Human MCF-7 Research Articles

Synthesis, structural and spectral characteristics of novel n,π-chelate complexes of Pd(II) and Pt(II) with N-allylthioureas and their influence on the growth of spheroids cells MCF-7 and GGT activity

Four mononuclear n,π-chelate complexes [M(HL1,2)Cl2] (M = Pd2+, Pt2+) have been obtained by the reactions of PdCl2 or K2[PtCl4] with N,N-diethyl-N'-(2-propenyl)thiourea (HL1) or N-cyclohexyl-N'-(2-propenyl)thiourea (HL2) in the presence of HCl. According to X-ray diffraction study, the molecules of HL1,2 are coordinated in a bidentate manner with the formation of six-membered chelate metallocycles in a twist-boat conformation. The diagonal arrangement of “soft-hard” donor atoms (S–M−Cl, C–M−Cl) in the coordination sphere leads to the Pearson's effect of “molecular antisymbiosis in the trans effect” that causes the formation of complexes with an M:L ratio of 1:1. However, interaction in the ratio 1:2, 1:3 is also possible in the solution under the conditions of monodentate coordination of HL1 and HL2. All compounds were investigated by IR, UV–vis and NMR spectra. The 1H/13C NMR study showed that this method is reliable for establishing the formation of a π-coordinating bond. The similarity of the synthesized complexes structure with cisplatin implies the same mechanism of their antitumor action. Thus, it was investigated their effect on the growth and biochemical characteristics of human breast adenocarcinoma cells MCF-7 (grown in three-dimensional culture as spheroids) and the activity of the enzyme gamma-glutamyl transpeptidase (GGT). The results showed that all studied π-complexes are more active compared to cisplatin, and they exhibit pronounced anti-metastatic and pro-apoptotic activity, which one is caused by their inhibitory effect.

In vitro cytotoxic and genotoxic analysis of Garcinia humilis crude extract

Garcinia humilis, known commonly as achachairú or bacupari, has great medicinal value. Their fruits have pharmacological, antibacterial, antioxidant, and anticancer properties. Therefore, the objective of the present study was to evaluate the cytotoxicity and genotoxicity of G. humilis crude extract in breast tumor cells. Cytotoxicity was determined using the Resazurin reduction assay and genotoxicity by the single cell gel electrophoresis assay (Comet assay) on human MCF-7 cells. Crude extract of G. humilis was cytotoxic only when used at high concentrations (IC50 = 5.084 mg mL-1). The Comet assay showed that the crude extract did not induce genotoxicity at 1 and 5 mg mL-1 but did show signs of DNA fragmentation and DNA fragmentation at 10 mg mL-1. The cytotoxic activity against breast adenocarcinoma cells at high concentrations suggests that this medicinal plant could be used with caution and must be further studied to understand better its therapeutic and toxicological potential in the human body.

Graph Theoretical analysis, in silico modeling and molecular dynamic studies of (5-((2-chloropyridin-4-yl)oxy)-3-phenyl-1H-pyrazol-1-yl)-2-(4-substituted phenyl)-N,N-dimethylethen-1-amine derivatives for the treatment of breast cancer.

