Human Breast Adenocarcinoma Cell Line Research Articles

Responses of human colon and breast adenocarcinoma cell lines (LoVo, MCF7) and non-tumorigenic mammary epithelial cells (MCF-10A) to the acellular fraction of packed red blood cells in the presence and absence of cisplatin.

Perioperative blood transfusion in colorectal and some other cancer patients has been linked to the increased risk for recurrence, but a causal mechanism remains unclear. During the preparation and storage of packed red blood cells (PRBCs) bio-active substances accumulate in the acellular fraction (supernatant). Viability, proliferation, reactive oxygen species (ROS) levels, and DNA damage of colon (LoVo) and breast (MCF7) adenocarcinoma cells and non-tumorigenic MCF-10A cell line were determined in response to the supernatants of fresh and long-stored (day 42) PRBCs, leukoreduced (LR) or non-leukoreduced (NLR). The effect of supernatants on the cytotoxicity of cisplatin (cisPt) towards the cells was also examined. Supernatants, especially from a day 1 PRBCs, both LR and NLR, reduced the viability and inhibited proliferation of tumor cells (LoVo, MCF7), accompanying by the excessive ROS production, but these were not the case in MCF-10A. Moreover, supernatants had no effect on the cytotoxicity of cisPt against LoVo and MCF7 cells, while caused increased drug resistance in MCF-10A cells. The findings suggest the acellular fraction of PRBCs does not exhibit any pro-proliferative activity in the cancer cell lines studied. However, these are pioneering issues and require further research.

Abstract 3804: Interferon gamma induces NOS2 and COX2 expression in estrogen receptor negative breast cancer leading to immunosuppressive tumor microenvironment

Abstract Breast cancer is the second leading cause of cancer death among U.S. women although the mortality is on a steadily decreasing trend since early 90s. We previously demonstrated a strong correlation between elevated NOS2 and COX2 expressions suggesting these genes can serve as markers of poor prognosis in estrogen receptor negative (ER-) breast cancer. In other words, NOS2 and COX2 is generally associated with the immune response. Induction of NOS2 and COX2 has also been shown to orchestrate multiple pro-oncogenic pathways that may contribute to the immunosuppressive nature of cancer cells. To better understand the interactions between cytokines and breast cancer cells and develop effective therapeutics for breast cancer, we examined the effects of selected cytokines on MDA-MB-231, a human (ER-) breast adenocarcinoma cell line. We found that in combination with cytokines, such as IFNG plus TNF, IL1B, or IL17, significantly induced NOS2 and COX2. IFNG plus TNF or IL1B most strongly induced NOS2 and COX2 where IFNG or IL17 to a lesser extent. It indicates that expressions of NOS2 and COX2 required IFNG but at a low dose in presence of other cytokines. Single-cell RNAseq analysis shows that cells treated with IFNG plus TNF or IL1B clustered with those expressed NOS2 and COX2 as revealed in tSNE plots. Expression of other factors such as IL8 and IL6 (suggested markers for prognosis of breast cancer) or PDL1 and IDO1 (suggested cancer therapeutic targets) also co-clustered with NOS2 and COX2 expressions. In addition, we found increased IL1A and IL1B expressions provide fortification to NOS2 and COX2 expressions. Taken together, our current findings indicate the interactions between breast cancer cells and cytokines. We believe further spatial transcriptomic and proteomic studies may be beneficial for clarifying the complex networks of the immunosuppressive tumor microenvironment. Citation Format: Yuk Sing Robert Cheng, Lisa Ridnour, Veena Somasundaram, Dana Bhattacharyya, Christopher McGinity, Daniel McVicar, Stephen Anderson, Stephen Lockett, David Wink. Interferon gamma induces NOS2 and COX2 expression in estrogen receptor negative breast cancer leading to immunosuppressive tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3804.

Vlasouliodes A-D, four new C30 dimeric sesquiterpenes exhibiting potential inhibition of MCF-7 cells from Vladimiria souliei

As our ongoing interest to search bioactive dimeric sesquiterpenes from the genus Vladimiria (Asteraceae), the plant of Vladimiria souliei was studied. Based on the repetitive chromatographic fractionation, a chemical investigation on the roots of Vladimiria souliei led to the isolation and the identification of four previously undescribed sesquiterpene dimers, vlasouliodes A-D (1–4). Their chemical structures were elucidated by comprehensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR spectroscopic data. The absolute configurations of them were unambiguously established by the experimental and calculated ECD data. In the in vitro biological activity evaluation, 1 and 3 displayed pronounced inhibitory activity against human breast adenocarcinoma cell lines (MCF-7) with IC50 values of 17.12 ± 0.42 μM and 13.12 ± 0.10 μM, respectively. Additionally, treatment with 1 and 3 induced cell apoptosis in MCF-7 cells, down-regulated the expression of Caspase-3 and up-regulated the expression of Cleaved-caspase-3.

