Parthenolide induces apoptosis and cell cycle arrest of human 5637 bladder cancer cells in vitro

Parthenolide, the principal component of sesquiterpene lactones present in medical plants such as feverfew (Tanacetum parthenium), has been reported to have anti-tumor activity. In this study, we evaluated the therapeutic potential of parthenolide against bladder cancer and its mechanism of action. Treatment of bladder cancer cells with parthenolide resulted in a significant decrease in cell viability. Parthenolide induced apoptosis through the modulation of Bcl-2 family proteins and poly (ADP-ribose) polymerase degradation. Treatment with parthenolide led to G1 phase cell cycle arrest in 5637 cells by modulation of cyclin D1 and phosphorylated cyclin-dependent kinase 2. Parthenolide also inhibited the invasive ability of bladder cancer cells. These findings suggest that parthenolide could be a novel therapeutic agent for treatment of bladder cancer.     

Synthesis, crystal structure and in vitro antitumor activity of a novel organotin(IV) complex with 9-hexyl-9H-carbazole-3-carboxylic acid

9-Hexyl-9H-carbazole-3-carboxylic acid (LCOOH) and its complex with Ph₃Sn(OH), [Ph₃SnO₂CL] (I), were synthesized. The structure of complex I was solved by single-crystal X-ray diffraction determination, indicating that I shows the discrete framework. Furthermore, this complex was tested in vitro for its cytotoxic activity, using human hepatocellular carcinoma cell line (BEL-7402) and human hepatocellular liver carcinoma cell line (HepG2); 5-fluorouracil was used as a positive control substance. This complex showed cytotoxicity greater than that of 5-fluorouracil.     

Synthesis, crystal structure, and in vitro antitumor activity of a novel tetranuclear Di-n-butyltin(IV)

A di-n-butyltin(IV) complex with (E)-3-(4-(9H-carbazole-9-yl)phenyl) acrylic acid (HL) of the formula {[n-Bu₂SnOL]₂O}₂ was synthesized and characterized by X-ray crystallography. This complex is a tetranuclear one with ladder framework. Furthermore, this complex was tested in vitro for its cytotoxic activity, using human hepatocellular carcinoma cell line (BEL-7402) and human hepatocellular liver carcinoma cell line (HepG2); 5-Fluorouracil was used as a positive control substance. This complex showed cytotoxicity greater than that of 5-Fluorouracil.     

Novel Bradykinin Receptor Inhibitors Inhibit Proliferation and Promote the Apoptosis of Hepatocellular Carcinoma Cells by Inhibiting the ERK Pathway

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Studies have shown that bradykinin (BK) is highly expressed in liver cancer. We designed the novel BK receptor inhibitors J051-71 and J051-105, which reduced the viability of liver cancer cells and inhibited the formation of cancer cell colonies. J051-71 and J051-105 reduced cell proliferation and induced apoptosis in HepG2 and BEL-7402 cells, which may be due to the inhibition of the extracellular regulated protein kinase (ERK) signaling pathway. In addition, these BK receptor inhibitors reversed the cell proliferation induced by BK in HepG2 and BEL-7402 cells by downregulating B1 receptor expression. Inhibiting B1 receptor expression decreased the protein levels of p-ERK and reduced the malignant progression of HCC, providing a potential target for HCC therapy.     

Efficient Synthesis and Antitumor Activities of Indioside E Analogs

An efficient synthesis of seven analogs of a naturally occurring saponin, indioside E, is described. The synthesis used a 3,4,6-O-protected D-galactopyranosyl thioglycoside as the key intermediate to enable regioselective glycosylation and one-pot multistep reactions. Antitumor activities of the synthetic saponins against a human hepatocellular carcinoma cell line BEL-7402 and a human breast adenocarcinoma cell line MCF-7 were evaluated by means of the CCK-8 assay. Analogs carrying trisaccharides with the D-xylopyranose in indioside E substituted with a D-ribopyranose and an L-arabinopyranose or with its diosgenin aglycon replaced with tigogenin exhibited similar antitumor activities as indioside E, but not other analogs.     

