Human Breast Cancer Epithelial Cells Research Articles

Preliminary study on cytotoxicity of selegiline on different cancer cell lines: exploration of the induction of ROS-independent apoptosis in breast cancer cells.

The concept of drug repurposing is now widely utilized by biomedical scientists for drug discovery. An example of this is the use of selegiline (SEL), a monoamine oxidase inhibitor that was initially used for the management of depression but is now being considered for another purpose. This study compares the cytotoxic effects of SEL on different cancer cells. Further, the study explores the molecular mechanism of cell death, validating the possibility of its repurposing for cancer. Preliminary analysis of network pharmacological data was conducted in silico, followed by in vitro cytotoxicity tests on PC12, G361, MDA-MB231, MCF7, THP-1, and Hela cells under normoxic and hypoxic conditions, using the MTT assay. The mechanism of cell death was then confirmed by performing DAPI and FITC-conjugated Annexin V and Propidium Iodide (PI) staining assays. Additionally, ROS levels and PKC phosphorylation were also evaluated. In silico analysis has revealed that SEL is associated with ten genes linked to different cancer types. Specifically, SEL was most cytotoxic to neuronal pheochromocytoma, triple-negative human epithelial breast cancer cells, and ER+ and PR+ breast cancer cells. Furthermore, it was observed that this cell death occurred through ROS-independent apoptosis pathways. In addition, SEL was found to inhibit the phosphorylation of PKC, which may contribute to cell death. SEL induces apoptosis in breast cancer cells independently of reactive oxygen species and inhibits the phosphorylation of protein kinase C, which merits further exploration.

Development of cancer-targeted nano gold functionalized ruthenium(III)-doxorubicin complex: Synthesis, characterization and evaluation of DNA cleavage, anticancer and bioimaging activity

Metal-based drugs have attracted greater attention for cancer diseases because of biological relevance. However, some drawbacks are present in the metal complexes such as low stability and low bioavailability. Nanomaterials functionalized metal complexes can protect the stability and enhanced the bioavailability. In the present study, Nano gold functionalized ruthenium(III) complex from doxorubicin have been synthesized from ruthenium(III) complex and characterized using various spectrochemical techniques such as IR, UV, and NMR. In the metal complex, Doxorubicin (DOX) acts as a monobasic bidentate ligand and is coordinated through the carbonyl oxygen and phenolate oxygen of the anthracene ring. Based on spectral evidences, the complex [Ru(DOX)(PPh3)2Cl2] has an octahedral geometry. The Nano Au-Ru(III) DOX is analysed for their size, and morphology using XRD, SEM and HRTEM. X-ray diffraction pattern revealed that the complex has nanocrystalline in nature. The Nano Au-Ru(III) DOX is spherical shape and particle size is less than 15 nm. The DNA cleavage activity of [Ru(DOX)(PPh3)2Cl2] and Nano Au-Ru(III) DOX has been evaluated using pUC18 plasmid DNA and the results showed significant cleavage. The [Ru(DOX)(PPh3)2Cl2] and Nano Au-Ru(III) DOX have been tested against human breast cancer (MCF-7) and leukemia cancer cell lines (K-562) in vitro for its antitumor effects. The tumour activity of the Nano Au-Ru(III) DOX showed more promising activity than the [Ru(DOX)(PPh3)2Cl2]. The cell imaging of the Nano Au-Ru(III) DOX was examined against epithelial human breast cancer cell line (MDA-MB-231) using fluorescent microscopy. The fluorescence images showed high scattering light in tumour tissue at 100 µg/mL Hence, Nano Au-Ru(III) DOX can serve as a promising drug for cancer therapy and cellular imaging.

Facile Green Synthesis of Iron Oxide Nanoparticles and Their Impact on Cytotoxicity, Antioxidative Properties and Bactericidal Activity.

