Synthesis and antitumor activities of five Cu(II) complexes of bis(5-halosalicylidene)-1,3-propanediamine derivatives.

The development of metal complexes of Schiff base has attracted much attention due to their DNA binding properties and extensive biological activities. We reported here five copper(II) complexes [Cu(L1)] (1), [Cu(L2)] (2), [Cu(L3)] (3), [Cu2(L4)(OAc)] (4), and [Cu2(L5)(HCOO)] (5) bearing the bis-Schiff base ligands of bis(5-chlorosalicylidene)-1,3-propanediamine (H2L1), bis(5-chlorosalicylidene)-2-methyl-1,3-propanediamine (H2L2), bis(5-bromosalicylidene)-2-methyl-1,3-propanediamine (H2L3), bis(5-chlorosalicylidene)-2-hydroxyl-1,3-propanediamine (H3L4), and bis(5-bromosalicylidene)-2-hydroxyl-1,3-propanediamine (H3L5), respectively. The single crystal X-ray diffraction analysis results revealed that complexes 1-3 present mononuclear structures and complexes 4 and 5 show dinuclear structures. It was also shown that all of these complexes are stable under physiological conditions. The in vitro antitumor activities of the five complexes were evaluated. Anticancer selectivity was also found for complex 2 on different cell lines with the lowest IC50 value on Hela cells. Further mechanistic studies showed that the three mononuclear Cu(II) complexes can induce apoptosis through the mitochondrial pathway by decreasing mitochondrial membrane potential and increasing the reactive oxygen species (ROS) and Ca2+ levels. They can activate caspase-3 and caspase-9, and can also regulate the expression of pro-apoptotic protein and anti-apoptotic protein in cells. All of these results showed that complex 2 is a potential anticancer drug.

A ratiometric water-soluble fluorescent probe for the detection of sulfur dioxide derivative in sinusitis mice model.

Sulfur dioxide (SO2) plays an extremely important role in the basic processes of physiology and pathology. As an antioxidant, SO2 can maintain the redox homeostasis in the cell. Excessive inhalation of SO2 would lead to irreparable respiratory damage, resulting in respiratory diseases, neurological disorders, and even cardiovascular disease. Thus, it is urgent to exploit an excellent way to monitor SO2 derivatives in biological system. Herein, we design a water-soluble ratiometric fluorescent probe to fast detect the level of SO2 derivatives in living cells in vivo. The probe displays obvious fluorescence signal at long wavelength, which is helpful for imaging of biological system. After respond to SO2 derivatives, the fluorescence signal at 465 nm increases rapidly due to the Michael addition reaction is triggered, further causing the disruption of large conjugated system. The probe exhibits high selectivity and fast respond to SO2 derivatives, which can be able to sensitive and real-time monitoring of SO2 derivatives level in living cells. Moreover, the probe reveals a low detection limit and a great linear relationship to SO2 derivatives. Based on the negligible cytotoxicity and good biocompatibility of the probe, which is employed to detect exogenous and endogenous SO2 derivatives in living cells. In addition, it is also served as a potential chemical tool to detect SO2 derivatives in mice model of sinusitis.

Antitumor Activities for Two Pt(II) Complexes of Tropolone and 8-Hydroxyquinoline Derivative.

