Human Breast MCF-7 Cells Research Articles

Synthesis, characterisation and in vitro anticancer activity of conjugated protease inhibitor-silver nanoparticles (AgNPs-PI) against human breast MCF-7 and prostate PC-3 cancer cell lines.

The conjugated silver nanoparticles using biomolecules have attracted great attention of researchers because physical dimensions and surface chemistry play important roles in toxicity and biocompatibility of AgNPs. Hence, in the current study, synthesis of bio-conjugated AgNPs with protein protease inhibitor (PI) isolated from Streptomyces spp. is reported. UV-visible spectra of PI and AgNPs showed stronger peaks at 280 and 405nm, confirming the synthesis of conjugated AgNPs-PI. TEM and SEM images of AgNPs-PI showed spherical-shaped nanoparticles with a slight increase in particle size and thin amorphous layer around the surface of silver nanomaterial. Circular dichroism, FT-IR and fluorescence spectral studies confirmed AgNPs-PI conjugation. Conjugated AgNPs-PI showed excellent anticancer potential than AgNPs and protease inhibitor separately on human breast MCF-7 and prostate PC-3 cell lines. The findings revealed that surface modification of AgNPs with protein protease inhibitor stabilised the nanomaterial and increased its anticancer activity.

Identification of Bioactive Components and in vitro Cytotoxicity Analysis of Annona squamosa Extract on Human Breast Cancer Cells

The present study is to explore to determine the bioactive components and in vitro cytotoxicity of the chloroform extract of Annona squamosa analyzed. Materials and Methods: The aerial parts of chloroform extract of the medicinal plant Annona squamosa were used to regulate the bioactive components and their in vitro analysis of cytotoxicity was ceased by vero and human breast MCF-7 cell lines were analyzed by gas chromatography and mass spectrometry and MTT assay respectively. Results: The present study envisages 12 phytocompounds and their significant cytotoxic role on Vero as well as human breast carcinoma and MCF-7 cell lines. Conclusion: Herbal medicinal plants have been extensively studied for their possible medicinal value as primary source drugs. Obviously, the natural products from the herbal medicinal sources will continue to be extremely important as sources of medicinal agents.

Furo[2,3-d]pyrimidines as Mackinazolinone/Isaindigotone Analogs: Synthesis, Modification, Antitumor Activity, and Molecular Docking Study.

The chemical transformation of the tricyclic furo[2,3-d]pyrimidines was performed under isosteric and scaffold-hopping strategies focusing on the synthesis of its arylidene and imine-containing derivatives. Naturally-occurring alkaloids mackinazolinone and isaindigotone were as templates of target heterocycles. Synthesized compounds evaluated for their antitumor activity on human cancer cervical HeLa, breast MCF-7, and colon HT-29 cell lines. Four compounds: 8c, 8e, 10b, and 10c demonstrated potency against HeLa and HT-29 cell lines, and IC50 values were between 7.37-13.72 μM, respectively. The molecular docking results showed that compounds 8c and 10b had good binding and high matching with the target EGFR protein.

Capsaicin-loaded alginate nanoparticles embedded polycaprolactone-chitosan nanofibers as a controlled drug delivery nanoplatform for anticancer activity

Nanocarrier-based drug delivery systems have been designed into various structures that can effectively prevent cancer progression and improve the therapeutic cancer index. However, most of these delivery systems are designed to be simple nanostructures with several limitations, including low stability and burst drug release features. A nano-in-nano delivery technique is explored to address the aforementioned concerns. Accordingly, this study investigated the release behavior of a novel nanoparticles-in-nanofibers delivery system composed of capsaicin-loaded alginate nanoparticles embedded in polycaprolactone-chitosan nanofiber mats. First, alginate nanoparticles were prepared with different concentrations of cationic gemini surfactant and using nanoemulsion templates. The optimized formulation of alginate nanoparticles was utilized for loading capsaicin and exhibited a diameter of 19.42 ± 1.8 nm and encapsulation efficiency of 98.7 % ± 0.6 %. Likewise, blend polycaprolactone-chitosan nanofibers were prepared with different blend ratios of their solutions (i.e., 100:0, 80:20, 60:40) by electrospinning method. After the characterization of electrospun mats, the optimal nanofibers were employed for embedding capsaicin-loaded alginate nanoparticles. Our findings revealed that embedding capsaicin-loaded alginate nanoparticles in polycaprolactone-chitosan nanofibers, prolonged capsaicin release from 120 h to more than 500 h. Furthermore, the results of in vitro analysis demonstrated that the designed nanoplatform could effectively inhibit the proliferation of MCF-7 human breast cells while being nontoxic to human dermal fibroblasts (HDF). Collectively, the prepared nanocomposite drug delivery platform might be promising for the long-term and controlled release of capsaicin for the prevention and treatment of cancer.

