Cytotoxic and Apoptotic Properties of the Flavonoid-rich Ethyl Acetate Fraction of the Crude Methanol Leaf Extract of Syzygium samarangense (Blume) Merr. (Myrtaceae) against MCF-7 Breast Cancer Cells

Introduction@#Breast cancer is the most common cancer among women in the Philippines and about 3 in every 100 Filipina will be diagnosed with breast cancer in their lifetime. There is a need to discover safe, yet inexpensive herbal extracts with potential cytotoxic properties as potential treatment modalities to treat breast cancer. @*Objectives@#This study seeks to explore the cytotoxic and apoptotic properties of the ethyl acetate fraction of the defatted crude methanol leaf extract of Syzygium samarangense in MCF-7 breast cancer cell lines. @*Methods@#Screening for flavonoids of the extracts was performed using TLC, total flavonoids, total phenols, FTIR and LC-MS spectroscopy. The hydrogen peroxide and ferric reducing anti-oxidant power were used as substrates to assess in vitro anti-oxidative properties of the extracts. The MTT dye viability assay was used to assess the cytotoxic properties of the extracts against MCF-7 cells. Apoptotic properties of the extracts in MCF-7 cells were determined by caspase-3 activation assay, DNA fragmentation patterns and fluorescence microscopy after annexin-V and propidium iodide staining. @*Results@#The abundance of flavonoids in the ethyl acetate fraction of the crude methanol leaf extract was established by TLC, FTIR, LC-MS/MS, total flavonoid and total phenol analyses. The in vitro anti-oxidative properties of this extract was comparable to ascorbic acid. The median inhibitory concentration (IC50) of this extract in MCF-7 breast cancer cell lines was 7.2 mcg/mL while doxorubicin registered an IC50 of 1.2 mcg/mL. At this concentration, the extract was not cytotoxic to normally-dividing breast epithelial cells. Cytotoxicity of the extract was mediated via apoptosis as demonstrated by DNA fragmentation, caspase-3 activation and fluorescence microscopic analyses. @*Conclusion@#The study shows that the flavonoid-rich ethyl acetate fraction of the crude methanol leaf extract of S. samarangense possesses potent apoptotic and cytotoxic properties against MCF-7 breast cancer cell lines at low concentrations.

Cytotoxicity activity of geldanamycin derivatives against various cancer cell lines

Geldanamycin (1) was isolated as a major compound from Streptomyces zerumbet W14. It was then used as a precursor tosynthesize two new geldanamycins: 17-(tryptamine)-17-demethoxygeldanamycin (2) and 17-(5′-methoxytryptamine)-17-demethoxygeldanamycin (3). The cytotoxicity activity of these two new compounds was evaluated and comparedwith the cytotoxicity of compound 1. Cytotoxicity activity was evaluated against a normal cell line, and three cancercell lines using an 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colorimetric assay. Thesolubility of these compounds was also determined. The solubility of compounds 2 and 3 in water was 290.69and 348.18 µM, higher than that of compound 1 by about 1.91 and 2.29 times, respectively. Compounds 2 and 3showed moderate cytotoxic activity on Vero and human cervical carcinoma cells with IC50 values of >200.00 µg/ml. The strongest cytotoxicity of compound 3 was observed in human breast carcinoma cells (MCF-7) and humanhepatocellular carcinoma cell line (HepG2) cells with IC50 values of 82.50 and 114.35 µg/ml, respectively, while theIC50 values of compound 2 against MCF-7 and HepG2 cells were 105.62 and 124.57 µg/ml, respectively. The findingsshowed that these new geldanamycin derivatives exhibited selective cytotoxicity toward some cancer cells at a lowerconcentration. Therefore, future studies on these compounds could be useful for the management of some cancers

Functional and genomic characterization of three novel cell lines derived from a metastatic gallbladder cancer tumor