Dual-targeted and controlled release delivery of doxorubicin to breast adenocarcinoma: In vitro and in vivo studies

Doxorubicin (DOX) is a chemotherapeutic drug that belongs to the anthracyclines family. Cardiotoxicity is one of the main limiting factor of prescribing DOX. To reduce its side effects and enhance the drug delivery to the targeted tissues, we aimed to establish a new targeted and controlled release drug delivery system for treatment of breast cancer. In this article, we tried to synthesize a new nanoplatform consisted of DOX conjugate with hydrazide and disulfide bonds to the hyaluronic acid (HA). Firstly, 4,4′-Dithiodibutyric acid (DTBH) was conjugated with HA. Then, 3-aminophenyl boronic acid monohydrate (APBA) was conjugated with DTBH-HA. Subsequently, DOX was added to DTBH-HA-APBA. HA is a natural polymer with the ability to target CD44, a cell surface adhesion receptor, which are highly overexpressed on the surface of variety of cancer cells. Other targeting agent, APBA can target sialic acid on the cancer cells surface and improve the tumor uptake. Formation of The DTBH-HA-APBA conjugate was confirmed by proton nuclear magnetic resonance (1H NMR) spectroscopy. Scanning emission electron microscopy (SEM) images of the DOX-DTBH-HA-APBA displayed a spherical shape with an average diameter of about 70 nm. In vitro drug release study showed considerably different release pattern of DOX from the formulation at acidic pH (5.4) which was higher than normal pH (7.4). Cellular uptake and cellular cytotoxicity analysis were examined in human breast adenocarcinoma cell line (MCF-7) and mouse breast cancer cells (4T1) as positive cell lines and Chinese Hamster Ovary cells (CHO) as negative cell line. Results confirmed that there is a remarkable difference between dual-targeted (DOX-DTBH-HA-APBA) and single targeted (DOX-DTBH-HA) formulations in both positive cell lines regarding internalization and cytotoxicity. In vivo studies indicated that dual-targeted formulation has the best efficacy with minimum side effects in mouse model. Fluorescence imaging of organs revealed that DOX-DTBH-HA-APBA showed greater DOX accumulation compared with DOX-DTBH-HA and free DOX in tumor site. Also, pathological evaluation indicated that there is no observable cardiotoxicity with final formulation.

Acute toxicity and antitumor potential of 1,3,4-trisubstituted-1,2,3-triazole dhmtAc-loaded liposomes on a triple-negative breast cancer model.

For the first time, compounds developed from the 1,2,3-triazole scaffold were evaluated as novel drugs to treat triple-negative breast cancer (TNBC). Four organic salts were idealized as nonclassical bioisosteres of miltefosine, which is used in the topical treatment for skin metastasizing breast carcinoma. Among them, derivative dhmtAc displayed better solubility and higher cytotoxicity against the human breast adenocarcinoma cell line and mouse 4T1 cell lines, which are representatives of TNBC. In vitro assays revealed that dhmtAc interferes with cell integrity, confirmed by lactate dehydogenase leakage. Due to its human peripheral blood mononuclear cell (PBMC) toxicity, dhmtAc in vivo studies were carried out with the drug incorporated in a long-circulating and pH-sensitive liposome (SpHL-dhmtAc), and the acute toxicity in BALB/c mice was determined. Free dhmtAc displayed cardiac and pulmonary toxicity after the systemic administration of 5 mg/kg doses. On the other hand, SpHL-dhmtAc displayed no toxicity at 20 mg/kg. The in vivo antitumor effect of SpHL-dhmtAc was investigated using the 4T1 heterotopic murine model. Intravenous administration of SpHL-dhmtAc reduced the tumor volume and weight, without interfering with the body weight, compared with the control group and the dhmtAc free form. The incorporation of the triazole compound in the liposome allowed the demonstration of its anticancer potential. These findings evidenced 1,3,4-trisubstituted-1,2,3-triazole as a promising scaffold for the development of novel drugs with applicability for the treatment of patients with TNBC.