Chemical characterization and antineoplastic effect of oligosaccharides from Cabernet Franc red wine in mammary tumor model in mice

The present study characterized oligosaccharide compounds (Oligo) in Cabernet Franc red wine and investigated its antineoplastic effects against mammary tumor cells in vivo and in vitro, isolated or in combination with chemotherapy. The Oligo fraction was characterized by nuclear magnetic resonance spectroscopy and mass spectrometry. The complex mixture of Oligo showed high amounts of oligoxyloglucuronans, oligorhamnogalacturonans, oligoarabinogalactans, and oligoglucans, such as trehalose and isomaltotriose. To investigate the antineoplastic effects of Oligo, Female Swiss mice were subcutaneously inoculated with Ehrlich tumor cells and then received vehicle (distilled water, p.o.), Oligo solution (9, 35, or 70 mg/kg, p.o.), or methotrexate (1.5 mg/kg, i.p.). The treatments were administered in a conventional (21-d) or chemopreventive (42-d) protocol. Oligo reduced the growth of Ehrlich tumors in both protocols and increased the effectiveness of methotrexate in controlling tumor growth. Oligo did not reduce the viability of MCF-7, MDA-MB-231, MDA-MB-436, and HB4a human breast cells that were cultured for 48 h, showing no cytotoxicity. Overall, Oligo exerted an in vivo antineoplastic effect and modulated immune blood cells, dependent on treatment time, and was not directly cytotoxic to tumor cells. Thus, Oligo may indirectly regulate tumor cell development and may be a promising drug for cancer therapy in combination with methotrexate.

Bio-Based Electrospun Fibers from Chitosan Schiff Base and Polylactide and Their Cu2+ and Fe3+ Complexes: Preparation and Antibacterial and Anticancer Activities.

The Schiff base derivative (Ch-8Q) of chitosan (Ch) and 8-hydroxyquinoline-2-carboxaldehyde (8QCHO) was prepared and fibrous mats were obtained by the electrospinning of Ch-8Q/polylactide (PLA) blend solutions in trifluoroacetic acid (TFA). Complexes of the mats were prepared by immersing them in a solution of CuCl2 or FeCl3. Electron paramagnetic resonance (EPR) analysis was performed to examine the complexation of Cu2+(Fe3+) in the Ch-8Q/PLA mats complexes. The morphology of the novel materials and their surface chemical composition were studied by scanning electron microscopy (SEM), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS). The performed microbiological screening demonstrated that in contrast to the neat PLA mats, the Ch-8Q-containing mats and their complexes were able to kill all S. aureus bacteria within 3 h of contact. These fibrous materials had efficiency in suppressing the adhesion of pathogenic bacteria S. aureus. In addition, Ch-8Q/PLA mats and their complexes exerted good anticancer efficacy in vitro against human cervical HeLa cells and human breast MCF-7 cells. The Ch-8Q-containing fibrous materials had no cytotoxicity against non-cancer BALB/c 3T3 mouse fibroblast cells. These properties render the prepared materials promising as wound dressings as well as for application in local cancer treatment.

Size-resolved counting of circulating tumor cells on pinched flow-based microfluidic cytometry.

