We designed and synthesized a 7-azaindole derivative（TH1082）, which was characterized by 1^H NMR and 13^C-NMR. We investigated its antitumor effects on human melanoma A375 cells, human liver cancer SMMC cells and human breast cancer MCF-7 cells in vitro via 3-（4,5-dimethyldiazol-2-yl）-2,5-diphenyl-tetrazolium bromide （MTT） assay and also explored the mechanism of antiproliferation of them. The results show that TH1082 significantly inhibited the proliferation of these cells to different extent. The IC50 values for A375 cells, SMMC cells and MCF-7 cells were 25.38, 48.70 and 76.94 μg/mL at 24 h, respectively. To observe cell morphological changes, acridine orange/ethidium bromide（AO/EB） staining and Hoechest33342/Pl staining were carried out. These results indicate that TH1082 could induced the apoptosis of A375 cells. The apoptotic rates were （9.5±2.09）%, （18.9±2.25）% and （39.5±2.02）%（5, 10 and 20 μg/mL） for A375, SMMC and MCF-7 cell lines, respectively. Further, we determined the activities of caspase-3 and caspase-9 in A375 cells treated with TH1082 at different concentrations（0, 5, 10 and 20 μg/mL） or Z-VAD-FMK（20 μmol/L）, a pan-caspase inhibitor for 24 h. The results show that TH1082 activated caspase-3 and caspase-9, and the activation could be blocked by Z-VAD-FMK. Taken together, these findings indicate that TH 1082 could inhibit the proliferation ofA375 cells via activating caspase-3 and caspase-9. 相似文献
A novel series of diaryl biuret derivatives containing a tetrazole moiety was designed and synthesized.All the target compounds were evaluated for their in vitro antitumor activity against HT-29,HepG2,MCF-7 and A549 cells by MTT assay.Most of them exhibited obvious antitumor activity,and four of them(4a,4c,4h and 7a)were superior to sorafenib in general.Among them,Compound 4h displayed more potent activity than sorafenib in all tested cancer cells.Compound 4c exhibited the most outstanding activity in inhibition of growth of HepG2 cells(IC50=0.55 μmol/L).Further,they both revealed favorable metabolic stability in in vitro assay.Compounds 4c and 4h are promising candidates for further development. 相似文献
A series of combretastatin A-4 based chalcones ( 14a-l ) were designed, synthesized and these compounds examined for inhibitory effects on the proliferation of human lung (A549), breast (MCF-7), melanoma (A375), and colon (HT-29) carcinoma cells. Compounds 14b , 14c , 14e , 14h , and 14i (tri/dimethoxy, methyl, and mono/dinitro derivatives) have exhibited the most potent antiproliferative activity with IC50 < 2 μM and the hexa methoxy derivative 14b , the most promising one, which displayed the potent inhibitory activities in MCF-7 (IC50: 10 nM), A375 (IC50: 12 nM), and A549 (IC50: 65 nM) cell lines, and is 18 times more potent than the CA-4. Compound 14b represents a new scaffold and the results provide insights into further development of anticancer agents. 相似文献
In this study we assessed the suitability of semiconducting P3OT thin films (30 nm) to sustain attachment, spreading, and proliferation of MC3T3‐E1 osteoblasts. Cell area correlated with surface wettability: area was larger on the more hydrophilic surface (TCPS) and lower on the more hydrophobic surface (P3OT). Cells were rounder, characterized by higher circularity values, on TCPS and Si compared to P3OT. P3OT proliferation rate at 24 h fell twofold after 48 h, then recovered at 72 h to a value significantly higher than that on TCPS. Presoaking experiments showed no evidence of cytotoxic effects or leachants from P3OT. Overall, we conclude that P3OT is a viable substrate for osteoblast attachment and proliferation.
Photodynamic therapy (PDT) using the second-generation photosensitizer phthalocyanine (Pc) 4 causes mitochondrial damage and induces apoptosis through the release of cytochrome c to the cytosol. Another protein of the mitochondrial intermembrane space, Smac/DIABLO (second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI), is also released to the cytosol in response to apoptotic stimuli and promotes caspase activation by binding IAP. To investigate the possible role of Smac/DIABLO in apoptosis induced by Pc 4-PDT, we transfected Smac/DIABLO (tagged at its C-terminus with green fluorescent protein [GFP]) into MCF-7c3 cells (human breast cancer MCF-7 cells stably transfected with procaspase-3) and DU-145 cells (human prostate cancer cells that express no Bax because of a frameshift insertion mutation). Confocal microscopy showed that recombinant Smac/DIABLO, like cytochrome c, localized to mitochondria and colocalized with MitoTracker Red. Three hours after exposure of MCF-7c3 cells to PDT (200 nM Pc 4 and 150 mJ/cm2 red light), Smac/DIABLO-GFP, as well as cytochrome c, was found largely in the cytosol. In contrast, for DU-145 cells, both Smac/DIABLO-GFP and cytochrome c remained in the mitochondria after PDT. By staining with Hoechst 33,342, typical apoptotic nuclei were observed in MCF-7c3 cells, but not in DU-145 cells, after Pc 4-PDT. These results suggest that the release of Smac/DIABLO from mitochondria may be regulated by a Bax-mediated mechanism and that Smac/DIABLO may cooperate with the cytochrome c-dependent apoptosis pathway. In addition, in MCF-7c3 cells transfected by Smac/DIABLO-GFP, apoptosis induced by Pc 4-PDT was greater than in cells transfected with the GFP vector alone or in untransfected cells, as determined by flow cytometry. Thus, Smac/DIABLO promotes apoptosis after Pc 4-PDT in a Bax-dependent manner and may facilitate the passage of PDT-treated cells through the late steps of apoptosis. 相似文献
The effect of doping P3OT with ferric chloride on the attachment and proliferation of MC3T3‐E1 osteoblasts is reported. Cell density and area correlated strongly with doping concentration: cells were larger and exhibited better spreading as doping increased. Cells cultured on undoped P3OT showed a decrease in proliferation between 24 and 48 h followed by a recovery after 72 h. However, this trend diminished with increasing doping concentration, and disappeared completely at the highest dopant level investigated. Analysis of cell‐cell spatial distributions suggested that contact inhibition of proliferation occurred similarly on both undoped and doped P3OT. From these results, FeCl3‐doping had no significant deleterious effect on attachment or proliferation of osteoblasts in vitro.