We synthesized a series of novel amide derivatives of (5-((2-chloropyridin-4-yl)oxy)-3-phenyl-1H-pyrazol-1-yl)-2-(4-substituted phenyl)-N,N-dimethylethen-1-amine [5a-5r] and assessed for their antiproliferative activity against human breast cancer cell line MCF7 by using MTT assay. Graph Theoretical analysis, in silico modeling, molecular dynamic studies, and ADME profile were screened for the synthesized compounds. Based on the observed report, the significant compounds were chosen for their anticancer activity. Graph Theoretical analysis, in silico modeling and molecular dynamic studies of (5-((2-chloropyridin-4-yl)oxy)-3-phenyl-1H-pyrazol-1-yl)-2-(4-substitutedphenyl)-N,N-dimethylethen-1-amine derivatives for the treatment of breast cancer. 5-((2-chloropyridin-4-yl)oxy) (2-phenyl-1H-pyrazol-1-yl)-3-phenyl-1H-pyrazol-1-yl)-3-phenyl-1H-pyrazol-1- (4-substituted phenyl) -N,N-dimethylethen-1-amine [5a-5r] was synthesized using 2-bromo-1-phenylethanone and (5-(2-chloropyridin-4-yloxy)-3-phenyl-1H-pyrazol-1-yl)-N,N-dimethylmethanamine with different aromatic aldehydes and their characterization studies were evaluated by IR, NMR, and mass spectral analysis. The compound 2-(4-methylphenyl)-1-(5-((2-chloropyridin-4-yl)oxy)-3-phenyl-1H-pyrazol-1-yl)-N,N-dimethylethen-1-amine 5a and 2-(2-methylphenyl)-1-(5-((2-chloro pyridin-4-yl)oxy)-3-phenyl-1H-pyrazol-1-yl)-N,N-dimethylethen-1-amine 5c in the amide part exhibited promising cytotoxic activity against all cell lines with IC50 values of 3.3 mM for MCF-7 cells, and produced dramatic cell cycle arrest at EGFR phase as an indicator of apoptotic cell death induction. Based on their high potency in the cellular environment, these straightforward pyrazole-3-carboxamide derivatives may possess the potential to design more potent compounds for intervention with cancer cell proliferation.

Synthesis, biological evaluation and molecular docking studies of novel pyrrolo[2,3-d]pyrimidin-2-amine derivatives as EGFR inhibitors

In the present investigation, we employed pyrrolo[2,3-d] pyrimidine, potassium amide, and liquid ammonia to synthesize pyrrolo[2,3-d]pyrimidin-2-amine derivatives (4a-n). Spectroscopic techniques and elemental analyses were used to determine the structure of the title compounds. For their in vitro cytotoxic activity against the human cancer cell lines MCF-7 (breast), HCT116 (colorectal), and HepG2 (liver), all the synthesized compounds were evaluated. These compounds 4a-n were exhibiting moderate to significant cytotoxic effects against all of the cancer cell lines evaluated. Further, the inhibitory effects of potent compounds (4d, 4e, 4f, 4h, 4i, and 4m) on epidermal growth factor receptor tyrosine kinase (EGFR-TK) were examined. Three compounds, 4d, 4f, and 4h, exhibited good inhibitory effects with IC50 values of 0.107, 0.159, and 0.196 µM, respectively. When potent compounds (4d, 4f, and 4h) were docked into the EGFR-TK protein's active region, it became clear that this protein would be an excellent target for the creation of novel anticancer drugs. All the compounds are compiled with Lipinski's rule of five, which suggests promise for development as oral drug candidates.

Design, synthesis and anticancer evaluation of 1,2,3-triazole linked thiazolo[5,4-d]pyrimidine derivatives as anticancer agents

A novel library of 1,2,3-triazole incorporated thiazolo[5,4-d]pyrimidine ( 10a-j ) derivatives have been designed synthesized and characterized by analytical techniques. Further, these compounds ( 10a-j ) were examined for their in vitro anticancer application towards four different types of human cancer cell lines PC3 (prostate cancer), A549 (lung cancer), MCF-7 (breast cancer) and A2780 (ovarian cancer) by the use of MTT method and the clinically proved drug etoposide used as standard reference. Among the examined compounds, five compounds 10a, 10e, 10f, 10i and 10j displayed more potent activities. Predominantly, compound 10e demonstrated most promising anticancer activity.

Cytotoxicity, Phytochemical Screening and Genetic analysis of Ginger (Zingiber officinale Rosc.) Callus and Rhizome