Effect of the elastin-derived peptides (VGVAPG and VVGPGA) on breast (MCF-7) and lung (A549) cancer cell lines in vitro

Tissues are subjected to dynamic communication between cells and the extracellular matrix (ECM), resulting in ECM remodeling. One of the ECM components is elastin, which releases elastin‐derived peptides (EDPs) during the aging process. Therefore, the aim of the present study was to evaluate the impact of the VGVAPG hexapeptide and elastin-like peptide VVGPGA (control) on certain metabolism parameters in human breast adenocarcinoma (MCF-7) and human lung carcinoma (A549) cell lines. The results did not show a significant effect of the peptides on metabolic activity and caspase-3 activity. However, more specific analysis revealed that VGVAPG and VVGPGA were able to increase KI67 protein expression in both tested cell lines after 24-h treatment. Moreover, the same correlation was observed at the KI67 gene level. VGVAPG also increased the P53, ATM and SHH gene expression in the A549 cells up to 19.08%, 20.74%, and 28.77%, respectively. Interestingly, the VGVAPG peptide exerted an effect on the expression of antioxidant enzymes SOD2 and CAT in the A549 and MCF-7 cells, especially after the 24-h treatment. Lastly, both peptides influenced the CAV1 and CLTC1 expression. Our results show that the tested EDPs have an effect on both A549 and MCF-7 cells at the cellular level. This may be correlated with the multidrug-resistance (MDR) phenotype in these cancer cells, which is an emerging problem in the current anticancer treatment. However, more research is needed in this field.

3D Bioprinted Artificial Breast Cancer Tumor Disks: A New Tool for Understanding Intra‐tumor Heterogeneity?

Recently the UWRF Tissue and Cellular Innovation Center and the Century College Biofabrication Program have engaged in a series of new collaborative research projects using bioprinting technology and methods to model and study in‐vitro 3D artificial tumor and stromal tissues. In this presentation, we report on results obtained from efforts to bioprint cancer disks using the human breast adenocarcinoma cell line MCF‐7. This breast cancer cell line is considered to be one of the “gold standard” cultures to study this type tumor. In extensive previous studies in our lab using other 3D modeling methods, we have established a robust library of experience and data with these cells and artificial tissue constructs. In these new studies, bioprinting methods were applied to establish tumor structures which initially contained specific cell numbers per unit volume as well as relatively mono‐cellular distribution patterns. Both of these characteristics had been very difficult to predictably generate and control in earlier studies using precast or molded hydrogels made of chitosan and hyaluronic acid or decellularized natural marine sponge ECM. In this project, two distinct bioinks were tested including one called GelMa, a gelatin/methacrylate hydrogel and another called GelMa‐C which is basically the same, but with nanocellulose added to enhance the structural stability of constructs during printing. While both bioinks generated structures and tissues, the GelMa bioink specifically generated relatively transparent tumor structures that provided a unique window into the cell interactions and eventual early development of these artificial tumor tissues. Using a Cellink “Inkcredible” model printer loaned to the TCIC by Century College for the duration of this project, we printed tumor disks with a diameter of 5 mm and thickness of 2.5 mm and then cultured these in 6 well plates for up to 3 months. These breast cancer disks displayed features and tissue progression similar to that seen with the other methods used in our earlier work, while also providing new and unique insights into the interior artificial tumor tissue development in real‐time. These new observations also demonstrated a unique cell/tissue behavior in the resulting constructs that we hypothesize may directly address the origins of intra‐tumor heterogeneity of various cell subpopulations and their relative contributions to the overall tumor development. Future studies are planned to further evaluate and qualify these observations and to apply this new 3D artificial tissue tool to further elucidate cancer biology as a whole.

Polymer microspheres modified with pyrazole derivatives as potential agents in anticancer therapy – Preliminary studies

The methods of fighting cancer are far from ideal, therefore it is necessary to search for innovative and effective drugs. In our work, we present pyrazole derivatives and their modifications with polymer microspheres as potential anticancer agents. Molecular and crystal structures of pyrazole derivatives were determined an X-ray analysis and characterized by theoretical calculations. Modifications of cross-linked polymer microspheres with pyrazole derivatives were made on the basis of divinylbenzene and glycidyl methacrylate. The in vitro antiproliferative activity of the pyrazole derivatives and their modified microspheres was assessed against a normal cell line, namely monkey epithelial renal cells (GMK) and cancer cell lines, such as human hepatocellular carcinoma cell line (HepG2), human breast adenocarcinoma cell line (MCF-7) as well as human lung adenocarcinoma cell line (A549), using the MTT assay. All the tested pyrazole derivatives and the polymer microspheres modified by them showed antiproliferative activity in vitro. Two of the modified substances showed the greatest ability to inhibit divisions of all cancer cells. In order to determine a potential target, molecular docking was performed. In silico studies carried out with the use of the human EphB1 receptor revealed that the analyzed compounds bound to the EphB1 binding site, and the compounds with the highest antiproliferative activity showed a better fit to the active site.

