Growth Inhibition Of MCF-7 Cells Research Articles

Antioxidant and Anticancer Activity of Pericarp Water Extracts of Mediterranean Ancient Chestnut Accessions

The residue of chestnut processing generates a large amount of waste material, a resource not adequately exploited. The antioxidant and antitumoral properties of cold and hot water extracts from discarded pericarp of four chestnut Sardinian accessions and one marron variety were studied. The antioxidant capacity of the extracts was determined by spectrophotometric and electrochemical tests. The 1,1-diphenyl-2-pic-rylhydrazyl (DPPH) and 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) results were highly correlated with each other; likewise, a good correlation was found between Ferric Reducing Antioxidant Power (FRAP) and cyclic voltammetry (CV) values, both based on the direct transfer of electrons. The antiproliferative effect on normal cells (fibroblasts), and on colon (RKO and SW48) and breast (MCF7) cancer cells was evaluated. Additionally, this paper marks the first application of chestnut extracts to investigate their effects on melanoma (B16F10) cells. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test demonstrated that temperature and different extraction times significantly influenced the growth of cells, both normal and tumor. The fibroblast growth was significantly inhibited by moderate doses of cold extracts, while the GI50 values calculated for hot extracts were high, regardless of the accession or cultivar. An even more marked inhibitory action of the cold extracts was observed both on the growth of RKO and SW48 cells and on B16F10 melanoma cells. Otherwise, an extract concentration, both cold and hot, of no less than 243 µg mL−1 is required to achieve a 50% inhibition of MCF7 cell growth.

Unveiling the therapeutic potential of thymol from Nigella sativa L. seed: selective anticancer action against human breast cancer cells (MCF-7) through down-regulation of Cyclin D1 and proliferative cell nuclear antigen (PCNA) expressions.

Breast adenocarcinoma cells (MCF-7) are characterized by the overexpression of apoptotic marker genes and proliferative cell nuclear antigen (PCNA), which promote cancer cell proliferation. Thymol, derived from Nigella sativa (NS), has been investigated for its potential anti-proliferative and anticancer properties, especially its ability to suppress Cyclin D1 and PCNA expression, which are crucial in the proliferation of cancer cells. The cytotoxicity of thymol on MCF-7 cells was assessed using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release methods. Thymol was tested at increasing concentrations (0-1000 µM) to evaluate its impact on MCF-7 cell growth. Additionally, Cyclin D1 and PCNA gene expression in thymol-treated and vehicle control groups of MCF-7 were quantified using real-time Polymerase Chain Reaction (RT-qPCR). Protein-ligand interactions were also investigated using the CB-Dock2 server. Thymol significantly inhibited MCF-7 cell growth, with a 50% inhibition observed at 200 µM. The gene expression of Cyclin D1 and PCNA was down-regulated in the thymol-treated group relative to the vehicle control. The experimental results were verified through protein-ligand interaction investigations. Thymol, extracted from NS, demonstrated specific cytotoxic effects on MCF-7 cells by suppressing the expression of Cyclin D1 and PCNA, suggesting its potential as an effective drug for MCF-7. However, additional in vivo research is required to ascertain its efficacy and safety in medical applications.

Hyaluronan-estradiol nanogels as potential drug carriers to target ER+ breast cancer cell line

An innovative hyaluronan-based nano-delivery system is proposed for the active targeting towards ER+ breast cancer. Hyaluronic acid (HA), an endogenous and bioactive anionic polysaccharide, is functionalized with estradiol (ES), a sexual hormone involved in the development of some hormone-dependent tumors, to give an amphiphilic derivative (HA-ES) able to spontaneously self-assemble in water to form soft nanoparticles or nanogels (NHs). The synthetic strategy used to obtain the polymer derivatives and the physico-chemical properties of the obtained nanogels (ES-NHs) are reported. ES-NHs ability to entrap hydrophobic molecules has also been investigated, by loading curcumin (CUR) and docetaxel (DTX), both able to inhibit the growth of ER+ breast cancer. The formulations are studied for their capability to inhibit the growth of the MCF-7 cell line, thus evaluating their efficacy and potential as a selective drug delivery systems. Our results demonstrate that ES-NHs have not toxic effects on the cell line, and that both ES-NHs/CUR and ES-NHs/DTX treatments inhibit MCF-7 cell growth, with ES-NHs/DTX effect higher than that of free DTX. Our findings support the use of ES-NHs to deliver drugs to ER+ breast cancer cells, assuming a receptor-dependent targeting.

