PTEN playing a regulatory role in these processes. These findings suggest that OAC may serve as a potential therapeutic agent for cancer treatment.

Leveraging this property, neuroblastoma-derived exosomes can be purified, modified, and loaded with small interfering RNA (siRNA) to silence MYCN expression, combined with chloroquine-an FDA-approved autophagy inhibitor-to simultaneously inhibit autophagy and induce apoptotic signaling...Collectively, exosome-based strategies represent a paradigm shift in formulating combination therapies, offering a multifaceted approach to target MYCN amplification, inhibit autophagy, induce apoptosis, and modulate the tumor-microbiome axis. These innovations hold significant promise for improving clinical outcomes in high-risk MYCN-amplified neuroblastoma patients.

In sum, the results of this study indicate that CQP effectively inhibits ASFV replication by suppressing the MAPK-ERK signaling pathway. This study provides a theoretical basis and technical support for the development of anti-viral strategies targeting ASFV.

Atractylon treatment for 12 h activated autophagic flux, because atractylon-induced autophagy was abolished by 3-methyladenine but was enhanced by chloroquine or bafilomycin A1. Furthermore, loss of MMP and activation of caspases upon atractylon treatment were abrogated by 3-methyladenine or autophagy-related gene 3 (ATG3) siRNA in HepG2 cells, suggesting that autophagy activation was required for induction of apoptosis. Altogether, atractylon disrupted the PI3K/AKT/mTOR signaling leading to autophagy-dependent apoptosis, which could be a promising candidate for anti-hepatoma therapy.

Cycloheximide chase assays, PS-341, and chloroquine treatment were used to explore the mechanisms of PD-1 downregulatory effects by apigenin...In vivo experiments confirmed that combined treatment noticeably inhibited melanoma growth and enhanced T cell infiltration into melanoma tissues. Apigenin promoted the degradation of PD-1 in T cells via the proteasomal pathway, in addition to synergizing with chemo/radiotherapy to inhibit melanoma growth.

Here, we report that combining the BET inhibitor JQ1 with the autophagy inhibitor chloroquine (CQ) synergistically amplifies ERS, leading to enhanced ICD in OSCC models. This minimally invasive platform ensures sustained drug release, improves tumor accumulation, and minimizes systemic exposure. Our study not only elucidates a druggable autophagy-ERS-ICD axis but also provides a versatile transdermal delivery strategy with potential applicability to a range of solid tumors.

Notably, co-treatment with chloroquine, an autophagy inhibitor, partially rescued cell viability, underscoring that autophagy contributes to PBE-induced cell death. In addition, PBE modulated several critical signaling pathways by inhibiting EGFR, mTOR, and STAT3 while concurrently activating downstream ERK and the AMPK-ACC axis. Collectively, these results reveal that PBE triggers ER stress-mediated UPR and autophagy to promote autophagic cell death in CRC, supporting its potential development as a novel therapeutic agent for colorectal cancer.

Notably, chloroquine (CQ), an autophagy inhibitor, enhances HPSCC sensitivity to 5-fluorouracil (5-FU), with synergistic effects observed in xenograft models. These findings establish the Trim15-VDAC3-mitophagy axis as a critical regulator of HPSCC progression and chemoresistance, offering a novel therapeutic target for augmenting the efficacy of autophagy inhibitors in combination with standard chemotherapy.