Precise cell detecting and counting is meaningful in circulating tumor cells (CTCs) analysis. In this work, a simple cyclic olefin copolymer (COC) microflow cytometer device was developed for size-resolved CTCs counting. The proposed device is constructed by a counting channel and a pinched injection unit having three channels. Through injection flow rate control, microspheres/cells can be focused into the centerline of the counting channel. Polystyrene microspheres of 3, 9, 15, and 20µm were used for the microspheres focusing characterization. After coupling to laser-induced fluorescence detection technique, the proposed device was used for polystyrene microspheres counting and sizing. A count accuracy up to 97.6% was obtained for microspheres. Moreover, the proposed microflow cytometer was applied to CTCs detecting and counting. To mimic blood sample containing CTCs and CTCs mixture with different subtypes, an MDA-MB-231 (human breast cell line) spiked red blood cells sample and a mixture of MDA-MB-231 and MCF-7 (human breast cell line) sample were prepared, respectively, and then analyzed by the developed pinched flow-based microfluidic cytometry. The simple fabricated and easy operating COC microflow cytometer exhibits the potential in the point-of-care clinical application.

Cytotoxicity and Toxicological Studies of Artocarpus altilis Extracts, Inducing Apoptosis and Cell Cycle Arrest via CASPASE-3 and CASPASE-8 Pathways against Human Breast MCF-7 Cells.

In recent biomedical research, the area of cancer and infectious diseases occupies a leading position in the utilization of medicinal plants as a source of drug discovery. Malaysia has a diversity and a large number of underutilized fruits that are rich in phenolic compounds. Artoarpus altilis is considered an underutilized fruit that is rich in phenolic compounds. Methanol extracts of A. altilis have been previously found to contain a high content of antioxidant phytochemicals. The purpose of the study was to evaluate the cytotoxicity and toxicological effect of methanol fruit extracts against MCF-7 cells. To determine the least concentration that might kill or suppress the growth of the cancer cells was in a concentration-dependent manner. The variation in the cytotoxic activity among the extracts was indicated by determining the IC50 of each extract against cells at 72 h. The IC50 of the samples was measured using a trypan blue exclusion assay. The methanol extract of the pulp part showed the least inhibition concentration of 15.40±0.91 μg/mL on MCF-7 cells. In the study, the molecular mechanism of methanol extracts-induced apoptosis and cell cycle arrested in human cancer cells were investigated in a time-dependent-manner by using flow cytometry. The treated cells were stained with nexin to detect early and late apoptosis and with propidium iodide (PI) for cell cycle arreste associated with the DNA fragmentation; various cell arrests occurred at G1/S, S, and G2/M phases. Lastly, the gene expression analysis by RT-qPCR method was carried out by analyzing the expression of the gene of interest for the quantification of mRNA levels. Results after cells were treated with IC50 were revealed by upregulating anti-apoptotic genes/downregulated of pro-apoptotic BCL-2 gene expressions triggered the treated cells into CASPASE- 3, intrinsic and extrinsic pathways. These findings suggest that the methanol extracts of three parts of A. altilis fruit have potential anticancer activity against MCF-7 cells mainly the pulp part of the fruit.

Comparison of the Toxicological Effects of Pesticides in Non-Tumorigenic MCF-12A and Tumorigenic MCF-7 Human Breast Cells.

Humans are exposed to residues of organophosphate and neonicotinoid pesticides, commonly used in agriculture. Children are particularly vulnerable and, among possible adverse outcomes, the increased incidence of premature mammary gland development (thelarche) has raised concern. We evaluated the toxicological effects of chlorpyrifos (CPF), imidacloprid (IMI) and glyphosate (GLY) at exposure concentrations occurring in children on the tumorigenic MCF-7 and non-tumorigenic MCF-12A breast cell lines, as representative of the target organ model, assessing cytotoxicity, apoptosis, necrosis, intracellular reactive oxygen species (ROS) and ATP levels, 17β-estradiol secretion and gene expression of nuclear receptors involved in mammary gland development. The pesticides decreased cell vitality in MCF-7 and cell proliferation in MCF-12A cells. ATP levels were decreased in MCF-7 cells by pesticides and apoptosis was increased in MCF-12A cells only by GLY (2.3 nM). ROS production was decreased by pesticides in both cell lines, except IMI (1.6 nM) in MCF-7 cells. Endocrine disrupting activity was highlighted by induction of 17β-estradiol secretion and modulation of the gene expression of estrogen alpha and beta, progesterone, androgen, and aryl hydrocarbon receptors in both cell lines. The use of MCF-7 and MCF-12A cells highlighted dissimilar modes of action of each pesticide at low human relevant concentrations.

