Biphosphinic palladacycle complex mediates lysosomal-membrane permeabilization and cell death in K562 leukaemia cells

Palladacycle (BPC) antitumour activity against resistant and metastatic cell lines: The relationship with cytosolic calcium mobilisation and cathepsin B activity

“…Once in the cytosol, these proteases participate in cell death by either apoptosis or necrosis [57,58]. In accordance with these findings, previous results reported by our group demonstrated the essential role of cathepsin B in BPC cytotoxicity to leukaemia cells [25,26]. These last authors described a reduction of caspase-3 and caspase-6 activity when a palladacycle complex BPC was pre-incubated with CA074, indicating that cathepsin B triggers leukaemia cells death and suggesting a direct relationship between cathepsin B and BPC activity.…”

“…Interestingly, parts of the BPC cytotoxic effects on leukaemia cells were dependent on LMP and cathepsin B activity. BPC has been shown to be a lysosomotropic agent, demonstrating an ability to lodge into acidic compartments, such as lysosomes [25]. Other important studies with palladium complexes were also reported.…”

“…One complex, called Biphosphinic Palladacycle Complex (BPC), was produced from the cyclisation of Pd by cyclometallation reactions [24]. This palladium complex is a chiral cyclopalladate derived from N,N-dimethyl-1-phenethylamine and the coordinating ligand 1,1 0 -bis(diphenylphosphine)ferrocene that exhibits lethal effects on human leukaemia cells and is ineffective against normal human lymphocytes [25,26]. Interestingly, parts of the BPC cytotoxic effects on leukaemia cells were dependent on LMP and cathepsin B activity.…”

Granulysin Induces Cathepsin B Release from Lysosomes of Target Tumor Cells to Attack Mitochondria through Processing of Bid Leading to Necroptosis

“…To further confirm the disruption of GNLY-induced lysosomal membrane, we detected its integrity by using a fluorogenic dye, AO. AO preferentially accumulates in acidic vesicles with a red fluorescence upon excitation with a blue light and it becomes a green fluorescence when it is presented in organelles of basic and neutral pH (29). After incubation with GNLY, lysosomal AO was released into the cytosol (Fig.…”

Encapsulation of <em>Piper cabralanum </em>(Piperaceae) nonpolar extract in poly(methyl methacrylate) by miniemulsion and evaluation of increase in the effectiveness of antileukemic activity in K562 cells

“…When the cell membrane loses its integrity, large molecules become permeable, indicating a possible sign of cell death. [40][41][42][43] To evaluate the cytotoxicity of polymeric NPs, the MTT assay was used, which evaluates mitochondrial integrity and is widely used to check the cell activity. Figure 7E and F shows the cytotoxic activity of polymeric NPs in K562 cells.…”