Bioreductive processes are quite potent, effective and affordable for the synthesis of green nanoparticles (NPs), as compared to the physical and chemical methods. The present study aimed to evaluate the bactericidal, antioxidative and anticancer activity of turmeric rhizome-iron oxide nanoparticles (FeONPs) derived from the turmeric rhizome (Curcuma amada) using ferric chloride as a precursor. With focusing on the manufacture of FeONPs via green approach, we characterized the NPs using FTIR, FT-Vis, DLS, and UV-Vis spectroscopy. The produced particles were tested for antibacterial, antioxidant, and anticancer properties. The synthesized NPs were also examined using the MDA-MB-231 human epithelial breast cancer cell line and NCI-60 cancer cell lines. The antioxidant activity of TR-FeONPs was concentration-dependent. The scavenging activity of TR-FeONPs was 76.09% at a concentration of 140 µg/ml. Using different concentrations of TR-FeONPs in the MTT assay against the MDA-MB-231 cell line indicated a reduction of less than 50% in cell viability at 125 µg/ml. Moreover, TR-FeONPs exhibited an effective bactericidal property. The gTR-FeONPs synthesized bioreductively were found to be effective in renal cancer, UO-31 cell line, with GI50 value of 66.64%. Our study showcases a sustainable method based on green chemistry principles to produce FeONPs utilizing turmeric rhizome. We anticipate that the FeONPs produced through this biosynthesis process could serve as a promising drug delivery system in cancer treatment and as an effective antimicrobial agent against various diseases.

Abstract A089: Role of Vardhamana Pippali Rasayana (VPR) in human breast cancer cells

Abstract Serious concerns include delayed diagnosis and adverse side-effects of conventional treatment leading to residual morbidity in Breast cancer (BC) globally. Traditional Indian medicines/herbs via combination of conventional cancer are gaining increasing acceptance worldwide, playing a pivotal role as proven by their efficacy evaluation studies. Many plants are known to reduce the cell proliferation and tumor development after their treatment. Vardhamana Pippali Rasayana (VPR), an Ayurvedic herbal preparation of pippali (Piper longum) in gradually increasing and tapering dose is used to treat many cancers without any adverse side-effects. However, its anti-cancer role in breast cancer is not known yet. The present study has explored the cytotoxic and apoptotic effects of VPR in triplicates on human breast cancer (MCF7) and normal breast epithelial (MCF10A) cell lines at different concentrations after extracting piperine in aqueous and hydro-alcoholic soxhlet extract (0.25 to 50 μg/μl). The cytotoxic activity was carried out by MTT assay and results showed that a low IC50 was observed at 3.75 μg/μl of VPR against MCF-7 as compared with normal breast epithelial cells. Detection of apoptotic cells using suitable Annexin V was done and there was a time-dependent increase in percentage of annexin V positive cells upon treatment. The above results indicate that VPR may have a strong anti-cancerous potential. But other functional assays are warranted to validate the efficacy of the drug against breast cancer which are under progress in our laboratory. Citation Format: Dr.Richa Tripathi, Shivam Singh, Subhash Gupta, VG Huddar, Tanuja M Nesari, Ashok Sharma. Role of Vardhamana Pippali Rasayana (VPR) in human breast cancer cells [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A089.

Metabolomic profiling of Medicago sativa-derived fungal endophytes and evaluation of their biological activities.

This study aimed to discover the potential of Medicago sativa-derived fungal endophytes as a prospective source of bioactive metabolites. In the present study, three different strains of fungal endophyte Aspergillus terreus were isolated from leaves L, roots T and stems St of Medicago sativa to explore their biological and chemical diversity. These isolated fungi were exposed to different fermentation conditions by adding various chemical elicitors to their solid fermentation media. According to LC-HRESIMS-based metabolomics and multivariate analysis, each chemical treatment had a different effect on the chemical profiles of the fungi. Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) proposed several compounds with anticancer action against MCF-7 (a human breast cancer cell line) and MDA-MB-231 (a human epithelial breast cancer cell line).