GC-MS profiling, antioxidant, antimicrobial activities, DNA cleavage effect of Symphytum aintabicum Hub.-Mor. & Wickens (Boraginaceae) and its anticancer activity on MCF-7 cell line

Symphytum species, generally known as comfrey, have been used for ancient times in folk medicine for wounds, bone breakages, rheumatism, liver problems, and innumerable potentialities. However, many of the species belonging to the genus Symphytum have not been analyzed with scientific methods and principles yet. Therefore, this work is a guide for determining and researching the main gaps in the literature. In this study, MeOH and petroleum ether (PE) extracts of Symphytum aintabicum Hub.-Mor. & Wickens were analyzed for their biological activities and GC-MS analysis, antioxidant, antimicrobial activities, DNA cleavage effect, and anticancer activity on the MCF-7 human breast cell line. The phytochemical constituents of the main composition of S. aintabicum extracts were determined. The MeOH extract was found to contain higher concentrations of phenolic 90.87 (±5.30) mg (GAE)/g extract and flavonoid 98.00 (± 9.72) mg (CE)/g extract substances in comparison to the PE extract. The extracts displayed significant ABTS activity and it was found that the IC50 values of the PE and MeOH extracts were calculated as 6.88 mg/mL (±0.11) and 0.032 mg/mL ±0.002), respectively. According to the data obtained, PE extract demonstrated more antimicrobial activity than the MeOH extracts. The PE and MeOH extracts was found to have strongest antimicrobial activity on Micrococcus luteus, E. coli (125 ?g/mL; 250 ?g/mL) and Candida albicans (1000 ?g/mL), respectively. Additionally, the effects of plant extracts on DNA cleavage were investigated using pBR322 plasmid DNA, and it was found that the PE extract was more effective than the MeOH extract in both the presence and absence of H2 O2 . In the MTT assay, the lowest % cell viability values in the PE and MeOH extracts were 42.79% and 47.77% at 500 ppm, respectively. The IC50 values for the PE and MeOH extracts were 414.73 ?g/mL and 443.31 ?g/mL. Findings of this study show that S. aintabicum has shown interesting pharmacological and biological activities, and is a particularly suitable candidate for anticancer drug development.

Attenuation of Tumor Development in Mammary Carcinoma Rats by Theacrine, an Antagonist of Adenosine 2A Receptor.

Caffeine has been reported to induce anti-tumor immunity for attenuating breast cancer by blocking the adenosine 2A receptor. Molecular modeling showed that theacrine, a purine alkaloid structurally similar to caffeine, might be an antagonist of the adenosine 2A receptor equivalent to or more effective than caffeine. Theacrine was further demonstrated to be an effective antagonist of the adenosine 2A receptor as its concurrent supplementation significantly reduced the elevation of AMPK phosphorylation level in MCF-7 human breast cells induced by CGS21680, an agonist of adenosine 2A receptors. In an animal model, the development of mammary carcinoma induced by 7,12-Dimethylbenz[a]anthracene in Sprague–Dawley rats could be attenuated by daily supplement of theacrine of 50 or 100 mg/kg body weight. Both expression levels of cleaved-caspase-3/pro-caspase-3 and granzyme B in tumor tissues were significantly elevated when theacrine was supplemented, indicating the induction of programmed cell death in tumor cells might be involved in the attenuation of mammary carcinoma. Similar to the caffeine, significant elevation of interferon-γ and tumor necrosis factor-α was observed in the serum and tumor tissues of rats after the theacrine supplement of 50 mg/kg body weight. Taken together, theacrine is an effective antagonist of adenosine 2A receptors and possesses great potential to be used to attenuate breast cancer.