Altersolanol B, a fungal tetrahydroanthraquinone, inhibits the proliferation of estrogen receptor-expressing (ER+) human breast adenocarcinoma by modulating PI3K/AKT, p38/ERK MAPK and associated signaling pathways

The present study focused on the apoptosis-inducing effects and cellular signal-modulating properties of altersolanol B (AB), a minor fungal tetrahydroanthraquinone (THAQ) metabolite, in the estrogen receptor positive (ER+) human breast adenocarcinoma cell line, MCF-7. AB demonstrated approximately 4-fold greater antiproliferative activity in ER+ MCF-7 cells (IC50 5.5 μM) compared to the ER-negative (triple-negative) MDA-MB-231 (IC50 21.3 μM). The viability of normal breast fibrocystic epithelial cells, MCF-10A, was unaffected. AB induced intrinsic apoptosis in MCF-7 cells; it triggered the activation of caspase 9 and poly (ADP-ribose) polymerase (PARP), upregulated the expression of pro-apoptotic Bax, and downregulated the expression of anti-apoptotic Bcl-2. AB induced cell cycle arrest at G0/G1, as indicated by the downregulation of key checkpoint proteins operating at the G0/G1 phase of the cell cycle (cyclin D1, CDK4 and CDK2). The observed increase in p21Waf1/Cip1 and p53 expression may facilitate cell cycle arrest, and the subsequent induction of apoptosis. AB lacked significant effects on intracellular ROS levels, while it down-regulated nuclear factor erythroid 2-related factor 2 (Nrf2), and the Nrf2-dependent antioxidant enzyme, heme oxygenase-1. The compound disrupted AKT signaling through the downregulation of phospho-AKT and phospho-FOXO1, and the upregulation of PTEN, a phosphatase and tumor suppressor that negatively regulates the PI3K/AKT pathway. AB also disrupted the phosphorylation of AKT-controlled eukaryotic translation initiation factor, 4E-BP1, and GSK-3β, both of which are aberrantly regulated in human cancer. The AB-dependent downregulation of NF-κB was corroborated by the inhibition of TNFα-induced NF-κB activity as monitored in a luciferase reporter. The NF-κB inhibitory activity of AB was 3-fold more potent than that of the standard inhibitor, N-p-Tosyl-l-phenylalanine chloromethyl ketone. In addition to reducing the pro-survival effects of NF-кB, the inhibition of AKT phosphorylation by AB may also lead to FOXO1-mediated growth arrest and apoptosis. AB upregulated the expression of phospho-MKK4 and phospho-p38, and downregulated the expression of phospho-MEK1/2 and phospho-ERK1/2 indicating opposing effects on the two important oncogenic signaling cascades that are aberrantly activated in many cancers. AB disrupted both the AKT and ERK1/2 signaling pathways leading to apoptosis in ER+ MCF-7 cells through mitochondria-associated mechanisms coupled with the potent inhibition of NF-кB activation. The clinical limitations of multi-agent combination therapy that targets multiple pathways in cancer may potentially be circumvented by using a single molecule, such as AB, that inhibits both AKT and ERK1/2 signaling. Our preliminary study suggested that the THAQ pharmacophore, with its disrupted conjugated ring system and relative redox inactivity, may possess greater mechanistic advantage against ER+ breast cancer when compared to the fully conjugated ring systems of the anthraquinone that possess intrinsic redox activity and DNA interacting ability. This study supports the continued investigation of THAQs as lead molecules in anticancer drug discovery and development.

Conjugation of triphenylantimony(V) with carvacrol against human breast cancer cells.

The organoantimony derivative of formula trans-O,O-[Ph3SbV(Carv)2] (TPAC) (CarvH = carvacrol) is obtained by the oxidation of triphenylstibine (Ph3SbIII) with hydrogen peroxide in the presence of carvacrol (CarvH). Physical methods such as X-ray Fluorescence (XRF) spectroscopy, single crystal and powder X-ray diffraction analysis (XRD and PXRD), Attenuated Total Reflection Fourier Transform Infra-red (ATR-FTIR) spectroscopy, Thermogravimetric Differential Thermal Analysis (TG-DTA) and Differential Scanning Calorimetry (DTG/DSC), confirm the retention of the formula of TPAC throughout the sample mass in solid state, while UV-Vis spectroscopy in the solution. TPAC is the first example of carvacrol (the main ingredient of oregano) covalently bonded to any metal ion. Only the trans-O,O-[Ph3Sb(Carv)2] isomer was isolated suggesting stereo-selectivity of the preparation route. TPAC inhibits in vitro both human breast adenocarcinoma cell lines: MCF-7 (positive to hormones receptor (HR +)), MDA-MB-231 (negative to hormones receptor (HR-)) stronger than normal human fetal lung fibroblast cells (MRC-5). The MCF-7 cells morphology, DNA fragmentation, Acridine Orange/Ethidium Bromide (AO/EB) Staining, cell cycle arrest and mitochondrial membrane permeabilization tests suggest an apoptotic pathway for cell death, especially, through the mitochondrion damage. The binding type of TPAC toward the calf thymus CT-DNA was initially deduced ex vivo from the differentiation of the DNA solution viscosity. Fluorescence spectroscopy confirms the interaction mode suggested. Spectroscopic evidence (FTIR, UV-Vis) suggest that glutathione (GSH) (a tripeptide over-expressed in tumor cells) induces conversion of non-active pentavalent antimony, which is contained in TPAC, to active trivalent one, providing a new strategy for the development of targeted chemotherapeutics.