Assessments of anti-breast cancer activity and profiling of active compounds using LC-MS/MS from the Indonesian Agelas nakamurai

Breast cancer is now one of the leading causes of death in women worldwide. Finding a cure is, therefore, critical for women’s health. Marine sponge-derived drugs have gained interest in breast cancer treatment. The development of marine natural products into cancer therapy includes several stages. It starts with the screening using the cytotoxic test method, a preclinical trial using the animal mode, and clinical trial phases I and II. In this study, we focus on the basic cytotoxic test to find the new source of anti-breast cancer compounds derived from Agelas nakamurai to know the potential for further investigation to become lead compounds. However, the anti-breast cancer potential of the Indonesian marine sponge A. nakamurai has never been studied. This study aimed to evaluate the anti-breast cancer potential of extract and fraction of A. nakamurai against epithelial human breast cancer cells (MDA-MB-231 and MCF-7 cells line) and to preliminary profile the known active compounds. The maceration using methanol was used for extraction and followed by partitioning with varied solvents [ethyl acetate (EtOAc), butanol, and water]. Fractionation was done using normal phase open column chromatography, and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) was used for analyzing compounds. MDA-MB-231, MCF-7, and HEK-293 cell lines were used for biological activities. The chromatographic separation of the EtOAc fraction led to the F7 subfraction which strongly inhibits proliferation against the MDA-MD-231 (IC50: 10.677 μg/mL), MCF-7 (IC50: 15.154 μg/mL), and HEK-293 cells line. The LC-MS/MS data of active fraction F7 contained gelatin-D and ageloxime-D. This study reported that fraction 7 of A. nakamurai showed strong activity against MDA-MB-231, MCF-7, and HEK-293 cell lines. Further analysis will be carried out to know the mechanisms of action of active compounds.

Interfacial Organization and Forces Arising from Epithelial-Cancerous Monolayer Interactions.

The interfacial interactions between epithelia and cancer cells have profound relevance for tumor development and metastasis. Through monolayer confrontation of MCF10A (nontumorigenic human breast epithelial cells) and MDA-MB-231 (human epithelial breast cancer cells) cells, we investigate the epithelial-cancerous interfacial interactions at the tissue level. We show that the monolayer interaction leads to competitive interfacial morphodynamics and drives an intricate spatial organization of MCF10A cells into multicellular finger-like structures, which further branch into multiple subfinger-like structures. These hierarchical interfacial structures penetrate the cancer monolayer and can spontaneously segregate or even envelop cancer cell clusters, consistent with our theoretical prediction. By tracking the substrate displacements via embedded fluorescent nanobeads and implementing nanomechanical modeling that combines atomic force microscopy and finite element simulations, we computed mechanical force patterns, including traction forces and monolayer stresses, caused by the monolayer interaction. It is found that the heterogeneous mechanical forces accumulated in the monolayers are able to squeeze cancer cells, leading to three-dimensional interfacial bulges or cell extrusion, initiating the p53 apoptosis signaling pathways of cancer cells. We reveal that intercellular E-cadherin and P-cadherin of epithelial cells differentially regulate the interfacial organization including migration speed, directionality, spatial correlation, F-actin alignment, and subcellular protrusions of MCF10A cells; whereas E-cadherin governs interfacial geometry that is relevant to force localization and cancer cell extrusion, P-cadherin maintains interfacial integrity that enables long-range force transmission. Our findings suggest that the collaborative molecular and mechanical behaviors are crucial for preventing epithelial tissues from undergoing tumor invasion.

A combination of a cell penetrating peptide and a protein translation inhibitor kills metastatic breast cancer cells