Cytotoxic potential activity of quercetin derivatives on MCF-7 breast cancer cell line

Many previous investigations have found quercetin to be a powerful antioxidant and antitumor flavonoid, but its poor bioavailability has limited its use. This current study investigated the effects of two newly synthesized Quercetin Schiff bases containing 2-amino thiadiazole-5-thiol (Q1), and its benzyl derivatives (Q2) on MCF-7 human breast cancer cells. Cell viability and apoptosis were assessed to determine the toxic effects of Q1 and Q2. Cytotoxicity valuation showed that both compounds inhibited MCF-7 cell growth, and lactate dehydrogenase (LDH) activity increased in a dose-dependent aspect compared to the control group. Comet assay results observed that Q1 and Q2 induce more serious DNA damage than the control (untreated cell); however, in all curried experiments, Q2 showed higher effects than Q1. Hence two synthesized quercetin Schiff bases can take action as a promising anticancer agent. Keywords: quercetin derivatives, Schiff base, breast cancer, MCF-7 Cytotoxic.

Binding profile of a mixed-ligand silver(I) complex with DNA and Topoisomerase I

A new mixed-ligand Ag(I) complex, [Ag(daf)(phen)]NO3 (daf = 4,5-diazafluoren-9-one and dian = N-(4,5-diazafluoren-9-ylidene)aniline), was synthesized. The elemental analysis, FTIR, 1HNMR, UV–Vis spectroscopy, cyclic voltammetry, and DFT (Density Functional Theory) geometry optimization method were applied in order to predict the Ag(I) complex structure which concluded to a distorted tetrahedral N4 coordination around the Ag(I) center. A detailed in silico analysis of the bioaffinity of the complex to DNA and human DNA-Topoisomerase I was conducted using molecular docking simulations and ONIOM (Our own N-layered Integrated molecular Orbital and molecular Mechanics) techniques. In this overall scenario, the results suggest the dominance of π-π stacking interactions of the heteroaromatic ligands in the intercalating pocket of DNA and the active site of the enzyme and the rational correlation between being a good intercalator and a potent Topoisomerase I inhibitor. In vitro DNA-binding experiments by spectrophotometric, spectrofluorometric, Voltammetric, and viscometric techniques at physiological pH also confirmed the computational results. The complex inhibited MCF-7 cell growth in a dose-dependent manner while being nontoxic on HUVEC normal cells.

Downregulation of MDM2 by small interference RNA induces apoptosis and sensitizes MCF-7 breast cells to resveratrol.

Recent studies have demonstrated the mouse double minute gene (MDM2), a main oncogene, as a novel and interesting therapeutic target for cancer therapy. The aim of this study was to investigate the involvement of MDM2 in antiproliferative and antimetastatic effects of resveratrol in breast cancer cells. MCF-7 cells were transfected with siRNA against MDM2 and resveratrol. Proliferation and apoptosis were evaluated by MTT assay and cell death ELISA assay, respectively. MDM2, p53, Bax, Bcl-2, caspase-3, MMP-2, and MMP9 expressions were determined by qRT-PCR and Western blotting. Transfection with si-MDM2 significantly suppressed the expression of MDM2 expression, resulting in MCF-7 cell growth inhibition and spontaneous apoptosis. Pretreatment with Si-MDM2 synergically increased antiproliferation and antimetatstatic effects of resveratrol. No significant anticancer effects were detected with negative control siRNA treatment. Our findings suggest that silencing of MDM2 by specific siRNA effectively induce apoptosis and also enhanced anticancer effects of resveratrol. Therefore, siMDM2 may be a potent combination in breast therapy.

Lipopolysaccharide sensitizes the therapeutic response of breast cancer to IAP antagonist.