支链/环链烷氧基乙酸为离去配体的铂(Ⅱ)配合物的体外活性研究

合成了12个带支链/环链烷氧基乙酸为离去基团的顺铂类配合物,通过元素分析、红外光谱、核磁共振氢谱和质谱对配合物进行了表征。研究了所有化合物对人非小细胞肺癌A549、人肝癌细胞BEL-7402和人乳腺癌细胞MCF-7细胞系的体外抗肿瘤活性。测试结果表明,12个配合物中有5个对人乳腺癌细胞系MCF-7有较好的体外活性。其中化合物2(顺-二(异丙氧基乙酸根)·二氨合铂(Ⅱ))在所有的化合物中显示最高的活性,对所测3个细胞系都是如此。     

A novel chalcone derivative from Onychium japonicum

A novel chalcone derivative was isolated from Onychium japonicum and its structure was elucidated by spectroscopic methods. The isolated compound showed cytotoxic activity against the human carcinoma cell lines Hela and BEL-7402 in vitro.     

Synthesis,Crystal Structure and Antitumor Activity of Mixed Ligand Coordination Compound of Copper with Norfloxacin and 1,10-Phen,[Cu(NFLX)(phen)(H_2O)] NO_3·3H_2O

Fluoroquinolones are the widely used antibiotics for treating of numerous diseases1-4. Norfloxacin(1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-1,4dihydroquinoline-3-carboxylicacid, NFLX) is a typical member of this family and its metal coordination compounds have also received much more attention5-11. Apart from the synthesis and physicochemical properties of the coordination compounds, their antibacterial properties were also tested7-13, but there was scare report on antitumor properties of th…     

MTT法测定稀土离子对BEL-7402及K562细胞的毒性及增殖毒性

用MTT法测定稀土离子在不同浓度、不同培养液中,与BEL 7402和K562细胞作用不同时间,对细胞的毒性和增殖毒性。结果表明,在含10%小牛血清培养液中,仅个别稀土离子在较高浓度时对BEL 7402细胞增殖有较弱的抑制作用;对于K562细胞,稀土离子在低浓度时对细胞增殖即表现出较强的抑制作用(P<0.05)。当培养液不含小牛血清时,较低浓度的稀土离子即可抑制BEL 7402细胞的增殖(P<0 05)。     

Inhibitory Effects of Mistletoe Alkali on Salivary Adenoid Cystic Carcinoma Cells

Mistletoe alkali plays an important role in salivary adenoid cystic carcinoma(SACC) cell proliferation, apoptosis and invasion. Mistletoe alkali shows potent anticaner property. In this paper,immunocytochemical and immunofluorescence staining were employed to evaluate the expression levels of proliferating cell nuclear antigen(PCNA), Caspase 3, Caspase 8 and Caspase 9. Apoptosis was detected by acridine orange/ethidium bromide (AO/EB) staining, cell invasion ability was assessed by Boyden Chamber assay. Pretreatment with mistletoe alkali markedly decreased PCNA expression in SACC cells in a dose-dependent manner(P<0.001) and also led to increase the expression of Caspase 3, Caspase 8 and Caspase 9 in SACC cells compared with control group(P<0.001). Number of apoptotic cells increased dramatically in mistletoe alkali group(P<0.001). In Boyden Chamber assay, mistletoe alkali treatment could inhibit SACC cells to penetrate the artificial basement membrane compared with control group(P<0.01). Mistletoe alkali remarkably inhibited the proliferation and invasion of SACC cells and induced the apoptosis of SACC cells. These results provide an insight into the mechanisms of anticancer effects of mistletoe alkali, and highlight the potential clinical application of it.     