Cell Penetrating Peptides (CPPs) are promising anticancer and antimicrobial drugs. We recently reported that a peptide derived from the human mitochondrial/ER membrane-anchored NEET protein, Nutrient Autophagy Factor 1 (NAF-1; NAF-144-67), selectively permeates and kills human metastatic epithelial breast cancer cells (MDA-MB-231), but not control epithelial cells. As cancer cells alter their phenotype during growth and metastasis, we tested whether NAF-144–67 would also be efficient in killing other human epithelial breast cancer cells that may have a different phenotype. Here we report that NAF-144–67 is efficient in killing BT-549, Hs 578T, MDA-MB-436, and MDA-MB-453 breast cancer cells, but that MDA-MB-157 cells are resistant to it. Upon closer examination, we found that MDA-MB-157 cells display a high content of intracellular vesicles and cellular protrusions, compared to MDA-MB-231 cells, that could protect them from NAF-144–67. Inhibiting the formation of intracellular vesicles and dynamics of cellular protrusions of MDA-MB-157 cells, using a protein translation inhibitor (the antibiotic Cycloheximide), rendered these cells highly susceptible to NAF-144–67, suggesting that under certain conditions, the killing effect of CPPs could be augmented when they are applied in combination with an antibiotic or chemotherapy agent. These findings could prove important for the treatment of metastatic cancers with CPPs and/or treatment combinations that include CPPs.

Expression of NORAD correlates with breast cancer aggressiveness and protects breast cancer cells from chemotherapy

The recently discovered human lncRNA NORAD is induced after DNA damage in a p53-dependent manner. It plays a critical role in the maintenance of genomic stability through interaction with Pumilio proteins, limiting the repression of their target mRNAs. Therefore, NORAD inactivation causes chromosomal instability and aneuploidy, which contributes to the accumulation of genetic abnormalities and tumorigenesis. NORAD has been detected in several types of cancer, including breast cancer, which is the most frequently diagnosed and the second-leading cause of cancer death in women. In the present study, we confirmed upregulated NORAD expression levels in a set of human epithelial breast cancer cell lines (MDA-MB-231, MDA-MB-436, and MDA-MB-468), which belong to the most aggressive subtypes (triple-negative breast cancer). These results are in line with previous data showing that high NORAD expression levels in basal-like tumors were associated with poor prognosis. Here, we demonstrate that NORAD downregulation sensitizes triple-negative breast cancer cells to chemotherapy, through a potential accumulation of genomic aberrations and an impaired capacity to signal DNA damage. These results show that NORAD may represent an unexploited neoadjuvant therapeutic target for chemotherapy-unresponsive breast cancer.

One–pot synthesis of gold nanoparticles using Pandanus amaryllifolius leaf extract and their antibacterial, antioxidant, anticancer, and ecotoxicity assessment

This work demonstrated a one–pot synthesis of gold nanoparticles (Au NPs) using Pandanus amaryllifolius leaf extract as well as their biological activity and biocompatibility impacts. The synthesized Au NPs were characterized by UV–vis, FT–IR, XRD, XPS, DLS, ZP, SEM, element mapping, EDX, and TEM analysis. The Au NPs tested against Gram–positive and negative bacteria of Staphylococcus aureus and Escherichia coli. The antioxidant capacity of Au NPs showed a moderate effect. Different concentrations of Au NPs were tested on the MDA–MB–231 epithelial human breast cancer cell line, showing that IC50 value at 118.26 μg/mL. Au NPs treated Artemia salina nauplii did not promote any mortality. By contrast, microphotographic analysis of the Au NPs found in the aggregated form inside the guts region. The 100% Au NPs treated Allium cepa root tip cell showed a mitotic index of 77.63 ± 0.42. This investigation demonstrates that Au NPs have better antioxidant and anticancer activities. In addition, the A. salina nauplii emphasized nontoxicity with biocompatibility. The Au NPs treatments showed a dose–depended response to enhance the mitotic cell divisions of A. cepa root tip cells without chromosomal aberration and no antibacterial efficiency of Au NPs against bacterial pathogens. Our study shows that this one–step synthesis is highly efficient. Near the future, synthesized Au NPs can be used for cancer therapeutic, food packaging, and cosmetic applications.

