| Features: |
| Chloroquine (and its analogue hydroxychloroquine) Hydroxychloroquine (more commonly used because of its safety profile) Chloroquine originates from synthetic modifications of quinoline derivatives (it has roots in natural alkaloids like quinine) and is now produced through chemical synthesis. Its repurposing in cancer therapy centers on its ability to disrupt autophagy and lysosomal function, modulate the immune response within the tumor microenvironment, and sensitize cancer cells to chemo- and radiotherapy. Chloroquine is a synthetic derivative belonging to the 4-aminoquinoline class. It was initially developed in the 1930s from quinoline scaffolds, which themselves are derived from naturally occurring alkaloids like quinine (isolated from the bark of the cinchona tree). Unlike natural products that are directly extracted, chloroquine is produced by chemical synthesis in pharmaceutical laboratories. Pathways: -Autophagy Inhibition: By raising intralysosomal pH, chloroquine impairs the fusion of autophagosomes with lysosomes, thereby blocking autophagic flux. This inhibition can sensitize tumor cells to chemotherapy and enhance cell death. -Lysosomal Dysfunction: Chloroquine accumulates in lysosomes, altering their function. This can lead to lysosomal membrane permeabilization and subsequent activation of cell death pathways. -Stress-Related Signaling: Chloroquine-induced disruption of autophagy can lead to the accumulation of damaged proteins and organelles, triggering stress responses such as the unfolded protein response (UPR) and reactive oxygen species (ROS) generation. -TLR (Toll-Like Receptor) Signaling: There is evidence suggesting that chloroquine can inhibit TLR9 signaling Chemo- and Radiosensitization: -One of the promising uses of chloroquine in oncology is as an adjuvant to standard therapies. -By disrupting autophagy—a mechanism that many cancer cells use to survive after treatment—chloroquine can enhance the cytotoxic effects of chemotherapy and radiation. Hydroxychloroquine (more commonly used because of its safety profile) have used doses ranging from 400 mg per day up to 1200 mg per day in divided doses. Chloroquine effectiveness is pH sensitive: CQ concentrations in the whole-cell lysate were 7-fold lower at pH 6.8 as compared with pH 7.4 |
| Source: |
| Type: |
| Destruction of mitochondrial transmembrane potential, which is widely regarded as one of the earliest events in the process of cell apoptosis. Mitochondria are organelles within eukaryotic cells that produce adenosine triphosphate (ATP), the main energy molecule used by the cell. For this reason, the mitochondrion is sometimes referred to as “the powerhouse of the cell”. Mitochondria produce ATP through process of cellular respiration—specifically, aerobic respiration, which requires oxygen. The citric acid cycle, or Krebs cycle, takes place in the mitochondria. The mitochondrial membrane potential is widely used in assessing mitochondrial function as it relates to the mitochondrial capacity of ATP generation by oxidative phosphorylation. The mitochondrial membrane potential is a reliable indicator of mitochondrial health. In cancer cells, ΔΨm is often decreased, which can lead to changes in cellular metabolism, increased glycolysis, increased reactive oxygen species (ROS) production, and altered cell death pathways. The membrane of malignant mitochondria is hyperpolarized (−220 mV) in comparison to their healthy counterparts (−160 mV), which facilitates the penetration of positively charged molecules to the cancer cells mitochondria. The MMP is a critical indicator of mitochondrial function, directly reflecting the organelle's capacity to generate ATP through oxidative phosphorylation. |
| 1962- | GamB, | HCQ, | Gambogic acid induces autophagy and combines synergistically with chloroquine to suppress pancreatic cancer by increasing the accumulation of reactive oxygen species |
| - | in-vitro, | PC, | NA |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
Filter Conditions: Pro/AntiFlg:% IllCat:% CanType:% Cells:% prod#:271 Target#:197 State#:% Dir#:1
wNotes=0 sortOrder:rid,rpid