Cytotoxicity, cellular uptake, cell cycle arrest, apoptosis, reactive oxygen species and DNA-binding studies of ruthenium(II) complexes

Three ruthenium(II) polypyridyl complexes [Ru(dmb)₂(dadppz)]²⁺ 1, [Ru(bpy)₂(dadppz)]²⁺ 2 and [Ru(phen)₂(dadppz)]²⁺ 3 were synthesized and characterized by elemental analysis, ES-MS, ¹H NMR and ¹³C NMR. Their DNA-binding behaviors were investigated by absorption titration, fluorescence spectroscopy and viscosity measurements. Cytotoxicity in vitro, apoptosis, cell cycle arrest, cellular uptake and reactive oxygen species assays were performed. The complexes were found to show moderate DNA-binding affinities and high cytotoxicities toward A549, BEL-7402, MG-63 and SKBR-3 cell lines. These complexes can effectively induce apoptosis of BEL-7402. In cell cycle assays, the complexes induced S-phase arrest on BEL-7402 cells and G0/G1-phase arrest on SKBR-3 cells. The DNA-binding experiments showed that the three complexes interact with CT-DNA through an intercalative mode.     

Two novel alkaloids from the stem of Saprosma hainanense and their cytotoxic activities in vitro

Two novel alkaloids, saprosmine A (1) and saprosmine B (2), were isolated from the stem of Saprosma hainanense MERR., along with five known alkaloids: marcanine A (3); cleistopholine (4); 4-methoxycarbonyl-5,10-benzogquinolinequinone (5); liriodenine (6); and quinoline (7). The chemical structures were established on the basis of extensive spectroscopic (IR, 1D-NMR, 2D-NMR, MS) data analysis and by comparison with spectroscopic data reported in the literature. Compounds 1 to 6 were evaluated for in vitro cytotoxic activities against the SPC-A-1 (human lung cancer), BEL-7402 (human hepatocellular carcinoma), SGC-7901 (human gastric cancer), and K-562 (human myelogenous leukaemia) cancer cell lines. Compounds 1 and 2 exhibited weak cytotoxic activities against K-562 cells. Compounds 3 and 5 showed cytotoxic activities against all four cancer cell lines.     

New hydrophilic/lipophilic tetra-α-(4-carboxyphenoxy) phthalocyanine zinc-mediated photodynamic therapy inhibits the proliferation of human hepatocellular carcinoma Bel-7402 cells by triggering apoptosis and arresting cell cycle

Photodynamic therapy (PDT) is a novel and promising antitumor treatment. Phthalocyanine-mediated PDT has shown antitumor activity in some tumor cells, but the effect of new hydrophilic/lipophilic tetra-α-(4-carboxyphenoxy)phthalocyanine zinc (TαPcZn)-mediated PDT (TαPcZn-PDT) on human hepatocellular carcinoma Bel-7402 cells and underlying mechanisms have not been clarified. In the present study, therefore, the ultraviolet-visible (UV-vis) absorption spectrum and cellular localization of TαPcZn, and effect of TαPcZn-PDT on the proliferation, apoptosis, cell cycle, Bcl-2 and Fas in Bel-7402 cells were investigated by spectrophotometry, inverted microscope, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, electron microscopy, annexinV-FITC/propidium iodide double staining, DNA content and immunoblot assay, respectively. We found that an intense absorption in UV-vis absorption spectrum of TαPcZn was in the red visible region at 650-680 nm, where light penetration in tissue is efficient, that green TαPcZn localized to both plasma membrane and nuclear membrane of Bel-7402 cells, signifying that there was a selective uptake of TαPcZn in Bel-7402 cells and TαPcZn-PDT would be expected to directly damage DNA, and that TαPcZn-PDT significantly resulted in the proliferation inhibition, apoptosis induction, S cell cycle arrest, and down-regulation of Bcl-2 and Fas. Taken together, we conclude that TαPcZn-PDT inhibits the proliferation of Bel-7402 cells by triggering apoptosis and arresting the cell cycle.     

