PAO-PDT

PAO-PDT is an organoarsenic inhibitor of thioredoxin reductase (TrxR), with an IC₅₀ of 33 nM. PAO-PDT can bind to the C-terminal selenocysteine/cysteine pair of TrxR and convert the enzyme into an NADPH oxidase, which increases reactive oxygen species levels and impairs mitochondrial respiratory function, thereby inducing apoptosis in leukemia cells. PAO-PDT can be used for leukemia research^[1][2][3][4]. In Vitro:PAO-PDT (compound 4) selectively and potently inhibits the proliferation of human promyelocytic leukemia HL-60 cells within 48-72 h, with IC₅₀ values of 0.7 μM (48 h) and 0.6 μM (72 h), respectively, while exhibiting low cytotoxicity against other cancer cell lines and normal cells^[1].
PAO-PDT (2.0-5.0 μM; 48 h) exhibits weak effects on human embryonic kidney HEK-TrxR1 cells with overexpressed TrxR, whereas human cervical carcinoma HeLa-shTrxR1 cells with TrxR knockdown are more sensitive to PAO-PDT, which confirms that TrxR targeting mediates the cytotoxicity of PAO-PDT^[1].
PAO-PDT (48 h) inhibits the proliferation of HL-60 cells, with an IC₅₀ of 0.70 μM after 48 h of incubation^[2].
PAO-PDT (compound 8) (48 h) potently inhibits the viability of HL-60 leukemia cells with an IC₅₀ of 0.81 μM, and exhibits low cytotoxicity against HeLa, SMMC-7721, and HepG2 cells^[4].
PAO-PDT (24-48 h) inhibits the viability of NB4, HL-60, HeLa, SGC7901, MCF-7, and HEK293 cells in vitro, with the highest potency against NB4 cells (IC₅₀ = 0.82 μM at 48 h)^[3].
PAO-PDT (0.6-3.6 μM; 1-8 h) induces a time- and concentration-dependent decrease in the viability of NB4 cells in vitro, and after incubation with 3.6 μM PAO-PDT for 8 h, the cell viability decreases to approximately 0.38^[3].
PAO-PDT (50-200 nM) potently inhibits the purified wild-type TrxR at concentrations of 50 nM and above, but does not inhibit the purified U498C mutant TrxR at the same concentrations^[1].
PAO-PDT inhibits recombinant rat wild-type thioredoxin reductase with an IC₅₀ of approximately 33 nM, and exhibits no significant inhibitory effect on U498C TrxR, GR, GPx, or Trx^[1].
PAO-PDT (1-2 μM; 12-24 h) inhibits the activity of cellular thioredoxin reductase in human promyelocytic leukemia HL-60 cells, with an IC₅₀ of approximately 1.4 μM; it also directly binds to endogenous TrxR1 and upregulates the expression of TrxR1 protein at concentrations of 1 μM (24 h) and 2 μM (12 h)^[1].
PAO-PDT (1-10 μM; 12-24 h) induces concentration-dependent cellular thiol depletion in human promyelocytic leukemia HL-60 cells, and the degree of depletion after 24 h is greater than that after 12 h^[1].
PAO-PDT potently inhibits purified TrxR with an IC₅₀ of 33 nM^[2].
PAO-PDT (30 min) inhibits the activity of purified recombinant rat TrxR1 and exhibits extremely low inhibitory activity against GR^[4].
PAO-PDT (2 μM; 24 h) inhibits cellular TrxR activity in HL-60 cells by approximately 40%^[4].
PAO-PDT (1 μM; 1-2 h) induces time-dependent reactive oxygen species accumulation in human promyelocytic leukemia HL-60 cells^[1].
PAO-PDT (1.2 μM; 1-6 h) induces mild short-term ROS accumulation in NB4 cells in vitro^[3].
PDT-PAO (15-100 μM) regulates mitochondrial respiration in isolated rat liver mitochondria^[3].