• Ginger rhizome extracts displayed strong cytotoxic effect against HT29, HT116 and MCF-7 cancer cells lines with highest activity against HT29. • Ginger callus extracts recorded non-cytotoxic effect against all examined cancer cells with IC50 >100 µg/mL. • Ginger rhizome extracts contained more phenols and terpenes than the callus ones. • The principal components of ginger; 6-gingerol and 6-shogaol were not detected in callus extracts. • Incidence of genetic changes in DNA of ginger callus during in vitro culture in 2,4-D containing medium. • Most polymorphic bands (11 out of 12) were generated in callus during in vitro culture with total polymorphism 23.07% between callus and plant. Ginger ( Zingiber officinale Rosc.) is well known as distinctive spice with considered therapeutic values. In the current work we aimed to investigate cytotoxic effect, phytochemical screening and genetic analysis of ginger callus and their rhizome. Cytotoxicity of ginger rhizome and callus extracts was examined against some human cancer cell lines HT29, HT116 and MCF-7 by MTT method. Phytochemicals were screened by thin layer chromatography (TLC) and genetic analysis was performed by ISSR markers. Ginger rhizome principle components, 6-gingerol and 6-shogoal were used as standards to detect their presence in callus. Results showed that, rhizome extracts displayed a strong cytotoxicity towards all tested cancer cells with the highest activity (IC 50 20.4 ± 3.0 µg/mL; P< 0.05) against HT29. IC 50 of ginger callus extracts were >100 µg/mL in all examined cancer cell lines. TLC chromatograms of rhizome and callus extracts revealed the presence of phenols and terpenes, whereas 6-gingerol and 6-shogaol were only detected in rhizome extracts. Genetic analysis by ISSR markers revealed occurrence some genetic changes in DNA of callus compared to that of rhizome with total polymorphism 23.07%. In conclusion, ginger cytotoxicity to HT29, HT116 and MCF-7 cancer cells was mainly associated with the presence of 6-shogaol and 6-gingerol in extracts, which appeared as strong cytotoxic effect in rhizome compared to non-cytotoxic effect was evaluated in the callus extracts. Therefore, further studies on the callus elicitation and precursors feeding to induce biosynthesis of ginger bioactive molecules are recommended.

Evaluation of antimicrobial activity of thiolated methylated N-(4-N,N-dimethylaminobenzyl) chitosan as a new derivative of chitosan

Despite chitosan, a natural cationic polysaccharide derived from chitin, being applied as an antimicrobial agent, many studies are being performed for enhancing its capability to fight against pathogens. The aim of this study was to investigate the antibacterial effect of thiolated methylated N-(4-N,N-dimethylaminobenzyl) chitosan (TTMAC) polymer and its nanoparticles as a novel derivation of chitosan. The polymer derivative was synthetized and characterized via 1 H NMR, Fourier transform infrared and the Elman test. The nanoparticles with different N/P ratios were prepared by the ionic gelation method and were characterized by dynamic light scattering and transmission electron microscopy. The cellular toxicity of polymer and nanoparticles at different concentrations were evaluated on human MCF-7 cell line. Antimicrobial assay was performed on Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 25923) and Candida albicans (ATCC 10231) as Gram-negative, Gram-positive and yeast pathogens, respectively. The obtained results have shown the TTMAC polymer has a higher inhibition activity against microbial pathogens and also lower cellular toxicity in comparison with chitosan polymer. Furthermore, chitosan nanoparticles in comparison with TTMAC nanoparticles have lower size and highest zeta potential in different ratio and chitosan nanoparticles have more inhibitory effects against microbial pathogens. In conclusion, TTMAC derivative in polymeric form can be a promising tool against microbial pathogens.

Synthesis, Characterization and Cytotoxicity Activity Study of Some Chalcones Derived from 2-(1,1-dimethyl-1,3-dihydro-2H-benzo[e]indol-2-ylidene)malonaldehyde

In this work, series of new chalcones derived from indole compounds were synthesized. In the first the compound 2-(1,1-dimethyl-1,3-dihydro-2H-benzo[e]indol-2-ylidene)malonaldehyde was synthesized from the reaction of 1,1,2-trimethyl-1H-benzo[e]indole with Phosphoryl chloride in in the presence of (DMF). Schiff base (C2) was prepared by reaction of 2-(1,1-dimethyl-1,3-dihydro-2H-benzo[e]indol-2-ylidene) malonaldehyde with 3-amino acetophenone and then the compounds (C3-C6) were synthesized by reacting compound (C2) with a different aryl aldehyde in the presence of potassium hydroxide. The chemical composition of the compounds was confirmed and characterized by spectroscopic techniques (FT-IR, 1H-NMR and13C-NMR). Target compounds with different concentrations were investigated for their cytotoxic activity against the human breast cancer cell line MCF7. The results showed that the compounds had promising cytotoxic activity against MCF7 cell line especially compound (2) which showed the highest inhibition at the rate of 100 µg/mL among the tested compounds at varied concentrations.