BACKGROUND: Gallbladder cancer (GBC) is the most common tumor of the biliary tract. The incidence of GBC shows a large geographic variability, being particularly frequent in Native American populations. In Chile, GBC represents the second cause of cancer-related death among women. We describe here the establishment of three novel cell lines derived from the ascitic fluid of a Chilean GBC patient, who presented 46% European, 36% Mapuche, 12% Aymara and 6% African ancestry. RESULTS: After immunocytochemical staining of the primary cell culture, we isolated and comprehensively characterized three independent clones (PUC-GBC1, PUC-GBC2 and PUC-GBC3) by short tandem repeat DNA profiling and RNA sequencing as well as karyotype, doubling time, chemosensitivity, in vitro migration capability and in vivo tumorigenicity assay. Primary culture cells showed high expression of CK7, CK19, CA 19-9, MUC1 and MUC16, and negative expression of mesothelial markers. The three isolated clones displayed an epithelial phenotype and an abnormal structure and number of chromosomes. RNA sequencing confirmed the increased expression of cytokeratin and mucin genes, and also of TP53 and ERBB2 with some differences among the three cells lines, and revealed a novel exonic mutation in NF1. The PUC-GBC3 clone was the most aggressive according to histopathological features and the tumorigenic capacity in NSG mice. CONCLUSIONS: The first cell lines established from a Chilean GBC patient represent a new model for studying GBC in patients of Native American descent.

Cytotoxic and Apoptotic properties of the Flavonoid-rich Ethyl Acetate fraction of the Crude Methanol Leaf Extract of Syzygium samarangense (Blume) Merr. (Myrtaceae) against MCF-7 Breast Cancer Cells

Introduction@#Breast cancer is the most common cancer among women in the Philippines and about 3 in every 100 Filipina will be diagnosed with breast cancer in their lifetime. There is a need to discover safe, yet inexpensive herbal extracts with potential cytotoxic properties as potential treatment modalities to treat breast cancer. @*Objectives@#This study seeks to explore the cytotoxic and apoptotic properties of the ethyl acetate fraction of the defatted crude methanol leaf extract of Syzygium samarangense in MCF-7 breast cancer cell lines. @*Methods@#Screening for flavonoids of the extracts was performed using TLC, total flavonoids, total phenols, FTIR and LC-MS spectroscopy. The hydrogen peroxide and ferric reducing anti-oxidant power were used as substrates to assess in vitro anti-oxidative properties of the extracts. The MTT dye viability assay was used to assess the cytotoxic properties of the extracts against MCF-7 cells. Apoptotic properties of the extracts in MCF-7 cells were determined by caspase-3 activation assay, DNA fragmentation patterns and fluorescence microscopy after annexin-V and propidium iodide staining. @*Results@#The abundance of flavonoids in the ethyl acetate fraction of the crude methanol leaf extract was established by TLC, FTIR, LC-MS/MS, total flavonoid and total phenol analyses. The in vitro anti-oxidative properties of this extract was comparable to ascorbic acid. The median inhibitory concentration (IC50) of this extract in MCF-7 breast cancer cell lines was 7.2 mcg/mL while doxorubicin registered an IC50 of 1.2 mcg/mL. At this concentration, the extract was not cytotoxic to normally-dividing breast epithelial cells. Cytotoxicity of the extract was mediated via apoptosis as demonstrated by DNA fragmentation, caspase-3 activation and fluorescence microscopic analyses. @*Conclusion@#The study shows that the flavonoid-rich ethyl acetate fraction of the crude methanol leaf extract of S. samarangense possesses potent apoptotic and cytotoxic properties against MCF-7 breast cancer cell lines at low concentrations.

Antiproliferative activity of longan (Dimocarpus longan Lour.) leaf extracts

Longan (Dimocarpus longan Lour.) belongs to Sapindaceae family. We examined the antiproliferative activity oflongan leaf extracts against cancer-derived cell cell lines in vitro. The tested samples were water extract, ethanolextract, n-hexane fraction, ethyl acetate fraction, and water fraction of longan leaf. Cytotoxicity test is against brineshrimps that was screened using Brine Shrimp Lethality Test. Antiproliferative activity assay on WEHI-164 cells(mouse fibrosarcoma cancer cell), THP-1 cells (human peripheral blood acute monocyte cell), and vero cells (noncancer or normal cell) that was conducted using hemocytometer with Trypan Blue Dye exclusion. The 50% lethalityconcentration (LC50) value of water extract, ethanol extract, n-hexane fraction, ethyl acetate fraction, and waterfraction were 854.64, 305.81, 446.55, 1313.44, and 1621.8 µg/ml. Ethanol extract exhibited significant cytotoxicdue to the lowest LC50 value. Ethanol extract was then used for further examination. The highest antiproliferativeactivity was achieved 44.93% by 600 µg/ml ethanol extract on WEHI-164 and 57.45% by 500 µg/ml ethanol extracton THP-1. It was significantly equal to doxorubicin antiproliferative activity. Ethanol extract dose had low effect tovero cells. This present study confirmed that the longan leaf ethanol extract possess marked antiproliferative activityon cancer-derived cell lines.