Synthesis of core-shell structure based on silica nanoparticles and methacrylic acid via RAFT method: An efficient pH-sensitive hydrogel for prolonging doxorubicin release

In recent years, much attention has been received on stimuli-responsive nanocarriers in nanomedicine. In this work, a pH-responsive core-shell system based on silica nanoparticles (SNPs) as core and methacrylic acid hydrogels as shell were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Methacrylic acid hydrogel through bulk and RAFT polymerization was developed as a model to compare with core-shell hydrogel. The synthesized nanocarriers were characterized by TGA, FT-IR, SEM, TEM, and DLS techniques. To investigate the synthesized core-shell nanoparticles as anticancer nanocarriers, Doxorubicin (DOX) was used as a model drug. In-vitro drug release manner at physiological barriers (pH 7.4) and cancer cell conditions (pH 4.8) illustrates a pH-controlled release for the nanocarriers over 15 days. The study of drug release kinetics reveals that the release mechanism of the carriers followed by the Gompertz model. In addition, the DOX-loaded nanocarriers have notable cytotoxicity against human breast MCF-7 cells with 0.7866 μM IC50 for core-shell nanocarrier. The obtained results showed that the prepared pH-responsive core-shell hydrogel has a high potential to be employed as a sustained pH-sensitive drug release system.

Design, synthesis, biological evaluation and molecular modeling investigation of new N'-(2-Thiouracil-5-oyl) hydrazone derivatives as potential anti-breast cancer and anti-bacterial agents

A series of novel N’-(2-thiouracil-5-oyl)hydrazones were designed and chemically synthesized using an active substructure combination method. The synthesized compounds were structurally characterized on the basis of elemental (%) analyses, IR, MS, 1H NMR, and 13C NMR spectra. All the prepared compounds were evaluated in vitro against MCF-7 human breast cell line using MTT assay. The anticancer results showed that compounds 3j, 4a, 3c, 3b, and 3h exhibit the most prominent effect against breast cancer cell line with IC50 values of 3.40, 3.50, 3.60, 3.70, and 3.80 µg/ml, respectively using doxorubicin as a control drug. Moreover, molecular docking studies were also performed in order to identify the binding mode mechanism of these compounds with prospective target, thymidylate synthase (PDB:1JU6). On the other hand, the antibacterial activities of all prepared compounds were screened in vitro against three bacterial strains, namely, Escherichia coli, and Pseudomonas aeruginosa as Gram negative bacteria and Staphylococcus aureus as a Gram positive bacterium using agar well diffusion method. The antibacterial activity results revealed that most of the compounds under test were inactive however, among all the tested compounds, only 3g and 4a, in a concentration of 50 µg/ml showed a high antibacterial activity against the three used bacterial strained. It is worthy to note that the potency of 3g against Escherichia coli was comparable to that of the reference drug, while compound 2 exhibited significant activity against Pseudomonas aeruginosa only and compound 3j displayed low activity against Staphylococcus aureus. The structure-antibacterial activity relationship analysis can be modulated by the presence of aromatic or heteroaromatic moiety containing more lipophilic character significantly contributed to antibacterial activity. In addition, the drug-likeness properties have predicted for the target compounds.

Bromelain-based chemo-herbal combination effect on human cancer cells: in-vitro study on AGS and MCF7 proliferation and apoptosis

Abstract Aim. Chemo-herbal combinations promise new clinical anticancer therapeutic modalities. The current study investigated and compared the in vitro effects of a bromelain-based chemo-herbal combination to/with cisplatin or 5-FU, with regard to the proliferation and apoptosis of human gastric AGS and breast MCF7 cell lines. Material and methods. AGS and MCF7 cells were either treated with different concentrations of bromelain, cisplatin or 5-FU; or with bromelain-cisplatin and bromelain-5-FU combinations for 48h. Cell proliferative inhibition and inductive apoptosis were appraised using MTT assay and flowcytometry, respectively. Kruskal-Wallis and Dunn’s tests were used to analyze differences in cell groups’ means. Results. AGS proliferation was adversely affected by single treatments of bromelain and cisplatin (p <0.003) or 5-FU (p <0.05). The anti-proliferative impact of single treatments was more pronounced on MCF7 cells. The bromelain-cisplatin combinations displayed synergistic effect on MCF7 cells (CIs ≤1), while being additive or antagonistic with cisplatin IC30 and IC40 to AGS cell proliferation, respectively. In addition, bromelian-5-FU combinations showed synergistic effect on AGS cells, while antagonistic to MCF7 cells. In terms of cell apoptosis induction, bromelain (IC30)-cisplatin (IC20) displayed additive effect on MCF7, compared to cisplatin single treatment (p <0.04), while bromelain (IC40)-5-FU (IC10) and bromelain (IC30)-5-FU (IC20) afforded additive apoptotic effects on AGS (p <0.04) and MCF7 (p <0.05), respectively, in comparison to 5-FU single treatment. Conclusion. A bromelain-based combination using cisplatin showed concordant effects on cell proliferation impediment and apoptotic induction on MCF7, while the same results were noticed with a bromelain-5-FU combination to AGS cells. The bromelain-based chemo-herbal pathways should further be investigated in the frame of multi-chemotherapeutic drugs researches.