Synthesis and Anti-Tumor Effects of Novel Pomalidomide Derivatives Containing Urea Moieties.

In order to explore novel immunomodulatory agents as anti-tumor drugs, we designed and synthesized a series of new pomalidomide derivatives containing urea moieties. Interestingly, in vitro biological experiments performed in several cancer cell lines showed that some of them displayed potent anti-tumor ability. These novel compounds 5a-5e and 6a-6e demonstrated the best cell growth inhibitive activity in human breast cancer cell lines MCF-7, but weaker inhibitive activity in human hepatocellular carcinoma cell lines Huh7. Moreover, compound 5d had the most powerful effects in this study, with an IC50 value of 20.2 μM in MCF-7. Further study indicated that compound 5d could inhibit cell growth and induce cell death in a concentration-dependent manner. Besides, compound 5d increased cellular ROS levels and induced DNA damage, thereby potentially leading to cell apoptosis. These observations suggest that the novel pomalidomide derivatives containing urea moieties may be worth further investigation to generate potential anti-tumor drugs.

4-oxoquinoline-3-carboxamide acyclonucleoside phosphonates hybrids: Human MCF-7 breast cancer cell death induction by oxidative stress-promoting and in silico ADMET studies

Breast cancer is the leading cause of cancer death in women. Although the available treatments are efficient, cancer cells promptly develop resistance to different drugs, leading to disease relapse and promoting tumor progression. Here, novel 4-oxoquinoline-3-carboxamide acyclonucleoside phosphonate hybrids were synthesized as antitumoral agents, and in silico toxicity screening were performed. Derivatives 15c, 15e, 15g, and 15k showed significant cytotoxicity where 15c induces the most considerable loss of cell viability through the apoptotic process, while 15k induces cell death by necrosis. All compounds, except 15e, induced the production of OH- and NO, besides increasing the levels of superoxide ions. In silico toxicity studies showed that 15g presented low hepatotoxicity risk and probability as BCRP substrate. These findings point out that derivative 15g is a potential candidate for an optimization program for the development of new anticancer agents.

Microwave-Induced CuO Nanorods: A Comparative Approach between Curcumin, Quercetin, and Rutin to Study Their Antioxidant, Antimicrobial, and Anticancer Effects against Normal Skin Cells and Human Breast Cancer Cell Lines MCF-7 and T-47D.

Herein, we explore the biological properties of curcumin, quercetin, and rutin by loading them onto porous CuO nanorods (NRs). The CuO NRs were synthesized using the microwave irradiation method through a chemical reaction between CuSO4·5H2O and NaOH in the presence of the anionic stabilizer sodium dodecyl sulfate. The shape and surface morphology of CuO NRs were examined with two microscopic techniques: high-resolution transmission electron microscopy (HR-TEM) and field emission scanning electron microscopy (FESEM). Their average diameter was measured by TEM to be 15 ± 2 nm. The porosity and interfacial area of the fabricated material were determined by Brunauer-Emmett-Teller analysis. After successful synthesis, CuO NRs were loaded with polyphenolic curcumin, quercetin, and rutin, with the loading efficiency of 57.8, 62.2, and 81.2%, respectively, which was confirmed by UV-visible and infra-red spectroscopy and finally with a thermal gravimetric technique. Their radical scavenging activity was measured with the 2,2-diphenyl-1-picrylhydrazyl radical and compared with the control (ascorbic acid). Further, good bactericidal effects were observed against both Gram-positive bacterial strains, including Staphylococcus aureus and Bacillus subtilis, and Gram-negative bacterial strains, including Salmonella typhi, Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae. Excellent anticancer activity was observed against normal skin cells and breast cancer cells T-47D and MCF-7.

Structure modification and anti-tumor activity evaluation on sesquiterpene lactones TBA and TBB from Sphagneticola trilobata

Thirteen sesquiterpene lactone derivatives were designed and synthesised using the sesquiterpene lactone epimers TBA and TBB as the parent molecules, isolated from Sphagneticola trilobata. Their structures were elucidated by extensive spectroscopic studies and chemical evidence. Furthermore, the structures of 1a, 4b and 5a were confirmed by X-ray single-crystal diffraction analyses. All of the compounds were further examined for their in vitro antiproliferative activity against human cancer cell lines HeLa and MCF-7. Unfortunately, the activity of all derivatives were weaker than that of the parental compounds.