Evaluation of the cytotoxic effect of crude aqueous and ethanolic extracts isolated from Lentinus sp. on human cancer cell lines

Aims@#The aim of this study was to evaluate some chemical properties and the cytotoxic effect of aqueous and ethanolic crude polysaccharides extracted from five Lentinus sp. on human cancer cell lines. It was hypothesized that other species of the genus Lentinus could show the pharmacological actions as presence in Lentinus edodes, especially anticancer properties. @*Methodology and results@#Crude extracts of dried fruit bodies and mycelia from L. edodes, Lentinus sajor-caju, Lentinus swartzii, Lentinus squarrosulus and Lentinus velutinus were extracted using two solvents, hot water and 95% ethanol, and evaluated for their total carbohydrates, proteins, reducing sugar, phenol contents, and cytotoxicity. The yield of crude extracts was 33.6-205.3 mg/g dry weight of a sample. Cytotoxicity was determined with 10 mg/mL of crude aqueous and 1 mg/mL of crude ethanolic extracts by using the [3-(4,5-dimethylthiazol-2-yl)-2, 5- diphenyltetrazolium bromide] (MTT) method. All extracts showed non-cytotoxicity against the normal cell lines, LLC-MK2 and L929 cells. While, the extracts of L. edodes, L. sajor-caju, L. squarrosulus and L. velutinus displayed the cytotoxicity against the human cancer cell lines. @*Conclusion, significance and impact of study@#The crude aqueous and ethanolic extract from fruit bodies of L. velutinus and the ethanolic extract from fruit bodies of L. sajor-caju and L. squarrosulus displayed the adverse effect against the human cancer cell lines. Hence, these extracts are a potential source of bioactive compounds for cancer treatment.

Cytotoxic activity of abietane diterpenoids from roots of Salvia sahendica by HPLC-based activity profiling

ABSTRACT Screening of medicinal plants from Iranian flora against human cancer cell-lines have shown that an hexane extract from roots of Salvia sahendica Boiss. & Buhse, Lamiaceae, is active against human cervical cancer (HeLa) and colorectal adenocarcinoma (Caco-2) cell-lines at the test concentration of 100 µg/ml (100% inhibition). Cytotoxicity of the extract was localized with the aid of HPLC-time-based activity profiling adapted to the tetrazolium colorimetric bioassay. Four abietane-type diterpenoids in active time-windows were identified as cytotoxic compounds namely: sahandone (1), sahandol (2), 12-deoxy-salvipisone (3) and sahandinone (4). Compound 1 showed the highest toxicity against HeLa cells (IC50 = 5.6 ± 0.1 µg/ml), which was comparable with betulinic acid (IC50 = 4.3 ± 1.2 µg/ml), the positive control. Compound 2 was active against the HeLa cells (IC50 = 8.9 ± 0.7 µg/ml) but not the Caco-2 cell-line. Compounds 1, 3 and 4 exhibited moderate activity (IC50 = 22.9-41.4 µg/ml) against the Caco-2 cells. This study reveals that the HeLa cells are more sensitive to all tested compounds than the Caco-2 cells. In silico molecular docking study showed a rigid binding of the compounds to tyrosine kinase pp60src, and proved their cytotoxic activity.

Comparative untargeted proteomic analysis of ADME proteins and tumor antigens for tumor cell lines

In the present study, total membrane proteins from tumor cell lines including HepG2, Hep3B2, H226, Ovcar3 and N87 were extracted and digested with LysC and trypsin. The resulting peptide lysate were pre-fractionated and subjected to untargeted quantitative proteomics analysis using a high resolution mass spectrometer. The mass spectra were processed by the MaxQuant and the protein abundances were estimated using total peak area (TPA) method. A total of 6037 proteins were identified, and the analysis resulted in the identification of 2647 membrane proteins. Of those, tumor antigens and absorption, metabolism, disposition and elimination (ADME) proteins including UDP-glucuronosyltransferase, cytochrome P450, solute carriers and ATP-binding cassette transporters were detected and disclosed significant variations among the cell lines. The principal component analysis was performed for the cluster of cell lines. The results demonstrated that H226 is closely related with N87, while Hep3B2 aligned with HepG2. The protein cluster of Ovcar3 was apart from that of other cell lines investigated. By providing for the first time quantitative untargeted proteomics analysis, the results delineated the expression profiles of membrane proteins. These findings provided a useful resource for selecting targets of choice for anticancer therapy through advancing data obtained from preclinical tumor cell line models to clinical outcomes.

