Anti-Tumor Effects Of Zinc Complexe Of The 2-Benzene-Pyridine Thiosemicarbazone

Objective: To investigate the potent inhibitor of Zinc Complexe of Benzene-pyridine thiosemicarbazone on the K562(a human leucocythemia cancer cell line) cells,in a dose- and time-dependent manner.Methods: Different dose of BT-zinc were used to induce the cytotoxicity in K562 cells in order to optimize dose by MTT assay and the growth curve. Observe the 2-benzoylpyridine thiosemicarbazone's proliferation effect in vitro on chang liver cells through MTT assay and investigate the anti-tumor activity and selectivity of Zinc Complexe of 2-benzoylpyridine thiosemicarbazone in vitro. DNA-binding dye Acridine Orange/ Ethidium Bromide (AO/EB) was used to determine the morphological characteristic of apoptotic cells. Mitochondrial membrane potential in K562 cells were monitored by the high content screening (HCS) combining with Rh123.PI/Hochest 33342 was used to a signature of cell membrane integrity and cell damage. Fura-2/AM was employed to detect intracellular Ca²⁺ concentration ([Ca²⁺]i) as a cell permeable fluorescent probe.Results: 1. After treatment with 0.1μM, 1μM, 10μM, 30μM, 50μM BT-zinc in K562 cells for 48 hours, the cell viability decreased markedly, while at concentration (0.1μM) could inhibit the cell viability obviously. 2. When acting on K562 cells 48h by BT-zinc, IC₅₀ is 13.93μM. The cell growth curve shows that the proliferation of K562 cells inhibited by BT-zinc. 3. From observing the morphological characteristics of K562 cells by AO/EB staining, the results show that BT-zinc can promote apoptosis of K562 cells, cause the typical morphological features of apoptosis. Fluorescent dye by measuring the intracellular fluorescence intensity of PI and hochest33342 can reflect the degree of cell damage and necrosis; By measuring the intracellular fluorescent dye rhodamine 123 (Rh123) fluorescence intensity reflects the changes in mitochondrial membrane potential, different concentrations of BT-zinc could significantly inhibit the combined K562 cells decreased the level of mitochondrial membrane potential; Through detecting intracellular free Ca²⁺ concentration showed that the BT-zinc caused a significant K562 cell Ca²⁺ overload.Conclusions: The new compound BT-zinc can cause significant damage and apoptosis in K562 cells, and the effect is showed the dose-dependent and time-dependent.BT-zinc may also represent a potential treatment strategy for anti-tumor.