Exploration of thiazolidine-2,4-diones as tyrosine kinase inhibitors: Design, synthesis, ADMET, docking, and antiproliferative evaluations.

As dual EGFR and VEGFR-2 inhibitors, 22 innovative thiazolidine-2,4-diones were modeled, constructed, and measured for their anticancer performance versus four human neoplasms HCT-116, MCF-7, A549, and HepG2. Molecular docking and MD simulation were performed to inspect the binding technique of the proffered congeners with the EGFR and VEGFR-2 receptors. Evidence realized thanks to the docking inquests was vastly consistent together with that detected through the biological screening. Structures 14a and 14g emerged as the most active compounds toward HCT116 (IC50 = 6.01 and 7.44 µM), MCF-7 (IC50 = 5.77 and 7.23 µM), A549 (IC50 = 5.35 and 5.47 µM) and HepG2 (IC50 = 3.55 and 3.85 µM) tumefaction cells. Compounds 14a and 14g exhibited higher events than sorafenib (IC50 = 5.05, 5.58, 4.04, and 4.00 µM) against HepG2 instead subordinate incidents concerning A549, MCF-7, and HCT116, parallelly. Nevertheless, these compounds signified weightier performance than erlotinib (IC50 = 13.91, 8.20, 5.49, 7.73, and µM), with respect tothe four cell lines. Compounds having the best activity against the four cell lines, 12a-f, 13a-d, and 14a-gwere chosen to appraise their in vitro VEGFR-2 and EGFRT790M inhibiting activities. The best results were for compounds 14a and14g compared to sorafenib and erlotinib, respectively, with IC50 values of 0.74 and 0.78 µM and 0.12 and 0.14 µM, respectively. Moreover, 13d, 14a, and 14g showed an adequate in silico calculated ADMET profile. The current investigation presents novel candidates for future optimization to construct mightier and eclectic binary VEGFR-2/EGFRT790M restrainers with higher antitumor effects.

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.

Isolation, Characterization and Anticancer Activity of Two Bioactive Compounds from Arisaema flavum (Forssk.) Schott.

Medicinal plants play important role in the public health sector worldwide. Natural products from medicinal plants are sources of unlimited opportunities for new drug leads because of their unique chemical diversity. Researchers have focused on exploring herbal products as potential sources for the treatment of cancer, cardiac and infectious diseases. Arisaema flavum (Forssk.) is an important medicinal plant found in the northwest Himalayan regions of Pakistan. It is a poisonous plant and is used as a remedy against snake bites and scorpion stings. In this study, two bioactive compounds were isolated from Arisaema flavum (Forssk.) and their anticancer activity was evaluated against human breast cancer cell line MCF-7 using an MTT assay. The crude extract of Arisaema flavum (Forssk.) was subjected to fractionation using different organic solvents in increasing order of polarity. The fraction indicating maximum activity was then taken for isolation of bioactive compounds using various chromatographic and spectroscopic techniques such as column chromatography, thin-layer chromatography (TLC), gas chromatography-mass spectrometry (GC-MS), Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR). Crude extract of Arisaema flavum (Forssk.), as well as various fractions extracted in different solvents such as n-hexane, chloroform and ethyl acetate, were tested against human breast cancer cell line MCF-7 using an MTT assay. The crude extract exhibited significant dose-dependent anticancer activity with a maximum activity of 78.6% at 500 µg/mL concentration. Two compounds, hexadecanoic acid ethyl ester with molecular formula C18H36O7 and molar mass 284 and 5-Oxo-19 propyl-docosanoic acid methyl ester with molecular formula C26H50O3 and molecular mass 410, were isolated from chloroform fraction. These compounds were tested against the MCF-7cell line for cytotoxic activity and exhibited a significant (p &lt; 0.00l) decrease in cell numbers for MCF-7 cells with IC50 of 25 µM after 48 h of treatment. Results indicated that Arisaema flavum (Forssk.) possesses compounds with cytotoxic activity that can further be exploited to develop anticancer formulations.