Effects of chemokine Fractalkine on proliferation and invasion of human pancreatic cancer cell lines by regulating IL-6/STAT3 signal pathway / 重庆医学

Objective To explore the effects of chemokine Fractalkine(FKN) on the proliferation and invasion of human pancreatic cancer cell lines PANC-1 and SW-1990 by regulating IL-6/STAT3 signal pathway.Methods Adenovirus served as the vector to construct and synthesizing FKN-small interfering RNA(siRNA),then which was transfected into PANC-1 and SW-1990.The proliferation and invasion ability of cells was determined by CCK-8 assay and Transwell assay.Expression of FKN,IL-6 and STAT3 protein and mRNA was detected by Western blot and RT-qPCR.Results After transfecting FKN-siRNA for 24 h,the absorbance values(A value) in the PANC-1 and SW-1990 groups had no significant changes,the A value at 48,72 h in the FKN-siRNA group was significantly higher than that in the control group and FKN-siRNA negative group (P＜0.05).After transfecting FKN-siRNA,the cellular invasive ability in the PANC-1 and SW-1990 FKN-siRNA group was significantly stronger than that in the control group and FKN-siRNA negative group(P＜0.05).After transfecting FKN-siRNA in cell lines PANC-1 and SW-1990,compared with the control group and FKN-siRNA negative group,the FKN protein and mRNA expression in the FKN-siRNA group was significantly decreased(P＜0.05),while IL-6 and STAT3 protein and mRNA expression was significantly increased(P＜0.05).Conclusion Chemokine FKN might play the inhibiting effect on the biological activity of pancreatic cancer cells by regulating IL-6/ STAT3 signal pathway.

Effects of chemokine Fractalkine on proliferation and invasion of human pancreatic cancer cell lines by regulating IL-6/STAT3 signal pathway / 重庆医学

Objective To explore the effects of chemokine Fractalkine(FKN) on the proliferation and invasion of human pancreatic cancer cell lines PANC-1 and SW-1990 by regulating IL-6/STAT3 signal pathway.Methods Adenovirus served as the vector to construct and synthesizing FKN-small interfering RNA(siRNA),then which was transfected into PANC-1 and SW-1990.The proliferation and invasion ability of cells was determined by CCK-8 assay and Transwell assay.Expression of FKN,IL-6 and STAT3 protein and mRNA was detected by Western blot and RT-qPCR.Results After transfecting FKN-siRNA for 24 h,the absorbance values(A value) in the PANC-1 and SW-1990 groups had no significant changes,the A value at 48,72 h in the FKN-siRNA group was significantly higher than that in the control group and FKN-siRNA negative group (P＜0.05).After transfecting FKN-siRNA,the cellular invasive ability in the PANC-1 and SW-1990 FKN-siRNA group was significantly stronger than that in the control group and FKN-siRNA negative group(P＜0.05).After transfecting FKN-siRNA in cell lines PANC-1 and SW-1990,compared with the control group and FKN-siRNA negative group,the FKN protein and mRNA expression in the FKN-siRNA group was significantly decreased(P＜0.05),while IL-6 and STAT3 protein and mRNA expression was significantly increased(P＜0.05).Conclusion Chemokine FKN might play the inhibiting effect on the biological activity of pancreatic cancer cells by regulating IL-6/ STAT3 signal pathway.