Synthesis,biological activities studies of ruthenium(II) polypyridyl complexes

Four ruthenium(II) polypyridyl complexes were synthesized and characterized by elemental analysis, IR, ESI-MS and ¹H NMR. The in vitro cytotoxicities of the complexes against BEL-7402, HeLa, A549, HepG2 and MG-63 cancer cells were investigated by MTT methods, giving IC₅₀ values ranging from 6.9 to 43.5 μM. The complexes show their highest inhibitory effect on MG-63 cells, but no cytotoxic activities against HeLa cells. Cellular uptake experiments indicate that the complexes can enter the cytoplasm and accumulate in the cell nuclei. The complexes can induce apoptosis in MG-63 cells, enhance the levels of reactive oxygen species, and induce a decrease in mitochondrial membrane potential. The cell cycle distribution shows that the complexes induce cell cycle arrest at S phase in MG-63 cells. Additionally, these complexes can up-regulate the levels of Bad and Bid expression and down-regulate the expression of Bcl-2 and Bcl-x.     

Inhibition of Salidroside on Salivary Gland Adenoid Cystic Carcinoma

To evaluate the role of salidroside on proliferation,apoptosis and invasiveness of salivary gland adenoid cystic carcinoma cells(SACC),immunocytochemical staining was employed to detect proliferating cell nuclear antigen(PCNA),caspase 3 and caspase 8 expression in SACC-2 cells.Modified Boyden chamber assay combined with laser confocal microscopy(LSCM) was used to evaluate the invasion and migration abilities of SACC-2 cells at different time point.Immunohistochemistry staining revealed that the expression of PCNA was significantly decreased(P0.01) after salidroside treatment.In contrast,salidroside treatment led to increased caspase 3 and caspase 8 in SACC-2 cells.Cell migration depth and number of cells that penetrated Boyden chamber were also decreased by salidroside.Salidroside potently inhibits the proliferation and simultaneously induces the apoptosis of SACC-2 cells.Migration and invasion of SACC-2 cells are also inhibited.Our data throw light on potential clinical application of salidroside to the patients with SACC.     

Two new antitumor diterpenes from Pinus sylvestris

Two new diterpenes, 15-ethyl-18-methyl pinifolate （1） and 18-hydroxy-labda-8（17）, 13E-dien-15-acetate （2）, were isolated from the needles of Pinus sylvestris. Their structures were elucidated by spectroscopic methods, including 2D-NMR spectra. Compound 1 exhibited the significant cytotoxic activity against the human carcinoma cell lines Hela, SK-N-SH and BEL-7402 in vitro.     

Synthesis,characterization and in vitro antitumor behavior of a vanadium(V) complex with 4′-(3-methoxyphenyl)-2,2′:6′2″-terpyridine

A dioxovanadium(V) complex, [VO₂(moptpy)](ClO₄) (1, moptpy = 4′-(3-methoxyphenyl)2,2′:6′2″-terpyridine), was synthesized and characterized by elemental analysis, ESI-MS, UV–vis, IR, and ¹H, ¹³C, and ⁵¹V NMR. The cytotoxicity in vitro of 1 was evaluated against cancer cell lines HepG-2 (hepatocellular carcinoma), SGC-7901 (gastric carcinoma), SiHa (cervical cancer), BEL-7402 (hepatocellular), and rat PC-12 (pheochromocytoma) by the MTT method. The results demonstrated that 1 exhibits superior anticancer activity in vitro with much lower values of 50% inhibitive concentration (IC₅₀) against the selected cell lines than cisplatin, and 1 shows the highest cytotoxic activity toward SGC-7901 cells (IC₅₀ = 1.3 ± 0.1 μM) among the selected cell lines. A series of cellular morphological and staining experiments were carried out, and the results indicated that 1 can effectively induce apoptosis of SGC-7901 cells through a ROS-mediated mitochondrial dysfunction pathway. In addition, cellular incorporation and cell cycle analysis were also performed, and it was concluded from the experimental observations that 1 can efficiently enter into the cell nuclei, and the complex inhibits cell growth in SGC-7901 cell at G0/G1 phase.     