Inhibitor of apoptosis protein (IAP) is a class of E3 ubiquitin ligases functioning to support cancer survival and growth. Many small-molecule IAP antagonists have been developed, aiming to degrade IAP proteins to kill cancer. We have evaluated the effect of lipopolysaccharide (LPS), a component of the bacterial outer membrane, on IAP antagonists in treating breast cancer in a mouse model to guide future clinical trials. We show that LPS promotes IAP antagonist-induced regression of triple-negative breast cancer (TNBC) from MDA-MB-231 cells in immunodeficient mice. IAP antagonists such as SM-164, AT-406, and BV6, do not kill MDA-MB-231 cells alone, but allow LPS to induce cancer cell apoptosis rapidly. The apoptosis caused by LPS plus SM-164 is blocked by toll-like receptor 4 (TLR4) or MyD88 inhibitor, which inhibits LPS-induced TNFα production by the cancer cells. Consistent with this, MDA-MB-231 cell apoptosis induced by LPS plus SM-164 is also blocked by the TNF inhibitor. LPS alone does not kill MDA-MB-231 cells because it markedly increases the protein level of cIAP1/2, which is directly associated with and stabilized by MyD88, an adaptor protein of TLR4. ER+ MCF7 breast cancer cells expressing low levels of cIAP1/2 undergo apoptosis in response to SM-164 combined with TNFα but not with LPS. Furthermore, TNFα but not LPS alone inhibits MCF7 cell growth in vitro. Consistent with these, LPS combined with SM-164, but not either of them alone, causes regression of ER+ breast cancer from MCF7 cells in immunodeficient mice. In summary, LPS sensitizes the therapeutic response of both triple-negative and ER+ breast cancer to IAP antagonist therapy by inducing rapid apoptosis of the cancer cells through TLR4- and MyD88-mediated production of TNFα. We conclude that antibiotics that can reduce microbiota-derived LPS should not be used together with an IAP antagonist for cancer therapy.

Fluorizoline Blocks the Interaction between Prohibitin-2 and γ-Glutamylcyclotransferase and Induces p21Waf1/Cip1 Expression in MCF7 Breast Cancer Cells.

Prohibitin-2 (PHB2) is a scaffold protein that has pleiotropic functions, which include interacting with γ-glutamylcyclotransferase (GGCT) in the cytoplasm and repressing the transcriptional activities of the p21Waf1/Cip (p21) gene in the nucleus. The cytotoxic drug fluorizoline binds to PHB1/2 and exerts antiproliferative actions on cancer cells. However, the precise mechanism underlying the antiproliferative effects of fluorizoline is not fully elucidated. In the present study, we first show that fluorizoline induces p21 expression in several human cancer cell lines, including MCF7 breast cancer cells. Treatment of MCF7 cells with fluorizoline suppressed proliferation and prevented cells from entering into the DNA synthesis phase. Knockdown of p21 rescued the suppressed proliferation, indicating that fluorizoline inhibited MCF7 cell growth via the induction of p21. Overexpression of PHB2 in MCF7 cells prevented the induction of p21 expression by fluorizoline and restored the antiproliferative effects and blockade of cell cycle progression. Moreover, treatment of MCF7 cells with fluorizoline inhibited the interaction between endogenous PHB2 and GGCT proteins and reduced the level of nuclear localization of PHB2 proteins. These results indicate that targeting PHB2 with fluorizoline induces the expression of p21 and consequently blocks proliferation of cancer cells. SIGNIFICANCE STATEMENT: This study shows that fluorizoline may be a promising novel anticancer drug candidate that induces p21 expression and blocks cell-cycle progression in human cancer cell lines. In addition, we show that fluorizoline inhibits the interaction between PHB2 and GGCT and reduces the nuclear localization of PHB2 proteins.

Comparative binding studies of bacosine with human serum albumin and α-1-acid glycoprotein biophysical evaluation and computational approach