Gold(III) heteroleptic complexes with SNS-thiosemicarbazonate ligands as cytotoxic agents: Experimental and computational insights into the mechanism of action

New gold(III) heteroleptic complexes of general formula [AuX(dmtsc)], with (dmtsc)2– = (diethylaminothiocarbonyl)benzimidoyl-morpholinyl-thiosemicarbazonate and X = xant– (ethyl xanthate) or damp– (dimethyl-1-phenylmethanamine), were synthesized and compared to the chlorido precursor [AuCl(dmtsc)]. The characterization of the new complexes included FTIR, elemental analysis, molar conductivity, UV–Vis, 1H and 13C NMR spectroscopies and ESI(+)-MS. In addition, the xanthate derivative was analyzed by single-crystal X-ray diffraction. In vitro assays against three tumor cell lines (B16-F10, HCT-8 and MDA-MB-231) showed that the gold(III) complexes display remarkable antiproliferative effects on human breast adenocarcinoma cell line with influence of the co-ligands. The cytotoxicity on VERO cells was also investigated revealing that the organometallic complex [Au(damp)(dmtsc)] was the most selective compound for MDA-MB-231, although not the most active. Attempting to comprehend their behavior in biological medium, studies involving the interactions with possible biological targets were performed by experimental methods and theoretical docking simulations. Their results indicated that HSA might be a probable carrier of the compounds in the biological medium, whereas DNA is not supposed to be their main target. On the other hand, all compounds totally inhibited thioredoxin reductase enzyme (TrxR) at the concentration of 50 μM and formed significant molecular interactions, suggesting that it might be one of the molecular targets of these gold(III) complexes.

Mixed ligand complexes of nickel (ii): Synthesis and bio medicinal studies

Mixed ligand nickel (II), complexes of 2, 2 bipridyle and thioamides of 2-aminopyridine, 2-aminoadinine, 2-aminoguanine and 2-aminocytocine were prepared. The success of synthesis was confirmed through physical and spectral characterization on the basis of IR and NMR spectroscopy, antimicrobial and antitumour studies. The synthesized compounds were found to be active against the tested three bacterial strains (Pseudomanas auruginosa, Klebseila pneumonia and Staphylococcus aureus), two fungal strains (Aspergillus flavus and Aspergillus nigar) and antitumour activity against MCF-7 (Human breast adenocarcinoma) cell line.

DNA binding and cleavage, BRCA1 gene interaction, antiglycation and anticancer studies of transition metal complexes of sulfonamides.

A series of 4-((4-methylphenylsulfonamido)methyl)cyclohexanecarboxylic acid (NaMSCCA) transition metal complexes [Cu(II), Zn(II), Ni(II), Mn(II), and Co(II)] have been synthesized by precipitation method. The characterization was done by physical techniques, FT-IR spectroscopy, mass spectrometry, and NMR spectroscopy. The molecular structures of nickel (II) AZ-3 and cobalt (II) AZ-5 complexes were determined by the X-ray diffraction technique and found to crystallize in the triclinic space group P-1. The coordination geometry around the central nickel (AZ-3) and cobalt (AZ-5) atoms was square planar bipyramidal. Molecular docking was performed with duplex DNA of sequence d(CGCGAATTCGCG)2 DNA to determine the probable binding mode of compounds. Then these synthesized compounds were used to perform DNA cleavage activity through the agarose gel electrophoresis method. Among the compounds, compounds AZ-1 and AZ-2 exhibited good nuclease activity. The DNA sequence of breast-cancer suppressor gene 1 (BRCA1) was amplified through PCR and interaction studies of compounds AZ-1 and AZ-2 were performed through gel electrophoresis and fluorescence emission spectroscopy. The expression analysis of the BRCA1 gene was also performed to quantify the expression relative fold change (2^-(∆∆CT)) after treatment with compounds. All synthesized compounds were evaluated for their antioxidant and antiglycation activities and AZ-2 exhibited excellent results. The molecular docking study of these compounds was performed against the protein structure of advanced glycation end products to support the experimental results. Anticancer activity of compounds was performed through MTT assay. Copper and zinc complexes depicted the highest anticancer activity against human breast adenocarcinoma (MCF7) and human corneal epithelial cell (HCEC) cell lines.