Flavonoids isolated from Sinopodophylli Fructus and their bioactivities against human breast cancer cells / 中国天然药物

Four prenylated flavonoids compounds 1-4, named sinopodophyllines A-D, and a flavonoid glycoside (compound 13), sinopodophylliside A, together with 19 known compounds (compounds 5-12 and 14-24) were isolated from the fruits of Sinopodophyllum hexandrum. The structures of new compounds were elucidated by extensive spectroscopic analysis, including HRESIMS, 1D and 2D NMR. Compounds 1-6, 9-11, and 14-17 were tested for their cytotoxicity against human breast-cancer T47D, MCF-7 and MDA-MB-231 cells in vitro, and compounds 2, 5, 6, 10 and 11 showed significant cytotoxicity (IC values < 10 μmol·L) against T47D cells.

Anti-proliferation effects of dammar-24-ene-3β-acetate-20S-ol on gastric cancer cells / 医学研究生学报

Objective Based on the previous research that the ethanolic extract from traditional Chinese medicine fructus forsythiae (Lianqiao) can obviously inhibit cancer cells in vitro, the article aimed to investigate the anti-proliferation effects of dammar-24-ene-3β-acetate-20S-ol (DM) extracted from fructus forsythiae on gastric cancer cells and its mechanism.Methods MTT assay was used to assess the anti-proliferation effects of DM on gastric cancer cells including SGC-7901, BGC-823, and MKN-45 in vitro.There were MKN-45 control group and its low dose and high dose groups, BGC-823 control group and its low dose and high dose groups, SGC-7901 control group and its low dose and high dose groups in the experiment.Flow cytometry was used to analyze the cell apoptosis rate.Cellquest software was used to analyze the results and record the ratio of cells at different cycles.DCFH-DA probe was applied to detect the ROS levels of blank control group, docetaxol group and DM group.The reaction system of microtubule assembly test was set with 10?mol/L docetaxol, 50 or 100 μmol/L DM final density and no medicine in blank control group.The readings of UV spectrophotometer were recorded.Microtubule assembly assay and microtubule immunofluorescence staining were applied to investigate the effects of DM on microtubule system.Results The inhibition ratio of 50 μg/L DM on the proliferation three gastric cell lines were all above 80%, with IC50s of MKN-45 11.72±1.35 μg/mL, BGC-823 17.19±0.82 μg/mL, SGC-7901 7.55±0.79 μg/mL.8 days′ low density culturing at 48 hours after 2 μg/mL DM treatment, compared with control group, the number of cell clones significantly reduced without much change in clone size, while 48 hours after 10 μg/mL DM treatment, besides a few clones of BGC-823, there were just several megascopic clones of SGC-7901 and MKN-45.In comparison with apoptotic cell ratio in MKN-45 control group[(21.1±2.5)%], its low dose group and high dose group resulted in significant rise of apoptotic cell ratio[(25.1±1.3)% and (55.2±2.3)%] (P0.05).In comparison with MKN-45 control group, the ratio of cells at S phase decreased in its low dose group[(14.5±2.7)% vs (12.3±3.3)%,P>0.05].In comparison with BGC-823 control group, the ratio of cells at S phase increased in its low dose group[(12.2±5.4)% vs (20.2±2.1)%,P<0.05].In comparison with SGC-7901 control group, the ratio of cells at S phase increased in its low dose group[(21.5±3.8)% vs (31.3±2.6)%,P<0.05].From the detection of intracellular active oxygen after DM treatment, dose-dependent ROS level increased in all three cell lines 48 hours after 10μg/mL and 50μg/mL DM treatment.From the results of microtubule immunofluorescence staining, 48 hours after the treatment of IC50 docetaxol and 10μg/mL DM, the fluorescence signals were in local concentration and disorder.Conclusion Dammar-24-ene-3β-acetate-20S-ol demonstrated anti-proliferation effects due to the apoptosis induced by cell cycle arrest at S phase.

Effect and mechanism of atorvastatin on cytotoxicity of human NK cells to colon cancer cells / 中国免疫学杂志