A triterpenoid from Thalictrum fortunei induces apoptosis in BEL-7402 cells through the P53-induced apoptosis pathway

Thalictrum fortunei S. Moore, a perennial plant distributed in the southeastern part of China, has been used in Traditional Chinese Medicine for thousands of years for its antitumor, antibacterial and immunoregulatory effects. In order to investigate the active components and the mechanism of the anti-tumor effects of Thalictrum fortunei, the growth inhibitory effects of eight triterpenoids isolated from the aerial parts of the plant on tumor cell lines were examined by 3-(4,5)-dimethylthiazoy1-3,5-diphenyltetrazolium bromide (MTT) assay. The MTT-assay results showed that the inhibitory activity of 3-O-β-D-glucopyranosyl-(1→4)-β-D-fucopyranosyl(22S,24Z)-cycloart-24-en-3β,22,26-triol 26-O-β-D-glucopyranoside (1) was stronger than that of the other seven tested triterpenoids on human hepatoma Bel-7402 cell line (Bel-7402), human colon lovo cells (LoVo), human non-small cells lung cancer NCIH-460 cells (NCIH-460) and human gastric carcinoma SGC-7901 cells (SGC-7901) after 48 h treatment in vitro, with the IC(50) values of 66.4, 84.8, 73.5, 89.6 μM, respectively. Moreover, the antitumor mechanism of compound 1 on Bel-7402 cell was explored through nucleus dyeing, fluorescence assay, flow cytometry and western blot. The flow cytometric analysis results revealed that compound 1 caused apoptosis and mitochondrial membrane potential (MMP) loss in Bel-7402 cells. A fluorescence assay indicated that intracellular reactive oxygen species (ROS) were markedly provoked by compound 1 treatment compared to control cells. Immunoblot results showed that compound 1 significantly increased the expression levels of cleaved caspase-3, P53 and Bax protein, and decreased the expression level of Bcl-2 protein. These findings indicate that compound 1 inhibits the growth activity of tumor cells, probably through the P53 protein-induced apoptosis pathway.     

Synthesis and antitumor activity of 6- and 2- （ 1-acyl sulfanylalkyl）-5,8-dimethoxy- 1,4-naphthoquinones

Sixteen novel 6- and 2-（1-acylsulfanylalkyl）-5,8-dimethoxy-l,4-naphthoquinones were designed and synthesized. Their cytotoxicities were evaluated in vitro against BEL-7402, HT-29 and SPC-Al cell lines. The pharmacological results showed that most of the prepared compounds displayed the excellent selectivity for HT-29 cell line. Compound lab exhibited the most potent antitumor activity among the tested compounds.     

Apoptosis in BEL-7402 cells induced by ruthenium(II) complexes through a ROS-mediated mitochondrial pathway

Three Ru(II) polypyridyl complexes [Ru(dmb)₂(HMSPIP)](ClO₄)₂ (1), [Ru(phen)₂(HMSPIP)](ClO₄)₂ (2) and [Ru(dmp)₂(HMSPIP)](ClO₄)₂ (3) were synthesized and characterized. The cytotoxicity in vitro, apoptosis, cell cycle arrest, reactive oxygen species and mitochondrial membrane potential were assayed. The IC₅₀ values of complexes 1, 2 and 3 toward BEL-7402, A549, MG-63 and SK-BR-3 cell lines ranged from 10.9 ± 1.6 to 42.0 ± 3.4 μM. Complexes 1, 2 and 3 can effectively induce apoptosis and inhibit the growth of BEL-7402 cells at the G2/M phase. These complexes can enhance the level of reactive oxygen species and induce decrease in the mitochondrial membrane potential. Additionally, complex 2 can down-regulate the expression of antiapoptotic protein of Bcl-2 protein and up-regulate the levels of proapoptotic protein Bim in BEL-7402 cells.