Bacosine (BAC) is a natural product isolated from a herb and used in the Ayurvedic system of medicine. It is reported to have a wide array of biological activities, which has generated interest in its therapeutic potential. To better understand how BAC may operate as a potential anti-cancer therapeutic, we examined its anti-cancer properties in the human breast cancer cell line, MCF-7. In order to get an idea of how it may behave in vivo, we also evaluated its interaction with human serum albumin (HSA) and α-1-acid glycoprotein (AGP) using fluorescence spectroscopy and in silico molecular modelling. Based on our in vitro studies, we found that BAC inhibited MCF-7 cell growth in a dose-dependent manner with an IC50 value of 9 µM. In addition, the intrinsic fluorescence of HSA and AGP was quenched by BAC, consistent with a static quenching mechanism. Fluorescence emission spectroscopy revealed a binding of 2.97 ± 0.01 × 104 M−1 for HSA-BAC which corresponded to a free energy change of − 6.07 kcal/mol at 25 °C. In addition, we found that BAC had a binding constant of 1.8 ± 0.02 × 103 M−1 to AGP which corresponded to a change in free energy − 4.42 kcal/mol at 25 °C. We also identified the site of BAC binding to the HSA protein using the site-specific marker, phenylbutazone, along with molecular docking studies. Circular dichroism spectra revealed partial changes in the secondary structure of HSA in the presence of BAC suggesting direct interactions. Molecular dynamics simulations demonstrated that the HSA-BAC complex reaches an equilibration state at around 4 ns, suggesting that the HSA-BAC complex is quite stable. Our results provide evidence that serum proteins can act as a carrier protein for BAC, potentially impacting its development as an anti-cancer agent.

Synergistic anti-cancer effects of silibinin-etoposide combination against human breast carcinoma MCF-7 and MDA-MB-231 cell lines.

Objective(s):Recently, there is a significant focus on combination chemotherapy for cancer using a cytotoxic drug and a phytochemical compound. We investigated the effect of silibinin on etoposide-induced apoptosis in MCF-7 and MDA-MB-231 breast carcinoma cell lines.Materials and Methods:The cytotoxic effects of silibinin and etoposide were determined using MTT assay after 24 and 48 hr incubation with these drugs individually and combined. The mRNA expression of Bax and Bcl2, and protein levels of P53, phosphorylated p53 (P-P53), and P21 were determined using real-time PCR and western blot analysis, respectively. The caspase 9 activity was measured using an ELISA kit. Results:Silibinin and etoposide alone and combined significantly inhibit cell growth in a dose and time-dependent manner in both cell lines. The strongest synergistic effects in terms of MCF-7 cell growth inhibition [combination index (CI) = 0.066] were evident. The silibinin-etoposide combinations cause a much powerful apoptotic death (47% and 40%) compared with each compound individually in MCF-7 and MDA-MB 231 cells, respectively. Additionally, the silibinin-etoposide combinations significantly increased the expression of P53, P-P53, and P21 in MCF-7 cells. Neither silibinin nor etoposide individually increased the level of P53 and P-P53 in MDA-MB-231 cells, but both of them individually and combined increased the level of P21.Conclusion:Since the silibinin-etoposide combination induces apoptosis in both cell lines with and without expression of p53, thus, it is suggested that this combination may be a successful therapeutic strategy for breast cancer regardless of P53 status.

Abstract 990: Differential immunoregulatory effects of decitabine on lipid metabolism in doxurobicin versus tamoxifen treated breast cancer cells