Objective:To explore the mechanism of the cytotoxicity of human NK cells induced by atorvastatin to colon cancer cell lines. Methods:After colon cancer cells (HCT-116,SW-480,Caco-2) were cultured with different concentrations of atorvastatin, CCK-8 assay was used to assess the effect of atorvastatin on growth of colon cancer cells. The amplification of human NK cells was induced by SCGM medium in vitro. Automatic biochemical analyzer was applied to test the cytotoxicity of NK cells to colon cancer cells which cultured with different concentration of atorvastatin. FCM was used to detect the expression rate of MICA/B on the cells. Results:(1) The cultivation of NK cells:The proportion of NK cells attained to 93. 1% from 4. 5% after cultured for 10 days. (2) The effects of atorvastatin on the growth of the colon cancer cells:After cultured with atorvastatin,the inhibition rate of HCT-116 cells was higher than that in control when the density of atorvastatin increased from 5 μmol/L to 40 μmol/L after 48 h and from 1. 25 μmol/L to 40 μmol/L after 96 h ( P<0. 05 ) . Correlation analysis showed that the concentration of atorvastatin and the growth inhibition rate of HCT-116 cells were positively correlated(r[48 h]=0. 13,r[96 h]=0. 22,P<0. 05). (3) The cytotoxicity of NK cells to colon cancer cells effected after atorvastatin: In different atorvastatin concentrations groups,the cytotoxicity of NK cells to three colon cancer cell lines was all higher than that in control ( P<0. 05 ) . The atorvastatin concentration was from 2. 5 μmol/L to 10 μmol/L for HCT-116 cells,from 5 μmol/L to 20μmol/L for SW-480 cells,and from 2. 5μmol/L to 20μmol/L for Caco-2 cells. Among the three cell lines, the cytotoxicity of NK cells to HCT116 was the highest in the same concentration. (4)NK cells by atorvastatin cutting statins 96 h,the concentration of 20 mmol/L and 40 mmol/L inhibition rate was higher than that of control group,more than other groups on NK cell growth without significant effect. ( 5 ) The impact of atorvastatin on MICA/B expression of colon cancer cells: After cultured with different concentrations of atorvastatin,the expression of MICA/B on colon cancer cells was higher than that in control(P<0. 05). The concentration was 2. 5μmol/L and 5μmol/L for HCT-116 cells,10μmol/L and 20μmol/L for SW-480 cells,and from 2. 5μmol/L to 40 μmol/L for Caco-2 cells. Conclusion:Atorvastatin could inhibit the growth of colon cancer cells (HCT-116,SW-480 and Caco-2) in a dose-dependent manner;and it could enhance the cytotoxicity of NK cells to colon cancer cells;it also could promote the expression of MICA/B of colon cancer cells,and improve the immunogenicity of colon cancer cells.

Inhibition of Garcinia Acid to Kidney Cancer Cell Lines via Wnt3α/β-catenin Signal Pathway / 中国药师

Objective:To investigate the mechanism in growth inhibition of garcinia acid to kidney cancer cell lines ( RC-2 ) . Methods:RC-2 cells were cultured in vitro, and garcinia acid at various concentrations was co-cultured with RC-2 cells. The antipro-liferative activities were determined by CCK-8 assay, the percentage of apoptosis was determined by flow cytometry analysis, and the expression levels of Survivin and related proteins in Wnt3α/β-catenin signal pathway were measured using Western Blot analysis. Re-sults:After the treatment with garcinia acid for 24h and 48h, the proliferation of RC-2 cells was significantly suppressed by garcinia acid in a dose-dependent manner, and all garcinia acid groups had significantly higher apoptosis percentage of RC-2 cells than the con-trol group. In G0/G1 period, RC-2 cells reduced while increased in G2/M period, and in S period, the cells remained the same a-mount. The expression levels of Survivin, Wnt3α and β-catenin decreased in RC-2 cells after the treatment with garcinia acid. Con-clusion:Garcinia acid can inhibit the proliferation and promote the apoptosis of RC-2 cells, and the mechanism may be related with the inhibition of Wnt3α/β-catenin signal pathway and further decreasing the expression levels of Survivin.

Inhibition effects of fungal immunomodulatory proteins from Ganoderma spp .on different gastric cancer cell lines in vit ro / 药学实践杂志

Objective To study the cell proliferative effects of fungal immunomodulatory proteins from Ganoderma spp . on 26 gastric cancer cell lines in vitro .Method 26 human gastric cancer cell lines were treated with FIPs by MTS assay .The average optical density (OD) in 490 nm and inhibition rate (GI50 )was counted by Universal Microplate Spectrophotometer . Results Three FIPs showed similar profiling in 26 human gastric cancer cell lines after 72 h treatment in cell proliferation as-say ,which except for NUGC-4 and OCUM-1 did not showed obvious anti-proliferative effect ,the other 24 human gastric cell lines showed some anti-proliferative effects ,especially for 7 cell lines(NUGC-3 ,GTL-16 ,HGC-27 ,IM95m ,SNU-638 ,SNU-216 and SNU-5) showing strong potency ,with their GI50 less than 50 μg/ml .Conclusion FIPs showed strong anti-prolifera-tive effects in some human gastric cancer cell lines in vitro ,which had potential to be further developed as anti-gastric cancer drugs .