The photodynamic reaction with IR-775 cyanine combined with 2-methoxyestradiol in ovarian (SKOV-3) and human breast adenocarcinoma (MDA MB-231) cell lines

BackgroundPhotodynamic therapy (PDT) is known anticancer approach used mainly for topical skin cancer. However, it could serve as an excellent alternative to traditional anticancer therapies, such as chemotherapy or radiotherapy. AimsThe study aimed to assess the effect of PDT, where the combination of cyanine with 2-methoxyestradiol (2-Me) was used on mammary and ovary adenocarcinoma human cell lines. Materials and methodsThe cyanine IR-775 was used as the photosensitizer. Two human malignant adenocarcinoma cell lines – ovary and mammary adenocarcinoma (MDA MB-231 and SKOV-3) were investigated in photodynamic reaction (PDR), with the enhancement of 2-Me. PDR efficiency was evaluated by the MTT test. Photosensitizer intracellular distribution was assessed by fluorescent microscopy. Additionally, apoptotic and oxidative stress markers were investigated by immunocytochemistry staining. Results and conclusionsIt was observed that PDR enhanced by 2-Me is effective against two common but different types of cancer. The treatment decreased cells’ viability by around 70%. Immunocytochemical staining of SOD2 and caspase-12 indicated apoptosis and oxidative stress induction in tested cell lines. The results suggest that the therapy could be involved in further oncological applications.

Anticancer and antimicrobial activity of biosynthesized Red Sea marine algal silver nanoparticles

Biosynthesis of silver nanoparticles (AgNPs) is emerging as a simple and eco-friendly alternative to conventional chemical synthesis methods. The role of AgNPs is expanding as antimicrobial and anticancer agents, sensors, nanoelectronic devices, and imaging contrast agents. In this study, biogenic AgNPs were synthesized using extracts of different marine algae species, including Ulva rigida (green alga), Cystoseira myrica (brown alga), and Gracilaria foliifera (red alga), as reducing and capping agents. The Physiochemical properties, cytotoxicity, anticancer and antimicrobial activities of the biosynthesized AgNPs were assessed. Surface plasmonic bands of the biosynthesized AgNPs capped with U. rigida, C. myrica, and G. foliifera extracts were visually observed to determine a colour change, and their peaks were observed at 424 nm, 409 nm, and 415 nm, respectively, by UV–Vis spectroscopy; transmission electron microscopy (TEM) indicated an almost spherical shape of AgNPs with nanoscale sizes of 12 nm, 17 nm, and 24 nm, respectively. Fourier transform-infrared (FTIR) spectroscopy analysis suggested that different molecules attached to AgNPs through OH, C=O, and amide groups. The major constituents of the aqueous algal extracts included, terpenoids, polyphenols, sulfonates, polysaccharides, fatty acids, chlorophylls, amide proteins, flavonoids, carotenoids, aliphatic fluoro compounds, volatile compounds, alkalines, pyruvic acid and agar groups. The cytotoxicity and anticancer activities of the biosynthesized AgNPs were assessed using Artemia salina nauplii, normal skin cell lines (HFb-4), and breast cancer cell lines (MCF-7 cell line). The lethality was found to be directly proportional to the AgNP concentration. The IC50 values of C. myrica and G. foliifera AgNPs against A. saline nauplii were 5 and 10 μg ml−1 after 4 h and 16 h, respectively, whereas U. rigida AgNPs did not exhibit cytotoxic effects. Anticancer activity of the biosynthesized AgNPs was dose dependent. The IC50 values of the biosynthesized AgNPs were 13, 13, and 43 µg ml−1 for U. rigida, C. myrica, and G. foliifera, respectively. U. rigida AgNPs particularly exhibited potent anticancer activity (92.62%) against a human breast adenocarcinoma cell line (MCF-7) with high selectivity compared the normal cells (IC50 = 13 µg/ml, SI = 3.2), followed by C. myrica AgNPs (IC50 = 13 µg/ml, SI = 3.07). Furthermore, the biosynthesized AgNPs exhibited strong antifungal activity against dermatophyte pathogenic moulds and mild antibacterial activity against the food borne pathogen bacteria. The highest antimicrobial activity was recorded for the U. rigida AgNPs, followed by those capped with C. myrica and G. foliifera extracts, respectively. AgNPs capped with the U. rigida extract exhibited the highest antimicrobial activity against Trichophyton mantigrophytes (40 mm), followed by Trichosporon cataneum (30 mm) and E. coli (19 mm), with minimal lethal concentration of 32 and 64 μg ml−1 respectively. The study finally revealed that extracts of marine algal species, particularly U. rigida extracts, could be effectively used as reducing agents for the green synthesis of AgNPs. These AgNPs are considered efficient alternative antidermatophytes for skin infections and anticancer agents against the MCF-7 cell line.