The Interaction Test of Binary Mixtures of Endocrine-Disrupting Chemicals Using In Vitro Bioassays

Typical environmental endocrine-disrupting chemicals (EDCs) such as estradiol valerate (EV), diethylstilbestrol (DES), di-2-ethylhexyl phthalate (DEHP), mono-2-ethylhexyl phthalate (MEHP), and bisphenol A (BPA) have a strong reproductive and developmental toxicity at low concentrations. However, information on their joint toxicity is scarce. In this study, we evaluated the combined effects of EV and other four EDCs (DES, DEHP, MEHP, and BPA) on the human breast MCF-7 cells by detecting the cell proliferation, intracellular reactive oxygen species (ROS) levels, and estrogen receptor alpha (ERα) protein expression using equal concentration ratio method. The results showed that, after exposure for 24, 48, and 72 h, single EV, DES, and BPA can promote the proliferation of MCF-7 human breast cancer cells, and EV has the strongest effect in inducing cell proliferation. DEHP and MEHP cannot induce MCF-7 cell proliferation for all exposure time, while cell proliferation induced by EV was significantly attenuated by DES, BPA, DEHP, and MEHP when they mixed with EV. For intracellular ROS, single EV, BPA, DES, DEHP, and MEHP elevated intracellular ROS levels for different exposure time. Similar to the cell proliferation, DES and BPA decreased intracellular ROS levels induced by EV when they mixed with EV for 24 h. EV, DES, and BPA exposed alone or combined with EV upregulated the ERα protein expression. However, DEHP and MEHP exposed alone or combined with EV had no effect on ERα protein expression, indicating that DEHP or MEHP could attenuate ERα protein expression upregulated by EV. These results showed that the joint toxicity of binary mixtures of EV and other EDCs do not interact in a synergistic fashion in inducing cell proliferation, intracellular ROS levels, and ERα protein expression. These findings have important implications in the human risk assessments of EV mixed with other EDCs in the environment.

Processed Fruiting Bodies of Lentinus edodes as a Source of Biologically Active Polysaccharides

Water soluble polysaccharides (WSP) were isolated from Lentinus edodes fruiting bodies. The mushrooms were previously subjected to various processing techniques which included blanching, boiling, and fermenting with lactic acid bacteria. Therefore, the impact of processing on the content and biological activities of WSP was established. Non-processed fruiting bodies contained 10.70 ± 0.09 mg/g fw. Boiling caused ~12% decrease in the amount of WSP, while blanched and fermented mushrooms showed ~6% decline. Fourier transform infrared spectroscopy analysis (FTIR) confirmed the presence of β-glycosidic links, whereas due to size exclusion chromatography 216 kDa and 11 kDa molecules were detected. WSP exhibited antioxidant potential in FRAP (ferric ion reducing antioxidant power) and ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) assays. Cytotoxic properties were determined on MCF-7 and T47D human breast cell lines using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) test. Both biological activities decreased as the result of boiling and fermenting.

In vitro and in vivo effects of traditional Chinese medicine formula T33 in human breast cancer cells