Apoptotic Induction in Human Cancer Cell Lines by Antimicrobial Compounds from Antarctic Streptomyces fildesensis (INACH3013)

The Antarctic Streptomyces fildesensis has been recognized for its production of antimicrobial compounds with interesting biological activities against foodborne bacteria and multi-resistant strains, but not for its potential antiproliferative activity and mechanisms involved. Two bioactive ethyl acetate extract (EAE) fractions were purified via thin-layer chromatography and High-Performance Liquid Chromatography (HPLC), showing that orange-colored compounds displayed antimicrobial activity against pathogenic bacteria even after shock thermal treatment. The UV–VIS features of the active compounds, the TLC assay with actinomycin-D pure standard, Fourier transform infrared (FTIR) spectra and the ANTISMASH analysis support the presence of actinomycin-like compounds. We demonstrated that S. fildesensis displays antiproliferative activity against human tumor cell lines, including human breast cancer (MCF-7), prostate cancer (PC-3), colon cancer (HT-29) and non-tumoral colon epithelial cells (CoN). The half-maximal effective concentrations (EC50) ranged from 3.98 µg/mL to 0.1 µg/mL. Our results reveal that actinomycin-like compounds of S. fildesensis induced apoptosis mediated by caspase activation, decreasing the mitochondrial membrane potential and altering the cell morphology in all tumoral and non-tumoral cell lines analyzed. These findings confirm the potential of the psychrotolerant Antarctic S. fildesensis species as a promising source for obtaining potential novel anticancer compounds.

Synthesis of Iron oxide Nanoparticle using Propolis from Northern Cyprus and Evaluation of its Antibacterial, Anticancer Potential on MDA-MB 231 cells

Research in nanotechnology has progressed in the last decades, and it is purposeful to explore the applications of biocompatible nanoparticles in general and their anticancer attribute specifically. This study is aimed at examining the cytotoxic effects of biocompatible Northern Cyprus propolis extract of iron oxide nanoparticles (PE-Fe2O3-NPs) on MDA-MB-231 epithelial human breast cancer cell line, in vitro. Propolis extract were used to obtain PE-Fe2O3-NPs and further characterized using several methods like ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, scanning electronic microscopy and X-ray diffraction analysis. The PE-Fe2O3-NPs has a distinctive Surface Plasmon Resonance band at 350 nm. The prepared PE-Fe2O3-NPs had a size of 108 nm by diameter with a zeta potential of +33.9 mV which indicates a good stability of the nanoparticles’ while the size of Fe2O3-NPs was 89.40 nm by diameter. Antibacterial result showed that Fe2O3-NPs has highest Minimum Inhibitory Concentration and Minimum Bactericidal Concentration as compared to PE-Fe2O3-NPs with different concentration of propolis extract as regards the tested microorganisms. This indicates that PE-Fe2O3-NPs possesses a more effective threat to eliminating pathogenic bacteria at lesser dosages, be it Gram-ve or Gram+ve. PE-Fe2O3-NPs effectively halted the spread of MDA-MB-231 cancer cell lines and thus, prove to be commendable for anticancer biomedical uses.

Cytotoxic Activity of Leaves Essential oils of Aeollanthus heliotropioides and Ocimum urticaefolium (Lamiaceae) from Cameroon on the Breast Cancer (MCF-7) and Epithelial (ARPE-19) Cells

Background: The aim of this work was to study the cytotoxicity of leaves essential oils and their identified constituents of Aeollanthus heliotropioides and Ocimum urticaefolium (Lamiaceae) from Cameroon. Materials and Methods: Leaves essential oils were obtained by hydrodistillation and were analysed by gas chromatography (GC) and GC/mass spectrometry (MS). The cytotoxic activity was evaluated in Human breast cancer (MCF-7) and normal epithelial (ARPE-19) cells line by MTT assay. Results: The essential oils of Aeollanthus heliotropioides and Ocimum urticaefolium leaves were found to most constitute by sesquiterpene components with 52.8% and 67.3% respectively than monoterpenes. The major constituents of the essential oil of Aeollanthus heliotropioides are linalool (43.4%), (E)-(Z)-farnesene (27.7%), (δ- Cadinol (13.0%), germacrene D (3.7%), α-caryophyllene (3.1%). Eugenol (26%), (Z)--ocimene(5.3%), α- caryophyllene (5%), germacrene D (4.4%), δ-muurolène (17%) , spathulenol (14.2%), δ-Cadinol (11.3%), (E)-Z-farnesol (5.4%) and 6E)-2Z-farnesol (3.6%) are the main major components of Ocimum urticaefolium essential oil. The cytoxicity of Aeollanthus heliotropioides and Ocimum urticaefolium oils indicate that the oils have a good cytotoxicity against breast cancer cells (MCF-7) growth with IC50 values of 0. 620μL/mL and 0.422 μL/mL. The highest selectivity was obtained with the essential oil Aeollanthus heliotropioides (1.72) which was more cytotoxic against MCF-7 than against normal cell line (ARPE-19) with IC50 values of 0.620 μL/mL and 1.07 μL/mL, respectively. Conclusion: This study suggests for the first time the ability of Aeollanthus heliotropioides and Ocimum urticaefolium essential oils to inhibit human tumor cell growth. They could be considered as a potent source of alternate lead compounds against breast cancer.