Abstract Background: The treatment of hormonal positive breast cancer is still based on hormonal tamoxifen (TAM) based regimens in early stages, while based on chemotherapeutic doxorubicin (DOX) based regimens in late stages. DNA methyl transferase inhibitor (decitabine: DEC) is an epigenetic modulator with synergistic anticancer activity when combined with either TAM or DOX. Aims: The cytotoxic synergistic combinations of DEC with either DOX or TAM were examined for their effects on immunomodulation and lipid metabolism in hormonal positive breast cancer cells (MCF7). Material and Methods: Sulphorhodamine-B cytotoxic assay, flow cytometric analysis of cell cycle and apoptosis along with the florescent uptake of Rhodamine123 were adopted for testing the sensitivity of MCF7 cells to the drug combinations. Real time PCR was utilized to measure the genetic expression of immunoregulatory markers (FOXP3, TNFα, IFNγ and IL-6), lipid metabolism regulatory markers (FASN, CPT1, MLYCD, ACCα and AMPK) and apoptosis markers (BAX, BCL2, Caspase-8, AKT, mTOR). Western Blotting was used for the determination of EGFR, CK7, LC3B proteins expressions. Results: The combination with 500nM DEC caused synergistic 50% growth inhibition of MCF7 cells, in which the concentration required for DOX was reduced from 0.501 µM into 0.264µM, while in TAM, the concentration was reduced from 18µM into 12.4µM. The concentration of 500nM DEC induced the uptake of Rhodamine 123 and the expression of Caspase-8, IFNγ, IL-6 and AMPK in the combination with 20µM TAM or 0.25µM DOX compared with their respective single treatment concentrations. Also, both DEC combinations reduced the expressions of BAX/BCl2, EGFR, CK7, aromatase, LC3B and ACCα, but caused insignificant effect on FASN expression. The combination of 500nM DEC with 20µM TAM demonstrated significant accumulation of cells in the G0/G1 phase of the cell cycle (4.22%), and in the early apoptosis (8.97%), along with the increase of mTOR but decrease of CPT1A, MLYCD, TNFα genes expressions. On the other hand, the combination of 500nM DEC with 0.25µM DOX caused accumulation of 94.73% of cells in the late apoptosis, inhibition of the AKT and FOXP3 expressions, but induction of CPT1A. Conclusions: Epigenetic modifier (DEC) showed different synergistic immunomodulatory effects on lipid metabolism regulation markers when combined with chemotherapy (DOX) rather than hormonal therapy (TAM) in hormonal positive breast cancer cells. DEC induces extrinsic late apoptosis through the induction of CPT1A- mediated lipid metabolism along with FOXP3 and AKT inhibition in DOX treated cells, while it induces extrinsic early apoptosis through the inhibition of MLYCD, CPT1A and TNFα in TAM treated cells. Citation Format: Mariam Fouad, Mohammed Sayed-Ahmed. Differential immunoregulatory effects of decitabine on lipid metabolism in doxurobicin versus tamoxifen treated breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 990.

Evaluation of antioxidant property and anticancer prospective of the leaf extract and biofractions of Bauhinia foveolata Dalzell – A native of the Indian Western Ghats

The current study was designed to evaluate the antioxidant and anticancer potential of ethanolic leaf extract of Bauhinia foveolata Dalzell. (EEBF) and its toluene, ethyl acetate and methanolic biofractions viz., TFBF, EFBF and MFBF. Phytoconstituents were screened by adopting established procedures. Total phenolic and flavonoid content were assessed spectrophotometrically. In vitro antioxidant activity was assayed using DPPH (2,2-diphenyl-1-picrylhydrazyl), hydrogen peroxide and nitric oxide as free radicals, whereas anticancer activity was evaluated using sulforhodamine B assay. EEBF showed maximum phenolic content of 49.12±0.31 mg GAE/g and flavonoidal content of 28.75±0.42 mg QUE/g, than its biofractions. EEBF showed considerable antioxidant activity with IC50=19.04±0.24 μg/mL and IC50=65.85±1.22 μg/mL when compared to the standards Ascorbic acid (IC50=12.06±0.05 μg/mL) and Gallic acid (IC50=64.65±0.72 μg/mL) in DPPH and nitric oxide scavenging assays, respectively. MFBF showed significant activity with IC50=26.76±0.75 μg/mL in hydrogen peroxide scavenging assay compared to the standard Gallic acid (IC50=76.60±1.31 μg/mL). TFBF showed favourable growth inhibition of MCF-7 cells with GI50=73.5±11.96 µg/mL when compared to other samples screened (GI50>80 μg/mL) as against the standard Adriamycin (GI50<10 μg/mL) in SRB assay. The therapeutic virtues of EEBF and MFBF as free radical scavengers and TFBF as an antiproliferative may be attributed to the phenolics, flavonoids, steroids and triterpenoids present.

Incorporation of Sulfonamide Moiety into Biguanide Scaffold Results in Apoptosis Induction and Cell Cycle Arrest in MCF-7 Breast Cancer Cells.