Antiproliferative activity and molecular docking studies of new 4-oxothiazolidin-5-ylidene acetate derivatives containing guanylhydrazone moiety

A new series of 4-oxothiazolidin-5-ylidene acetates (1–16) containing guanylhydrazone moiety were designed and synthesized by using dimethyl acetylenedicarboxylate (DMAD) as a Michael acceptor. The structure of synthesized compounds was characterized by various spectral techniques including FTIR, 1H NMR, 13C NMR and elemental analysis. Synthesized compounds were evaluated for their antiproliferative activity against two human cancer cell lines, A549 (human lung carcinoma cell line) and MDA-MB-231 (human breast adenocarcinoma cell line). Some of these compounds exhibit good antiproliferative activity in both cell lines. For example, compounds 1, 4, 9, 10, 12 and 15. Particularly, compounds 1, 9 and 10 showed the most potent activity against MDA-MB-231 cells with IC50 10.01, 7.72 and 9.61 µM respectively which is comparable to that of standard drug cisplatin and ploxal-S. Additionally, compounds that exhibited good activity were further investigated for their cytotoxicity against human healthy cell line (Wl-38). It was deduced from the MTT results that these compounds (1, 4, 9, 10 and 12), which have toxic effects on cancer cells, showed selectivity on healthy cells. Furthermore, molecular docking studies reviewed the interaction between the most active compound 9 to Caspase 9 protein of breast cancer and human lung cancer cells protein.

ROS‐responsive thioether‐containing hyperbranched polymer micelles for light‐triggered drug release

AbstractAs a kind of promising drug carriers, smart polymers have attracted much attention due to the effective and controlled drug release in target cells. Herein, a reactive oxygen species (ROS)‐responsive thioether‐containing amphiphilic hyperbranched polymer prepared from MTPA and TMPTGE (HBPMT) is synthesized from 3‐(methylthio)propylamine (MTPA) and trimethylolpropane triglycidyl ether (TMPTGE) by the amine‐epoxy click reaction via A2 + B3 one‐pot approach. Benefiting from its inherent amphiphilic nature, HBPMT can self‐assemble into stable micelles in water. Triggered by H2O2, these micelles can be dissociated rapidly because hydrophobic thioether segments in their cores are oxidized into hydrophilic sulfoxide or sulfone groups. Additionally, the ROS produced by photosensitizer under light irradiation can also play the same role of H2O2. Such HBPMT micelles can be utilized to encapsulate anticancer drug paclitaxel (PTX) and photosensitizer chlorin e6 (Ce6) simultaneously for drug delivery and control release. The methyl thiazolyl tetrazolium assay toward MCF‐7 tumor cells (a human breast adenocarcinoma cell line) indicates that these micelles encapsulated with PTX and Ce6 exhibit a significant combinational efficacy of cell proliferation inhibition, which means the promising potential for synergistic chemo‐photodynamic cancer therapy. Such a novel nanocarrier based on amphiphilic to hydrophilic transition would provide a candidate for controlled drug release and cancer combination therapy.

Antitumorigenic Effect of Tramadol and Synergistic Effect With Doxorubicin in Human Breast Cancer Cells.

BackgroundBreast cancer in women is one of the leading causes of cancer mortality worldwide, and curative therapy is the main focus of clinical treatment. Anesthetic-analgesic techniques might alter stress responses and immunity and thereby influence outcomes in cancer patients. This study investigated the effect of tramadol on breast cancer progression and metastasis.MethodsThe effects of tramadol on two different subtypes of human breast adenocarcinoma cell lines, MDA-MB-231 and MCF-7, were studied with regard to cell growth, migration, colony formation and invasion and normoxic or hypoxic microenvironment for the expression of hypoxia-inducible factor-1α, reactive oxygen species, epithelial-mesenchymal transition related and cyclin-related proteins. The co-administration of tramadol and doxorubicin was studied to determine whether the effective doxorubicin dose might be reduced in combination with tramadol.ResultsThe results showed that tramadol inhibited cell growth at concentrations more than 0.5 and more than 1.0 mg/mL in MDA-MB-231 and MCF-7 cells, respectively. Additionally, cell migration, colony formation and invasion were inhibited in a dose-dependent manner by tramadol in both cell lines. The combination of tramadol and doxorubicin induced synergistic effects in MDA-MD-231 cells and, with specific dosage combinations in MCF-7 cells.ConclusionsTramadol may regulate epithelial-mesenchymal transition and possess cytotoxic effects in breast cancer cells. Tramadol inhibits the progression of breast cancer cells and might be a candidate for combination therapy, especially for triple-negative breast cancer, and is a promising treatment strategy for breast cancer.