The reactions of cis-Pt(DMSO)2Cl2 and tropolone (HL) with 8-hydroxyquinoline (HQ) or 2-methyl-8-hydroxyquinoline (HMQ) gave [Pt(Q)(L)] (1) and [Pt(MQ)(L)] (2), which present mononuclear structures with their Pt(II) ions four-coordinated in square planar geometries. Their in vitro biological properties were evaluated by MTT assay, which showed a remarkable cytotoxic activity on the cancer cell lines. 1 shows higher cytotoxic activities on tumor cells such as T24, HeLa, A549, and NCI-H460 than complex 2 and cisplatin, with IC50 values <16 µM. Among them, an IC50 value of 3.6 ± 0.63 µM was found for complex 1 against T24 cells. It presented a tuning cytotoxic activity by substitution groups on 8-hydroxyquinoline skeleton. In our case, the substitution groups of -H are much superior to -CH3 against tumor cells. It revealed that both complexes can induce cell apoptosis by decreasing the potential of a mitochondrial membrane, enhancing reactive oxygen species and increasing Ca2+ levels of T24 cells. The T24 cell cycle can be arrested at G2 and G1 phases by complexes 1 and 2, respectively, with an upregulation for P21 and P27 expression levels and a down-regulation for cyclin A, CDK1, Cdc25A, and cyclin B expression levels. Furthermore, complex 1 exhibits satisfactory in vivo antitumor activity as revealed by the tumor inhibitory rate and the tumor weight change as well as by the cute toxicity assay and renal pathological examinations, which is close to cisplatin and much better than complex 2. All of these suggest that 1 might be a potential candidate for developing into a safe and effective anticancer agent.

Effect of pH on the isolation of urinary exosome.

PURPOSE: Urinary exosome is an ideal noninvasive, low-cost source of kidney diseases biomarkers. However, many factors effect the isolation of urine-derived exosome. The effect of pH on the yield of exosome isolation under different pH was explored. METHODS: The pH was adjusted for 4, 5, 6, 7 and 8 with hydrochloric acid and sodium hydroxide solution. All samples were incubated for 30 min before differential ultracentrifugation. Exosome-associated protein markers TSG101, ALIX and total concentration of RNA were evaluated by Western-blotting and micro-amount ultraviolet spectrophotometer, respectively. RESULTS: A major loss of urinary exosome was received at pH 8 compared with alkali medium or control group. There was no difference whether or not added EDTA-Na2. CONCLUSIONS: Acidic environment was likely to conducive to the isolation of exosome and maintain its stability and integrity that suggest pH medium needs to be carefully considered and also provide a methodology for future separation exosome.

Genistein and beta-carotene enhance the growth-inhibitory effect of trichostatin A in A549 cells.

BACKGROUND: The combination of anti-cancer drugs with nutritional factors is a potential strategy for improving the efficacy and decreasing the toxicity of chemotherapy. However, whether nutritional factors enhance the effect of trichostatin A (TSA), a novel anti-cancer drug, is unclear. AIM: We investigated the individual enhancing effect and its possible mechanisms of genistein, daidzein, beta-carotene, retinoic acid, and alpha-tocopherol on the cell-growth-inhibitory effect of TSA in a human lung carcinoma cell line, A549. METHODS: A549 cells were incubated with TSA (50 ng/mL) alone or in combination with the various nutritional factors for various times, and cell growth was measured. IMR90 cells, human lung fibroblasts, were also incubated with TSA alone or in combination with genistein or beta-carotene to determine the selectivity of these treatments. In addition, we studied effects on the cell cycle, caspase-3 activity, and DNA damage (by comet assay) in A549 cells. RESULTS: After treatment for 72 h, 10-microM genistein or beta-carotene significantly enhanced the growth-inhibitory effect of TSA in A549 cells. Daidzein, retinoic acid, and alpha-tocopherol at the same concentration had no significant effect. However, genistein and beta-carotene failed to enhance the cell-growth-arrest effect of TSA in IMR90 cells. Flow cytometric analysis showed that both genistein and beta-carotene significantly increased the TSA-induced apoptosis in A549 cells. Genistein significantly enhanced TSA-induced caspase-3 activity in A549 cells by 34% at 24 h, and the caspase-3 inhibitor partly inhibited the enhancing effect of genistein on TSA-induced apoptosis. beta-Carotene did not significantly affect TSA-induced caspase-3 activity. However, beta-carotene rather than genistein enhanced TSA-induced DNA damage. CONCLUSIONS: Genistein and beta-carotene enhance the cell-growth-arrest effect of TSA on A549 cells. Genistein exerts its effect, at least partly, by increasing caspase-3 activity; whereas beta-carotene may enhance TSA-induced cell death mainly through a caspase-3-independent pathway.