Effects of 4 Flavonoids from Scutellaria Baicalensis on Different Cancer Cell Lines / 世界科学技术-中医药现代化

Wogonoside,wogonin,baicalin and baicalein are major chemical constituents of S.baicalensis.Baicalin,baicalein and wogonin have been reported previously to exert anti-cancer effects.The present study compared the anti-cancer effects of the four flavonoids individually towards four human cancer cell lines after 24-and 48-hour treatment based on cell viability assay.As a result,wogonin inhibited the growth of the four cell lines.The IC50 values after 48 hours of incubation were 97.9 μM for A549 lung adenocarcinoma cells,while 15.3 μM for HeLa cervical carcinoma cells,147 μM for HepG2 hepatocellular carcinoma cells and 104 μM for MCF-7 breast adenocarcinoma cells.In contrast,wogonoside,the glycoside of wogonin,showed no inhibitory effect against any one of the four cell lines.Baicalein inhibited the growth of HeLa cells,while baicalin inhibited the growth of HepG2 cells,both with higher IC50 values and less potent than wogonin.These findings established wogonin as the most active anti-cancer agent among the four major flavonoids of S.baicalensis.Since baicalin,the most abundant flavonoid in the herb,was found to enhance the growth of MCF-7 cells.Clinical applications of ingredients from S.baicalensis to the treatment of cancer should be carried out with purified compounds.

Bacillus spp. or Bacillus spp.-Derived Membrane Vesicles Induce the Intrinsic Pathways of Apoptosis of Human Colon Cancer Cell Lines

The striking increase in colorectal cancer (CRC) has shown the great fatality in Korea for more than 15 years. The leading edge of this rising incidence rate is mainly due to the people's dietary changes in Korea. Some studies have reported that the dietary fiber does not have significant cytotoxic effects on CRC cells, which contrasts to the effects of probiotics. It gives a positive evaluation that the nonpathogenic spore-forming Bacillus species among the probiotics including fermented bacteria might have optimistic effects on CRC incidence rate. Recently, we isolated Bacillus lentus (BL) from Korean soybean fermented food. BL showed the cytotoxic effect on human colon carcinoma cell lines HCT116 and SW480. Interestingly, BL did not have effect on human dermal fibroblast cells and human hepatoma cell line HepG2. It suggested that BL has the target cell-specific cytotoxicity toward human colon carcinoma cells. To clarify the death signaling pathway underlying the BL-induced apoptosis in cancer cells, we analyzed the expression of caspases, Bax and Bcl-2 by western blotting. The apoptotic effects by cytotoxic elements were executed by direct BL contact or membrane-derived vesicles isolated from BL. Treatment of HCT116 with BL activated caspase-9, -3 and increased cleavage form of poly (ADP-ribose) polymerase (PARP). However, caspase-8 activity was not increased by BL. BL-activated intrinsic pathway increased the pro-apoptotic Bax, decreased the anti-apoptotic Bcl-2 proteins on mitochondria, disrupted the mitochondrial membrane potential, and then released the cytochrome c from mitochondria. The membrane-derived vesicles (MVs) from BL induced apoptosis of the HCT116. Here, we propose that BL as a strong candidate for the development of apoptosis-specific anti-tumor agent will give great contribution to the understandings of the tumor-microbe interdisciplinary areas.

Single‑walled and multi‑walled carbon nanotubes based drug delivery system: Cancer therapy: A review.

Carbon nanotubes (CNTs) are advanced nano‑carrier for delivery of drugs especially anti‑cancer drugs. In the field of CNT‑based drug delivery system, both single‑walled carbon nanotubes (SWCNTs) and multi‑walled nanotubes (MWCNTs) can be used for targeting anticancer drugs in tissues and organs, where the high therapeutic effect is necessary. Benefits of the carbon nanotubes (CNTs) in drug delivery systems are; avoiding solvent usage and reducing the side effects. Therefore, the present review article described about achievement of SWCNTs and MWCNTs to deliver the anticancer drugs with different cancerous cell lines.