Metformin, apart from its glucose-lowering properties, has also been found to demonstrate anti-cancer properties. Anti-cancer efficacy of metformin depends on its uptake in cancer cells, which is mediated by plasma membrane monoamine transporters (PMAT) and organic cation transporters (OCTs). This study presents an analysis of transporter mediated cellular uptake of ten sulfonamide-based derivatives of metformin in two breast cancer cell lines (MCF-7 and MDA-MB-231). Effects of these compounds on cancer cell growth inhibition were also determined. All examined sulfonamide-based analogues of metformin were characterized by greater cellular uptake in both MCF-7 and MDA-MB-231 cells, and stronger cytotoxic properties than those of metformin. Effective intracellular transport of the examined compounds in MCF-7 cells was accompanied by high cytotoxic activity. For instance, compound 2 with meta-methyl group in the benzene ring inhibited MCF-7 growth at micromolar range (IC50 = 87.7 ± 1.18 µmol/L). Further studies showed that cytotoxicity of sulfonamide-based derivatives of metformin partially results from their ability to induce apoptosis in MCF-7 and MDA-MB-231 cells and arrest cell cycle in the G0/G1 phase. In addition, these compounds were found to inhibit cellular migration in wound healing assay. Importantly, the tested biguanides are more effective in MCF-7 cells at relatively lower concentrations than in MDA-MB-231 cells, which proves that the effectiveness of transporter-mediated accumulation in MCF-7 cells is related to biological effects, including MCF-7 cell growth inhibition, apoptosis induction and cell cycle arrest. In summary, this study supports the hypothesis that effective transporter-mediated cellular uptake of a chemical molecule determines its cytotoxic properties. These results warrant a further investigation of biguanides as putative anti-cancer agents.

The Antioxidant Carrichtera annua DC. Ethanolic Extract Counteracts Cisplatin Triggered Hepatic and Renal Toxicities.

Cisplatin is a powerful anti-neoplastic drug that displays multi-organ toxicity, especially to the liver and kidneys. Consumption of phytomedicines is a promising strategy to overcome the side effects of chemotherapy. Carrichtera annua extract proved to possess potent antioxidant activity. Its protective potential against cisplatin-induced hepato–nephrotoxicity was scrutinized. Moreover, a phytochemical study was conducted on C. annua ethyl acetate fraction which led to the isolation of five known phenolic compounds. Structure determination was achieved utilizing 1H- and 13C-NMR spectral analyses. The isolated phytochemicals were trans-ferulic acid (1), kaempferol (2), p-coumaric acid (3), luteolin (4) and quercetin (5). Regarding our biological study, C. annua has improved liver and kidney deteriorated functions caused by cisplatin administration and attenuated the histopathological injury in their tissues. Serum levels of ALT, AST, blood urea nitrogen and creatinine were significantly decreased. C. annua has modulated the oxidative stress mediated by cisplatin as it lowered MDA levels while enhanced reduced-GSH concentrations. More importantly, the plant has alleviated cisplatin triggered inflammation, apoptosis via reduction of INFγ, IL-1β and caspase-3 production. Moreover, mitochondrial injury has been ameliorated as remarkable increase of mtDNA was noted. Furthermore, the MTT assay proved the combination of cisplatin—C. annua extract led to growth inhibition of MCF-7 cells in a notable additive way. Additionally, we have investigated the binding affinity of C. annua constituents with caspase-3 and IFN-γ proteins using molecular simulation. All the isolated compounds exhibited good binding affinities toward the target proteins where quercetin possessed the most auspicious caspase-3 and IFN-γ inhibition activities. Our results put forward that C. annua is a promising candidate to counteract chemotherapy side effects and the observed activity could be attributed to the synergism between its phytochemicals.

In vitro and invivo Study of Banana Peel Extract Anti Toxicity

In this study, extraction of the banana peels were done by two solvent kinds and water. Cytotoxic activityof the extracts were tested by using assay of MTT. Inhibition of cells was 68.2% when banana peel wasextracted by hexane, and the effect of its cytotoxicity was the highest at 100 ?g/ml. On the other hand,growth inhibition of MCF-7 cells was recorded at this concentration. While, ethanol extract was at thesecond stage according to its cytotoxicity which reached 54.1% followed by watery extract which showed46.9%.Antimicrobial activity of banana peel extractswas tested against some pathogenic bacteria andshowed the capacity to have abroad range of inhibition activities against isolates E. coli, klebsiellaspp, S.aureus, P. aeruginosa, extracts demonstrated inhibition zones which were greater than 20,10,15 mm againstE. coli,klebsiella andstaph. spp. respectively, but did not affect P. aeroginosa Also, experimental animalswere exposured to these extracts. It was revealed that NTEC (CNF2) toxin made few chronic inflammatorycells proliferation, hyperplasia of lymphoid tissue and some cases of atrophy in the villi. Current resultsshowed low impact on tissue cells when banana peel extracts were used.