Frankincense oil-loaded nanoemulsion formulation of paclitaxel and erucin: A synergistic combination for ameliorating drug resistance in breast cancer: In vitro and in vivo study.

Nanoformulation-based combinational drug delivery systems are well known to overcome drug resistance in cancer management. Among them, nanoemulsions are well-known and thermodynamically stable drug delivery systems suitable for carrying hydrophobic drugs and phytoconstituents to tackle drug-resistant cancers. In the present study, we have investigated the effect of paclitaxel in combination with erucin (natural isothiocyanate isolated from the seeds of Eruca sativa) loaded in the frankincense oil-based nanoemulsion formulation. The choice of frankincense oil for the current study was based on reported research investigations stating its magnificient therapeutic potential against breast cancer. Optimized nanoemulsion of paclitaxel (PTX) and erucin (ER) combination (EPNE) provided sustained release and exhibited enhanced cytotoxicity towards human epithelial breast cancer cells (T-47D) as compared to individual ER and PTX. EPNE was further assessed for its antitumor activity in the 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer mice model. EPNE significantly decreased the levels of hepatic and renal parameters along with oxidative stress in breast cancer mice. Furthermore, EPNE also showed decreased levels of inflammatory cytokines TNF-α, IL-6. Histopathological examinations revealed restoration of the tumorous breast to normal tissues in EPNE-treated breast cancer mice. Therefore, EPNE can act as a viable lead and therapeutic option for drug-resistant breast cancer.

Formulation and Characterization of Raloxifene Nanostructured Lipid Carriers for Permeability and Uptake Enhancement Applications.

Raloxifene (RLX), a biopharmaceutical classification system (BCS) class II drug, is a selective estrogen receptor modulator (SERM) having an estrogenic effect on the bone and an antiestrogenic effect on the endometrium and breast. Low solubility, high permeability, high metabolism, and low bioavailability are the characteristics of raloxifene. Although 60% is absorbed orally, raloxifene shows extremely poor bioavailability (2%) owing to its low solubility and extensive (>90%) intestinal/hepatic first-pass metabolism. Hence, it becomes important to increase the solubility of raloxifene to enhance its bioavailability. In this study, raloxifene nanostructured lipid carriers (RNLCs) were prepared using the melt dispersion ultrasonication method. The prepared RNLCs were characterized, and the in vitro studies were carried out in the human epithelial breast cancer cell line (MCF-7). The RNLCs had a size of 114.8 ± 0.98 nm and a zeta potential of +9.21 ± 0.58 mV. Transmission electron microscopy (TEM) images showed particle size ranging from 65 to 120 nm. With an entrapment efficiency of 75.04% ± 2.75%, the RNLCs showed sustained release over 7 days compared with the raloxifene drug solution. The prepared RNLCs were successfully taken up by the MCF-7 cells in a time-dependent manner, and the RNLCs showed increased cell cytotoxicity compared with the raloxifene drug. Using the parallel artificial membrane permeability assay (PAMPA), the permeability rate for raloxifene solution was calculated to be 8 × 10-6 cm/s, and for the RNLCs, it was calculated to be 17.8 × 10-6 cm/s. Hence, from the permeability rate calculated, we could conclude that raloxifene, when formulated as nanostructured lipid carriers, showed increased permeability. Overall, the prepared RNLCs were found to be superior to the raloxifene drug as such.