Monomeric octahedral bismuth(III) benzaldehyde-N1-alkyl thiosemicarbazones: Synthesis, characterization and biological properties

Due to their chemical and biological properties, the interest in thiosemicarbazones and their metal complexes is increasing day by day. In this study, the effect of the substituents at the N1 atoms of the thiosemicarbazones and the effect of halogen atoms on the type and biological properties of bismuth(III) complexes is investigated. The reactions of bismuth(III) halide with a series of benzaldehyde-N1-alkyl-thiosemicarbazones in 1:3 M ratio yield bismuth(III) halide complexes: {BiBr3(η1-S-Hbztsc)3} (1), {BiCl3(η1-S-Hbzmtsc)3} (2), {BiBr3(η1-S-Hbzmtsc)3} (3), {[BiCl3(η1-S-Hbzetsc)3].CH3OH} (4) and {BiBr3(η1-S-Hbzetsc)3} (5). Complexes 1–5 were characterized by a number of different spectroscopic methods. The crystal structures of complexes 1–5 and the free ligand benzaldehyde-N-methyl-thiosemicarbazone were determined by X-ray diffraction. Complexes 1–5 were tested for their in vitro cytotoxic activity against human breast adenocarcinoma (MCF-7) cell line. Complexes 1–5 showed low cytotoxic activity. The antibacterial activities of 1–5 and their free ligands against four strains bacteria of Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli have been examined. The results indicated that bismuth(III) complexes 1–5 are most active against E. coli and, among them, complex 4 exhibits the highest activity. Lipoxygenase (LOX) inhibitory activity of the bismuth(III) halide complexes 1–5 and the free ligands has been detected experimentally. The IC50 values indicate that bismuth(III) halide complexes 1–5 have a higher enzyme inhibition potential than free ligands and cisplatin.

Anticancer and Antimicrobial Activity of Red Sea Seaweeds Extracts-Mediated Gold Nanoparticles

Biosynthesis of gold nanoparticles (AuNPs) is emerging as a better alternative to traditional chemical-based techniques. During this study, extracts of different marine algae species Ulva rigida (green algae), Cystoseira myrica (brown Algae), and Gracilaria foliifera (red Algae) were utilized as reducing and capping agents to synthesize AuNPs. AuNPs capped by U. rigida, C. myrica, and G. foliifera were confirmed by the appearance of surface plasmonic bands at 528, 540, and 543 nm, respectively. Transmission electron microscopy revealed mostly spherical shapes of AuNPs having a size of about 9 nm, 11 nm, and 13 nm for C. myrica, and G. foliifera extracts, respectively. Fourier transform-infrared spectroscopy (FTIR) illustrated the major chemical constituents of U. rigida, C. myrica, and G. foliifera. LC50 values of the biosynthesized AuNPs against Artemia salina nauplii were calculated at a range of concentrations (5-188 μg ml−1) after 16 to 24h. AuNPs concentration-dependent lethality was noted and U. rigida extracts-mediated AuNPs presented the lowest cytotoxicity. The biosynthesized AuNPs exhibited significant anticancer activity (86.83%) against MCF-7 cell lines (human breast adenocarcinoma cell lines) at 188 µg/ml concentration. G. foliifera demonstrated the highest anticancer value (92.13%) followed by C. myrica (89.82%), and U. rigida (86.83%), respectively. The AuNPs synthesized by different algal extracts showed variable antimicrobial activity against the tested pathogenic microorganisms. AuNPs of U. rigida extracts showed significant antimicrobial activity against dermatophytic fungi Trichosporon cataneum (30 mm) followed by Trichophyton mantigrophytes (25 mm). Furthermore, it also exhibited mild activity against Escherichia coli (17 mm), Cryptococcus neoformans (15 mm), Candida albicans (13 mm), and Staphylococcus aureus (11mm), respectively whereas no effects were observed against Bacillus cereus. To conclude, AuNPs can be effectively synthesized by marine algal species, and particularly U. rigida extracts could be effective reducing agents for the green AuNPs synthesis. These AuNPs could potentially serve as efficient alternative anticancer agents against human breast adenocarcinoma and anti-dermatophytes associated with skin infections.