Synthesis of erythro- B13 enantiomers and stereospecific action of full set of B13-isomers in MCF7 breast carcinoma cells: Cellular metabolism and effects on sphingolipids

B13 is an acid ceramidase (ACDase) inhibitor. The two chiral centers of this aromatic amido alcohol lead to four stereoisomers, yet we have little knowledge about its erythro- enantiomers, (1R, 2S) and (1S, 2R). In this paper, for the first time, the synthesis of two erythro- enantiomers is described, and the compounds are evaluated along with two threo- enantiomers, (1R, 2R) and (1S, 2S). The key metabolites and sphingolipid (SL) profile of the full set of B13 stereoisomers in MCF7 breast carcinoma cells are presented. The results demonstrated that the erythro- enantiomers were more effective than the threo- enantiomers on growth inhibition in MCF7 cells, although there were no statistically significant differences within the threo- and erythro- series. Measurement of intracellular levels of the compounds indicated that the erythro- seemed a little more cell permeable than the threo- enantiomers; also, the (1R, 2S) isomer with the same stereo structure as natural ceramide (Cer) could be hydrolyzed and phosphorylated in MCF7 cells. Furthermore, we also observed the formation of C16 homologs from the full set of B13 isomers within the cells, indicating the occurrence of de-acylation and re-acylation of the amino group of the aromatic alcohol. Moreover, the decrease in the Cer/Sph ratio suggests that the growth inhibition from (1R, 2S) isomer is not because of the inhibition of ceramidases. Taken together, (1R, 2S) could be developed as a substitute of natural Cer.

Cancer Cell Membrane Camouflaged Semi-Yolk@Spiky-Shell Nanomotor for Enhanced Cell Adhesion and Synergistic Therapy.

Cell adhesion of nanosystems is significant for efficient cellular uptake and drug delivery in cancer therapy. Herein, a near-infrared (NIR) light-driven biomimetic nanomotor is reported to achieve the improved cell adhesion and cellular uptake for synergistic photothermal and chemotherapy of breast cancer. The nanomotor is composed of carbon@silica (C@SiO2 ) with semi-yolk@spiky-shell structure, loaded with the anticancer drug doxorubicin (DOX) and camouflaged with MCF-7 breast cancer cell membrane (i.e.,mC@SiO2 @DOX). Such biomimetic mC@SiO2 @DOX nanomotors display efficient self-thermophoretic propulsion due to a thermal gradient generated by asymmetrically spatial distribution. Moreover, the MCF-7 cancer cell membrane coating can remarkably reduce the bioadhesion of nanomotors in biological medium and exhibit highly specific self-recognition of the source cell line. The combination of effective propulsion and homologous targeting dramatically improves cell adhesion and the resultant cellular uptake efficiency in vitro from 26.2% to 67.5%. Therefore, the biomimetic mC@SiO2 @DOX displays excellent synergistic photothermal and chemotherapy with over 91% MCF-7 cell growth inhibition rate. Such smart design of the fuel-free, NIR light-powered biomimetic nanomotor may pave the way for the application of self-propelled nanomotors in biomedicine.

GSF3, a polysaccharide from guava (Psidium guajava L.) seeds, inhibits MCF-7 breast cancer cell growth via increasing Bax/Bcl-2 ratio or Fas mRNA expression levels

Guava seed polysaccharide fraction 3 (GSF3) is an immunomodulatory polysaccharide from guava (Psidium guajava L.) seed polysaccharides. However, effects of GSF3 on the growth of breast cancer cells were not understood, yet. To clarify the GSF3 effects on breast cancer cell growth, GSF3 was subjected to treat MCF-7 cells using direct action or indirect immunotherapy using immune cells conditioned media, respectively. The viabilities of MCF-7 cells were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Changes in pro-(Bax)/anti-apoptotic (Bcl-2) and Fas mRNA expression levels in the treated MCF-7 cells were measured using two-step reverse transcription quantitative polymerase chain reaction. Our results showed that GSF3 inhibited MCF-7 cell growth through either direct action or indirect immunotherapy. GSF3 direct action significantly (P < 0.05) decreased Bcl-2 mRNA expression amount but increased pro-(Bax)/anti-apoptotic (Bcl-2) mRNA expression ratios in the treated cells. The splenocytes conditioned media cultured with GSF3 increased Fas mRNA expression amounts in the treated MCF-7 cells. There was a significant negative correlation between Th2-polarized cytokines secreted by immune cells and Fas mRNA expression levels in the corresponding treated MCF-7 cells. Our findings suggested that GSF3 is a potent anti-cancerous polysaccharide by direct action or indirectly modulating immune cell cytokine secretion profiles.