Establishment of an orthotopic tumor model in the mammary gland of BALB/C nude mice using human breast cancer MCF-7 cells and their VDAC-deficient derivatives

Purpose to study the tumor-forming activity of wild-type MC F-7 cells carrying a full set of porins (VDAC 1, VDAC 2, VDAC 3), as well as their genetically modified cells, from which one of the isoforms was removed (MC F-7 VDAC 1 KO, MC F-7 VDAC 2 KO, MC F -7 VDAC 3 KO).Material and Methods. The study was aimed at establishing of an animal model of orthotopic tumors in the mammary gland of immunodeficient BAL B/c nude mice by implanting a suspension of human breast cancer cells (MC F-7) and derivatives of these cells generated by targeted knockout of one of the selected mitochondrial porin isoforms (VDAC 1, VDAC 2 or VDAC 3). Suspensions of either wild-type MC F-7 cell lines containing all three porin isoforms (VDAC 1, VDAC 2 and VDAC 3) or their VDAC -deficient derivatives (MC F-7 VDAC 1 KO, MC F-7 VDAC 2 KO and MC F-7 VDAC 3 KO) were injected into mammary fat pads of BAL B/c nude mice at a dose of 4x106 cells per injection. A pathomorphological analysis of the place of implantation of tumor cells, the tumor itself, as well as the organs of the abdominal and thoracic cavity was carried out.Results. The study shows the feasibility of successful creation of orthotopic tumors in the adipose tissue of immunodeficient BAL B/c nude mice with MC F-7 human breast cancer epithelial cells containing a complete set of mitochondrial porin isoforms and their VDAC -deficient derivatives. The tumor-forming activity of the implanted cells was shown to correlate with their cytotoxic effect on the internal organs of animals. Pathological analysis showed that all implanted cell cultures, such as MC F-7 WT, MC F-7 VDAC 2 KO and MC F-7 VDAC 3 KO, except for MC F-7 VDAC 1 KO cells, which did not form tumors, caused pathological changes in the lungs, liver and spleen, as well as the presence of other tumor-like lesions.Conclusion. The data obtained will be used to optimize the injection volume and cell number, as well as to refine the dynamics of tumor growth, suitable for studying the effect of anticancer drugs on tumors formed by human breast cancer cells (MC F-7) and its genetically modified VDAC -deficient derivatives.

A peptide-derived strategy for specifically targeting the mitochondria and ER of cancer cells: a new approach in fighting cancer.

An effective anti-cancer therapy should exclusively target cancer cells and trigger in them a broad spectrum of cell death pathways that will prevent avoidance. Here, we present a new approach in cancer therapy that specifically targets the mitochondria and ER of cancer cells. We developed a peptide derived from the flexible and transmembrane domains of the human protein NAF-1/CISD2. This peptide (NAF-144-67) specifically permeates through the plasma membranes of human epithelial breast cancer cells, abolishes their mitochondria and ER, and triggers cell death with characteristics of apoptosis, ferroptosis and necroptosis. In vivo analysis revealed that the peptide significantly decreases tumor growth in mice carrying xenograft human tumors. Computational simulations of cancer vs. normal cell membranes reveal that the specificity of the peptide to cancer cells is due to its selective recognition of their membrane composition. NAF-144-67 represents a promising anti-cancer lead compound that acts via a unique mechanism.