BackgroundBreast cancer is the leading cause of cancer-related death in women worldwide. Although traditional Chinese medicine (TCM) is commonly used by patients with breast cancer, little is known about TCM prescriptions for breast cancer. This study investigated the effects of a new TCM formula, T33, comprising Radix Kansui, Rheum rhabarbarum, Paeonia lactiflora, Jiangbanxia, and Zhigancao on breast cancer cells in vitro and in vivo.MethodsTo evaluate the effects of T33 on human breast cancer, HMEpiC, MDA-MB231 and MCF-7 cells were treated with different concentrations of T33 and then analyzed using MTT and Transwell migration assays. To elucidate the involvement of autophagy in the T33-induced death of MDA-MB231 and MCF-7 cells, immunofluorescence staining with LC3-II-specific antibodies was performed. Tumor xenografts were generated by subcutaneously injecting either MDA-MB231 or MCF-7 cells into BALB/c nude mice to determine the effects of T33 on these cell lines in vivo.ResultsThe experimental results revealed that 0.1 mg/mL, 0.5 mg/mL, 2.5 mg/mL, 5 mg/mL and 10 mg/mL T33 significantly inhibited the proliferation and invasion of MDA-MB231 and MCF-7 cells. Moreover, significant autophagy was observed in MDA-MB231 and MCF-7 cells in the presence of 2.5 mg/mL, 5 mg/mL and 10 mg/mL T33. An animal study further revealed that both low (200 mg/kg) and high (600 mg/kg) doses of T33 inhibited the proliferation of xenografted breast cancer cells in BALB/c nude mice.ConclusionThese findings demonstrate for the first time that T33 has potential in the treatment of breast cancer owing to its antiproliferative effects and induction of autophagy.

Novel 1,3,4-Triaryl Pyrazoles: Synthesis, QSAR Studies and Cytotoxicity against Breast Cancer

The existence of drug-resistance and lack of selectivity encourages scientists to search for novel and more selective cytotoxic agents. In this work, novel 1,3,4-triarylpyrazole derivatives were synthesized to study their cytotoxicity on MCF7 (human breast Cell Line). In addition, QSAR studies were performed to show the relation between the cytotoxic activity and the structural features of our new synthesized pyrazole derivatives. Pyrazole-4-carbaldehyde derivative 3 was utilized as a starting material for the preparation of the new pyarazole derivatives. These target compounds were screened for their cytotoxic activity against MCF-7 followed by study cell cycle of the most active compounds. Finally, pharmacophore modeling and QSAR Studies was carried out. Among these compounds; 5d and 8b showed the highest anti-proliferative activity (IC50 = 4.9 and 2.11 µM, respectively). Flow cytometric analysis showed that, compounds 5d and 8b arrested the cell cycle in addition to induction of apoptosis in MCF7 cells. Moreover, their stimulation effect on caspases 3/7 was examined to explore their mechanism of induction of apoptosis and the results showed that their proapoptotic activity could be due to the activation of caspases 3/7. Pyrazole derivatives 5d and 8b displayed potent bioactivities, indicating that these compounds could be considered as a new lead for more investigation in the future.

Cell-Viability Analysis Against MCF-7 Human Breast Cell Line and Antimicrobial Evaluation of Newly Synthesized Selenoxopyrimidines

New selenoxopyrimidines were synthesized by one-pot multicomponent reaction of ethyl aceto-acetate, with aromatic aldehydes and selenourea in acidic medium. The synthesized compounds were shown to possess a broad spectrum of antimicrobial activity in vitro. The in vitro anticancer activity of some compounds was studied against MCF-7 human breast cell line using MTT assay. All tested compounds have shown a significant anticancer activity, and 4-phenyl-substituted derivative was found to be most effective anticancer agent (cell viability 50% against 41% for Paclitaxel). The structure-activity relationship (SAR) analysis showed that electron-donating substituents favor anticancer and antibacterial activity and that electron-withdrawing substituents favor antifungal activity.

Effect of germination on anticancer activity of Trigonella foenum seeds extract

Trigonella foenum has a role in cancer treatment. This study tries to evaluate the effect of germination on the anticancer activity of fenugreek seeds. We prepared a dry and germinated aqueous extract from fenugreek seeds. We investigated the growth inhibitory effect of both extracts on MCF7 human breast and Pancreatic (AsPC-1) cells. Fenugreek extracts induced significant effect on cell viability, increased caspase-3 & 6 concentrations and LDH activity and caused nucleosomal DNA fragments. In summary, our results indicated that both dry and germinated extracts induced apoptosis in both cell lines. The effect of germinated extract was higher than that of the dry extract. This can be explained as germination increased the antioxidant characters of the extract. Germination also increased the phytochemical components (flavonoids, tannin, steroids, alkaloids, phytate, phenolics and trigonellin) of the extract which are believed to have anti-tumor activity.