Induction of oxidative DNA damage, cell cycle arrest and p53 mediated apoptosis by calcium titanate nanoparticles in MCF-7 breast cancer cells

BackgroundThe distinctive properties and high activity of calcium titanate nanoparticles (CaTiO3-NPs) increase their use in many products. However, the cytotoxic and genotoxic effects of CaTiO3-NPs in human cancer cell lines have not been well studied. Therefore, this study was conducted to explore CaTiO3-NPs induced cytotoxicity, genomic instability and apoptosis in human breast cancer (MCF-7) cells.MethodsSulforhodamine B (SRB) and the alkaline comet assays were done to study cell viability and DNA damage induction, respectively. Apoptosis induction and cell cycle distribution were analyzed using flow cytometry. The level of intracellular reactive oxygen species (ROS) was studied, and the expression levels of p53, Bax and Bcl2 genes were also measured.ResultsThe results of the Sulforhodamine B (SRB) cytotoxicity assay showed that viability of MCF-7 cells was not affected by CaTiO3-NPs treatment for 24 h, however, exposure to CaTiO3-NPs for 72 h caused concentrations dependent death of MCF-7 cells. Treatment with CaTiO3-NPs for 72 h caused marked increases in intracellular ROS level and induced DNA damage. Treatment of MCF-7 cells with CaTiO3-NPs also caused MCF-7 cell cycle arrest at the G0 and S phases and s triggered apoptosis of MCF-7 cells by causing simultaneous increases in the expression levels of apoptotic p53 and Bax genes and a decrease in the expression level of anti-apoptotic Bcl2 gene.ConclusionCollectively, it was concluded that CaTiO3-NPs cause time- and concentration-dependent cytotoxic effects in human MCF-7 cells through induction of ROS generation, genomic instability and apoptosis. Thus it is recommended that further in vitro and in vivo studies are therefore recommended to understand the cytotoxic and biological effects of CaTiO3-NPs.

S-phase arrest and apoptosis in human breast adenocarcinoma MCF-7 cells via mitochondrial dependent pathway induced by tricyclohexylphosphine gold (I) n-mercaptobenzoate complexes

We have previously reported the inhibition of thioredoxin reductase (TrxR) and invasion by tricyclohexylphosphine gold (I) n-mercaptobenzoate (n = 2, 3, 4) labeled as 1–3 towards MCF-7 cells, in vitro. Nevertheless, the mode of death and its apoptotic pathway has yet to be revealed. The main aim of this study is to investigate the anti-neoplastic activity of this phosphanegold (I) thiolates against breast adenocarcinoma cells, MCF-7. Herein, we explored the role of gold(I) series, 1–3 for their apoptosis-inducing ability against MCF-7 cells. They were scrutinized for their antiproliferative activities which exhibited their IC50 values of 8.14 μM ± 0.10, 7.26 μM ± 0.33, and 9.03 μM ± 0.69, respectively, and indicated better cytotoxicities than that of cisplatin (positive control). Further, the mechanisms of their actions were studied by analyzing the status of ROS generation (by DCFH-DA), cytochrome c release (by ELISA), and activation of caspases 3/7, 8, 9, and 10, annexin V staining and cell cycle analysis by flow cytometry, respectively. It was observed that the compounds, 1–3 can promote ROS generation, cytochrome c release, and activation of caspases 3/7, caspase 8, caspase 9, and caspase 10 on MCF-7 cells. In addition, the compounds are shown to induce MCF-7 cell arrest at S-phase. Gene analysis via PCR array further clarified their effects by modulating the related genes upon the compounds' treatment. Further investigation on other breast cancer cells as well as in vivo studies on these compounds will further increase their potential as anti-breast cancer agents.

Colchicine of Colchicum autumnale, A Traditional Anti-Inflammatory Medicine, Induces Apoptosis by Activation of Apoptotic Genes and Proteins Expression in Human Breast (MCF-7) and Mouse Breast (4T1) Cell Lines.