PDT-PAO (0.3-2.4 μM; 24 h) increases the intracellular ROS level in NB4 cells in a concentration-dependent manner in vitro, and the induction effect reaches its peak at 2.4 μM^[3].
The cytotoxicity of PAO-PDT (0.01-2.0 μM; 48 h) against human promyelocytic leukemia HL-60 cells is inhibited by Acetylcysteine (HY-B0215) in a dose-dependent manner, while pretreatment with L-Buthionine-(S,R)-sulfoximine (HY-106376A) enhances the cytotoxicity of PAO-PDT^[1].
PAO-PDT (0.5-5 μM; 12-24 h) induces dose- and time-dependent apoptotic cell death in human promyelocytic leukemia HL-60 cells, and the proportion of apoptotic cells observed at 24 h is higher than that at 12 h^[1].
PAO-PDT (0.5-2 μM; 24 h) induces concentration-dependent activation of caspase-3 in human promyelocytic leukemia HL-60 cells after 24 h of treatment^[1].
PAO-PDT (0.5-5 μM; 24 h) induces apoptotic nuclear morphology in human promyelocytic leukemia HL-60 cells after 24 h of treatment, characterized by nuclear pyknosis and high fluorescence intensity^[1].
PDT-PAO (0.6-2.4 μM; 4-24 h) reduces the total thiol level in NB4 cells in a concentration- and time-dependent manner, with the most potent reduction observed after treatment with 2.4 μM for 24 h^[3].
PDT-PAO (1.2-2.4 μM; 24 h) increases the level of cytochrome c in NB4 cells^[3].
PAO-PDT (1.2 μM; 1-6 h) induces a slight time-dependent collapse of mitochondrial membrane potential in NB4 cells in vitro^[3].
PAO-PDT (1.2-2.4 μM; 24 h) reduces the intracellular ATP level in NB4 cells in a concentration-dependent manner in vitro. After incubation with 2.4 μM PAO-PDT for 24 h, the ATP level decreases to ~5 μmol/g protein^[3].
PAO-PDT (50-200 μM) inhibits thermogenesis in isolated mitochondria from NB4 cells in vitro. At 100 μM, it reduces the maximum power output to 96.9 μW and slows the rate constants of the activity recovery phase, steady-state rise phase, and decline phase^[3].
PDT-PAO (1-5 μM; 2.5-5 h) inhibits PDHC activity in NB4 cells, and the enzyme activity in the treatment groups at concentrations of 1 μM and 5 μM (incubated for 2.5 h) as well as 2.4 μM (incubated for 5 h) decreases compared with the untreated control group^[3].
PDT-PAO (2.4 μM; 24 h) reduces the viability of NB4 cells, and this effect is reversed in a concentration-dependent manner upon combined treatment with LA^[3].
PDT-PAO (1.5-2 μM; 24 h) reduces the viability of NB4 cells, and this effect is observed at both concentrations of 1.5 μM and 2 μM (with 24 h incubation); however, this effect is reversed in a concentration-dependent manner upon combined treatment with DL-Dithiothreitol (DTT) (HY-15917), Dimethyl phthalate (DMP) (HY-N7106), or Succimer (DMSA) (HY-B1768)^[3].
PDT-PAO (0.6-3.6 μM; 12-24 h) reduces the viability of NB4 cells in a concentration- and time-dependent manner, with incubation durations of 12 h or 24 h; pretreatment with 50 μM DL-Buthionine-(S,R)-sulfoximine (BSO) (HY-106376) enhances this cytotoxic effect^[3].
The combination of PDT-PAO (25-150 μM) with 4 μM Ca²⁺ induces swelling of isolated rat liver mitochondria in a concentration-dependent manner^[3].
PDT-PAO (50-200 μM) induces negligible H⁺ permeability of the mitochondrial inner membrane in isolated rat liver mitochondria, and only causes slight alterations in K⁺ permeability ^[3].
Incubation with PDT-PAO (100 μM; 30 min) for 30 min induces ultrastructural damage in isolated rat liver mitochondria^[3].