One new phenylpropanoid, turformosin A (1), and one new triterpene, turformosinic acid (2), together with 16 known compounds, were isolated from the stems of Turpinia formosana Nakai. All structures were elucidated on the basis of spectroscopic analysis, including 1D- and 2D-NMR techniques and MS analysis. Selected isolated compounds were evaluated for in vitro cytotoxicity against four human cancer cell lines and antioxidant scavenging effects on DPPH. (-)-(7'S,8'S)-threo-carolignan X (3) exhibited cytotoxicity against Hep2, WiDr, Daoy, and MCF-7 cell lines with ED(50) values of 3.60, 4.45, 6.07, and 13.7 μg/mL, respectively. Turformosin A (1), (-)-(7'S,8'S)- threo-carolignan X (3), methoxyhydroquinone-4-β-D-glucopyranoside (5), and methoxy-hydroquinone-1-β-D-glucopyranoside (6), exhibited similar anti-oxidative activity. Hep2 cells treated with 10 μg/mL of 3 showed elevation of sub-G1 population (from 20% at 8 h to 60% at 48 h), and activation of caspase-9/caspase-3/PARP cascade. Compound 3 induced intrinsic apoptotic pathway in Hep2 cells with dose and time dependence (10 μg/mL for 8 h). 相似文献
Microalgae is a rich source of polyunsaturated fatty acid. This study was conducted to identify and isolate microalgal strain with the potentials for producing polyunsaturated fatty acids (PUFAs) and determine its cytotoxic effect on some cancer cells. The algal strain (Chlorella sp. S14) was cultivated using modified BG-11 media, and algal biomass obtained was used for fatty acid extraction. Gas chromatographic–mass spectrometry was used to identify and quantify the levels of the fatty acid constituents. The total content of monounsaturated fatty acids (1.12%) was low compared to polyunsaturated fatty acids (PUFAs) (52.87%). Furthermore, n-3 PUFAs accounted for (12.37%) of total PUFAs with the presence of α-linolenic acid (2.16%) and cis-11,14,17-eicosatrienoic acid (2.16%). The PUFA-rich extract did not exhibit a cytotoxic effect on normal cells. Treatment with the PUFA-rich extract (150 µg/mL) significantly reduced cell viability in MCF-7 (31.58%) and A549 (62.56%) cells after the 48 h treatment. Furthermore, treatment of MCF-7 with fatty acid extracts (125 and 150 µg/mL) showed a significant reduction in MDA levels, increase in catalase activities and decrease in GSH level compared to untreated cells. However, a slight decrease in MDA level was observed in A549 cells after the 48 h treatment. There are no significant changes in catalase activities and GSH level in treated A549 cells. However, a slight reduction of NO levels was observed in treated MCF-7 and A549 cells. These results indicate the potentials of PUFA-rich extracts from Chlorella sp. S14 to reduce viability and modulate redox status in A549 and MCF-7 cells. 相似文献
AbstractIn this study, two novel benzimidazole-based N-heterocyclic carbene ligands (1a-b) and their silver(I) complexes (2a-b) were synthesized. All new compounds were characterized by FT-IR, LC-MS, 1H NMR, and 13C NMR spectroscopies. The in vitro antitumor activities of NHC ligands (1a-b) and their silver(I) complexes (2a-b) against DU-145 human prostate cancer cells, MDA-MB-231 and MCF-7 human breast cancer cells and L-929 (normal cells adipose from mouse) were also determined using MTT analysis for 24?h, 48?h, and 72?h. The results showed that while NHC ligands did not have in vitro antitumor activity on MCF-7, MDA-MB-231 and DU-145 cells, Ag(I)-NHC complexes have in vitro antitumor activities. The in vitro antitumor activity of 2a was found to be lower than that of 2b. Ag(I)-NHC complexes were observed to have higher IC50 values for non-cancerous cell lines than cancer cells. 相似文献