Breast cancer is one of the major causes of mortality among women. Due to many side effects of the existing chemotherapeutic agents, the research of anti-cancer drugs, including natural products, is still a big challenge. Here, we investigated the effects of colchicine on apoptosis of two breast cancer cell lines ( human MCF-7 and mouse 4T1). In this experimental study, we evaluated the apoptotic effects of colchicine on (MCF-7) and (4T1), as well as a human cancer-associated fibroblast cell line as a control group. Extraction and chromatographic techniques were applied to isolate colchicine from Colchicum autumnale L. To compare the isolated colchicine with pure standard colchicine, we used the H-NMR technique. The methyl thiazolyl tetrazolium (MTT) assay, quantitative reverse transcriptase-polymerase chain reaction, Western blotting and annexin V/PI staining were used to evaluate the apoptotic effects of the isolated and standard colchicine. Similar to standard colchicine, the isolated colchicine inhibited cell proliferation significantly in cancer cell lines. Colchine inhibited proliferation and induced apoptosis on a dose-dependent manner. The medicine modified the expression of genes-related to apoptosis by up-regulation of P53 ,BAX, CASPASE-3, -9 and down-regulation of BCL-2 gene, which led to an increase in the BAX/BCL-2 ratio. We showed that isolated colchicine from Colchicum autumnale and pure standard colchicines modulate the expression levels of several genes and therefore exerting their anticancer effects on both human (MCF-7) and mouse (4T1) breast cancer cells. Based on these results, we suggest that colchicine can be a potential candidate for prevention and treatment of breast cancer.

Directional screening and identification of potential cytotoxic components from Achnatherum inebrians by a combination of surface palsmon resonance and chromatography

ObjectiveTo establish a method for directional screening of the cytotoxic components from the medicinal herb of Achnatherum inebrians by a combination of surface plasmon resonance (SPR) biosensor and chromatographic isolation technology. MethodsUnder the guidance of bioactive assessment based on binding abilities between objects and the α-Mannosidase (α-Man) target, the active components from different solvents extracts, different polar extraction parts and fractions were screened orderly and directionally using SPR. Components with a high binding ability to α-Man can be precisely oriented in a narrower fractions range and are easy to isolate. Three human cancer cells were used to evaluate the cytotoxic activity of component with the highest affinity to α-Man. ResultsEight compounds were isolated and identificated from A. inebrians for the first time. Deoxyvasicinone possessed the highest affinity to α-Man among them. Moreover, deoxyvasicinone showed good effects on inhibited proliferation of human hepatoma cells HepG2 (IC50 = 5.7 μmol/L), human breast cancer cells MCF7 (IC50 = 7.21 μmol/L) and human lung cancer cells HCC827 (IC50 = 0.75 μmol/L), respectively. In particular, its inhibitory effect on HCC827 was stronger than the positive drug gefitinib (IC50 = 1.65 μmol/L). ConclusionA comprehensive strategy of directional screening potential cytotoxic components from herb based on biomolecular interaction and chromatography was established. Deoxyvasicinone as an effective anti-cancer component was initially isolated from A. inebrians. It is expected that this screening strategy could provide new perspectives for rapid screening and identification of active components from natural plants with the complex matrix.

Impact of DC glow discharge plasma treated Ti doped hydroxyapatite nanomaterials using antibacterial and cytotoxicity applications

In this work we developed Ti doped hydroxyapatite with were synthesized by using a solgel technique with exposed to DC glow discharge plasma with different times treated. The pure and Ti/HAp were characterised by using different characterizations like XRD, FTIR, SEM, EDAX, UV-visible, PL, TG-DTA, antibacterial activity, 3T3 fibroblast cells and MCF-7 breast cancer cell line with cytotoxity efficiency analysis. The pure HAp and Ti/HAp materials had a nanocube and nanoflakee shape in the SEM results. In the ultraviolet-visible light (UV-vis) spectrum, the band edge absorption of bare HAp and Ti/HAp samples is discovered at wavelengths of 295 nm and 328 nm, respectively. The antibacterial activity of untreated and plasma-treated pure HAP and Ti/HAp samples are tested against two gram-positive bacteria, Bacillus cereus and Staphylococcus aureus, as well as two gram-negative bacteria, E. coli and Pseudomonas aeruginosa, using the agar well diffusion technique. The MTT assay was used to investigate the mean per cent (% percent) cell survival of Ti/HAp at various concentrations (6 mg/mL; 85 mg/mL) against 3T3 fibroblast cells and human MCF-7 Breast cancer cell lines. The synthesised Ti/HAp biocompatibility makes it a viable contender for future biological uses.