Potential of four marine-derived fungi extracts as anti-proliferative and cell death-inducing agents in seven human cancer cell lines

Objective: To evaluate the in vitro anticancer activity of crude ethyl acetate extracts of the culture of four marine-derived fungi Aspergillus similanensis KUFA 0013 (E1), Neosartorya paulistensis KUFC 7897 (E2), Neosartorya siamensis KUFA 0017 (E4) and Talaromyces trachyspermus KUFC 0021 (E3) on a panel of seven human cancer cell lines. Methods: Effects on cell proliferation, induction of DNA damage and cell death were assessed by MTT and clonogenic assays, comet assay and nuclear condensation assay, respectively. Results: The proliferation of HepG2, HCT116 and A375 cells decreased after incubation with the extracts E2 and E4. The anti-proliferative effect was confirmed by morphologic alterations and by clonogenic assay. Both extracts also induced cell death in HepG2 and HCT116 cells. Doxorubicin was used as a positive control and showed in vitro anticancer activity. Conclusions: This study demonstrated, for the first time, that extracts of Neosartorya paulistensis and Neosartorya siamensis have selective anti-proliferative and cell death activities in HepG2, HCT16 and A375 cells. The bioactivity of these extracts suggests a potential for biotechnological applications and substantiates that both should be further considered for the elucidation of the molecular targets and signal transduction pathways involved.

Effect and mechanism of rmhTNF on gastric cancer cell lines with differentΔ133p53 status / 中国癌症杂志

Background and purpose: Little about the function of p53 isoforms in gastric cancer was reported. This study was designed to explore the role ofΔ133p53 in the effect of recombinant mutant human tumor necrosis factor (rmhTNF) on gastric cancer cells, and provide a new basis for the diagnostics and therapeutics of gastric carcinoma. Methods: MKN45 (withΔ133p53 expression) or SGC7901 (withoutΔ133p53 expression) cells were treated with rmhTNF of different concentrations only or combined with 5-FU (a traditional gastric cancer cellular killer), and the growth inhibition rate and apoptosis was detected by CCK-8 and lfow cytometry. mRNA expressions ofΔ133p53, Gadd45αand CyclinB1 were measured by nested reverse transcription-polymerase chain reaction (nRT-PCR) or real-time polymerase chain reaction(RT-PCR). Results:On MKN-45 cells with positiveΔ133p53 expression, the inhibitory effect of rmhTNF was signiifcant, the inhibition rates of 50 and 500 IU/mL rmhTNF were 24.82%, 72.33%after culturing for 24 h (t=-9.558, P0.05). In apoptosis test, the apopto-sis-enhancing effect of rmhTNF was signiifcant on MKN45 cells, and the apoptosis-enhancing effect of 5-FU was fur-ther promoted signiifcantly by rmhTNF, the apoptosis of rmhTNF (50 IU/mL), rmhTNF (50 IU/mL) combined with 5-FU (25 μg/mL), rmhTNF (500 IU/mL) combined with 5-FU (25 μg/mL) were 18.20%, 48.66%, 59.83%, separately, after culturing for 24 h (F=123.931, P<0.05). In mRNA measurement, down-regulation ofΔ133p53 and CyclinB1, up-regula-tion of Gadd45αwere signiifcant in MKN45 cells treated by rmhTNF alone or combined with 5-FU. In nRT-PCR anal-ysis, the mRNA levels ofΔ133p53 were relatively 0.886, 0.499, 0.330, 0.161 (F=240.927, P<0.01);In real-time PCR analysis, the mRNA levels of Gadd45αwere 1.227, 1.694, 3.394, and the mRNA levels of CyclinB1 were 1.221, 0.722, 0.316, relatively. The expression ofΔ133p53 was positively related to CyclinB1 (r=0.977, P<0.01), but negatively re-lated to Gadd45α(r=-0.950, P<0.01). Conclusion:InΔ133p53 positively expressed MKN45 cells, rmhTNF showed as an effective tumor inhibitor and an enhancer of 5-FU as well, and this effect might be helped by two p53 down-stream molecules CyclinB1 and Gadd45α. The results suggest thatΔ133p53 might be a key target for the biological effect of rmhTNF against gastric cancer.