Assessment of cranberry bush on MCF-7 human breast cancer cells

This research aimed to study the effects of different doses Viburnum opulus L. (VO) powder extracts at different times on human breast cancer and breast epithelial cell lines. The cytotoxic effect evalueted by using MTT method and apoptosis induction annexin V-FITC/PI staining. Comet assay was used to detect the genotoxic effect by calculating the percentage of the tail length in the DNA of both cell groups. P1 class glutathione-S-transferase (GSTP1) expression level which hasprotective feature in drug resistance metabolism was studied by immunocytochemistry method and GSTP1 and total GSTA1 metabolic protein level spectrophotometer method. This study shows that DNA damage, intracellular cytotoxicity and apoptosis have increased due to the antioxidant properties of VO powder extract.GSTP1 activities by using ethacrynic acid as substrate were found statistically significant differences between all of the groups with oneway Annova test (** P <0.01).GSTP1 overexpressed in MCF-7 control cells and expression levels decreased in the MCF-7 groups that treatment with VO powder extract at different concentrations of 25, 50 and 100 µg/µL for 24, 48 and 72 h. This study provided the information that VO powder extract may be suitable for drug therapy efficacy at the molecular level.

Cytotoxic activity of organotin compounds containing non-steroidal anti-inflammatory drugs

Two series of organotin (IV) complexes based on diclofenac L1Na and aspirin L2H of formulae Me3SnL1 (1); Ph3SnL1 (2); Bu2Sn(L1)2 (3); R2Sn(L1)2 (4, R = 3,5-di-tert-butyl-4-hydroxyphenyl); Me3SnL2 (5); Me3Sn(2-hydroxybenzoate) (6) and Me2Sn(L2)2 (7) were synthesized and characterized by 1H, 13C, 119Sn NMR, IR, ESI-MS and elemental analysis. It was found by X-ray diffraction analysis of compound 1 that carboxyl group of diclofenac binds two tin atoms each being in the trigonal bipyramid geometry and having coordination number 5. Compounds 6 and 7 were found to be monomers in the solid state with tetrahedron and octahedron geometry around Sn center, respectively. Cytotoxicity in vitro of compounds 1–7 and initial ligands was evaluated on human colon cancer (HCT-116), human breast cancer (MCF-7) and adenocarcinomic human alveolar basal epithelial (A-549) cells. The IC50 values varied in 0.17–200 µM range for compounds 1–4 and in 3.3–200 µM range for compounds 5–7 depending on the substituents at Sn center and ligand structure. It was found that compound 2 possesses the maximal cytotoxic activity and significantly induces apoptosis of HCT-116 cells.

Improvement of cytotoxicity of mitoxantrone and daunorubicin by candidone, tephrosin, and bavachinin.

Flavonoids have been demonstrated to have the ability of sensitizing cancer cells to chemotherapy and inverse multidrug resistance via various mechanisms, such as modulating of pumps. The therapeutic effect of candidone, tephrosin, and bavachinin in treatment of cancer, particularly to overcome multidrug resistance (MDR) is largely unknown. The capacity of these agents in sensitization of MDR cells is investigated in the current work. We analyzed the impact of candidone, tephrosin, and bavachinin, as chemosensitizer on cell cytotoxicity, P-gp and ABCG2 mRNA expression level on two multidrug resistant cells, ABCG2 overexpressing human epithelial breast cancer cell line (MCF7/MX), and P-gp overexpressing human gastric adenocarcinoma cell line (EPG85.257RDB). The inhibitory concentration of 50% (IC50) of daunorubicin in EPG85.257RDB cells in combination with IC10 of Bavachinin, Tephrosin, and Candidone were 6159 ± 948, 4186 ± 665, 730 ± 258nM, and this data in MCF7/MX cell were 1773 ± 534, 7160 ± 405 and 3340 ± 622nM respectively. These three flavonoids dose-dependently decreased the viability of MCF7/MX and EPG85.257RDB and significantly (p < 0.05) decreased IC50 of daunorubicin and mitoxantrone except Tephrosin in MCF7/MX cells. Candidone and Bavachinin were the most potent chemosensitizer in EPG85.257RDB and MCF7/MX cells respectively. Flavonoids did not reduce mRNA expression of P-gp and ABCG2 after 72h treatment, except Candidone in EPG85.257RDB and Bavachinin in MCF7/MX cells. This effect is not time-dependent, and flavonoids have their own patterns that are cell-dependent. In general, tephrosin, candidone, and bavachinin had the potential of sensitizing MDR cells to mitoxantrone and daunorubicin.