The Analysis of the Anti-Tumor Mechanism of Ursolic Acid Using Connectively Map Approach in Breast Cancer Cells Line MCF-7.

BackgroundUrsolic acid (UA), a primary bioactive triterpenoid, was reported as an anti-cancer agent. However, the current knowledge of UA and its potential anti-cancer mechanisms and targets in breast cancer cells are limited. In this study, we aimed to illustrate the potential mechanisms and targets of UA in breast cancer cells MCF-7.MethodsThe effect of UA on cell growth was determined in MCF-7 cells by MTT assay. The anti-tumor mechanism of UA was evaluated by microarray, CAMP, and Western blot. Moreover, the molecular docking between UA and potential receptors were predicted by iGEMDOCK software.ResultsThe result of MTT assay demonstrated that UA could inhibit MCF-7 cell growth with IC50 values of 20 μM. Microarray and CMAP analysis, validated by Western blot, indicated that UA significantly modulated IKK/NF-κB, RAF/ERK pathways, and down-regulated the phosphorylation level of PLK1 in MCF-7 cells.ConclusionOur data indicated that the anti-tumor effects of UA are due to the inhibited RAF/ERK pathway and IKK/NF-κB pathway. It could also be explained by the reduced phosphorylation of PLK1 in MCF-7 cells. This study provides a new insight for deep understanding of the new anti-cancer mechanisms of UA in MCF-7 breast cancer cells.

M1 Polarization but Anti-LPS-Induced Inflammation and Anti-MCF-7 Breast Cancer Cell Growth Effects of Five Selected Polysaccharides.

Five potential polysaccharides from guava seed (GSPS), common buckwheat (CBPS), bitter buckwheat (BBPS), red Formosa lambsquarters (RFLPS), and yellow Formosa lambsquarters (YFLPS) were selected to measure their effects on mouse peritoneal macrophages in the absence or presence of lipopolysaccharide (LPS). Macrophage-conditioned media (MCM) in the absence or presence of 5 selected polysaccharides were prepared to treat MCF-7 cells. The cell viability was determined using 3-(4,5-dimethylthiazol-2-diphenyl)-2,5-tetrazolium bromide (MTT) assay. Proinflammatory (also known as M1 type) (interleukin- (IL-) 1β, IL-6 and tumor necrosis factor- (TNF-) α) and anti-inflammatory (also known as M2 type) (IL-10) cytokines secreted by macrophages were determined using ELISA. The relationship between MCF-7 cell growth and M1/M2 cytokine secretion profiles in the corresponding MCM were delineated. The results showed that 5 selected polysaccharides, except BBPS, significantly (P < 0.05) and dose-dependently increased M1 (IL-1β + IL-6 + TNF-α)/M2 (IL-10) cytokine secretion ratios by macrophages in the absence of LPS, suggesting that four selected polysaccharides have M1 polarization property. However, all of 5 selected polysaccharides significantly (P < 0.05) decreased proinflammatory (IL-1β + IL-6 + TNF-α)/anti-inflammatory (IL-10) cytokine secretion ratios by LPS-stimulated macrophages, exhibiting that all of the 5 selected polysaccharides, particularly GSPS, have anti-inflammatory potential. All MCM prepared with these selected polysaccharides (except YFLPS) significantly enhanced their inhibitory effects on MCF-7 cell growth. A negative correlation was noted between MCF-7 cell viabilities and M1/M2 cytokine secretion ratios ((IL-6 + TNF-α)/IL-10) in the corresponding MCM, suggesting that increases in M1 macrophages in the tumor microenvironment might inhibit MCF-7 cell growth. Particular polysaccharides including RFLPS, GSPS, YFLPS, and CBPS may increase the percentage of M1 macrophages in the tumor environment and further inhibit MCF-7 cell growth via immunotherapy.