Growth Of MCF-7 Cells Research Articles

Alkylamino Phenol Derivative Induces Apoptosis by Inhibiting EGFR Signaling Pathway in Breast Cancer Cells.

The present study was carried out to evaluate the anticancer property of an alkylamino phenol derivative -2-((3,4-Dihydroquinolin-1(2H)-yl)(p-tolyl)methyl)phenol) (THTMP) against human breast cancer cells. The cytotoxicity of the THTMP was assessed to know its specificity towards breast cancer cells without affecting the normal cells. The THTMP was synthesized and the cytotoxicity was assessed by MTT assay, Caspases enzyme activity, DNA fragmentation and FITC/Annexin V, AO/EtBr staining, RT-PCR and QSAR. In addition, ADME analysis was executed to understand the mode of action of THTMP. THTMP showed potential cytotoxic activity against the growth of MCF7 and SK-BR3 cells with the IC50 values of 87.92μM and 172.51μM, respectively. Interestingly, THTMP found to activate caspase 3 and caspase 9 enzymes in cancer cells, which are the key enzymes implicated in apoptosis. THTMP induced apoptosis in which 33% of the cells entered the late apoptotic stage after 24h of treatment. The results also revealed that the apoptotic response could be influenced by the association of THTMP with the Epidermal Growth Factor Receptor (EGFR) mediated inhibition of the Phosphatidylinositol 3-Kinase (PI3K)/S6K1 signaling pathway. In addition, docking was performed to study the binding mode of the THTMP, which shows better interaction with EGFR. The structural elucidation of THTMP by Quantitative Structure-Activity Relationship model (QSAR) and ADMET screening suggested, THTMP as an effective anticancer compound. This work strengthens the potential of a promising drug-like compound, THTMP, for the discovery of anticancer drug against breast cancer.

Bacterial expression of 183-227aa region of HER3 extracellular domain I and preparation and identification of its polyclonal antibodies

To prepare the recombinant peptide MVF-HER3 I composed of the 183-227aa peptide segment of human epidermal growth factor receptor 3 (HER3 I) and the measles virus protein 288-302 peptide segment (MVF), and prepare polyclonal antibodies (PcAb) against this recombinant peptide. The MVF-HER3 I gene was synthesized chemically and subcloned into pET21b or pET32a plasmid containing Thioredoxin (Trx) tag gene. The recombinant plasmids were identified by endonuclease digestion. MVF-HER3 I was expressed in E.coli BL21(DE3) cells under an optimal bacterial expression condition. The fusion protein Trx-MVF-HER3 I was purified using nickel ion affinity chromatography, and the purified protein was digested by enterokinase to remove Trx tag. The digested mixture underwent further nickel ion affinity chromatography to obtain purified MVF-HER3 I. The purified MVF-HER3 I was used to immunize SD rats subcutaneously for preparing anti-MVF-HER3 I PcAb. The titer of PcAb was determined using ELISA. The bindings of anti-MVF-HER3 I PcAb to MVF-HER3 I, native HER3 and MCF7 cells were analyzed using immunoblotting, immunoprecipitation and laser confocal microscopy. The growth inhibition effect of the antibodies on MCF7 cells cultured in the absence or presence of NRG was assessed using sulforhodamine B. The recombinant peptide gene could not be expressed alone, but could be efficiently expressed after fusion with Trx gene under optimized conditions. The fusion peptide MVF-HER3 I was successfully prepared from Trx-MVF-HER3 I. The anti-MVF-HER3 I PcAb, with a titer reaching 1: 512 000, specifically bound to MVF-HER3 I, recognized native HER3 and bound to the membrane of MCF7 cells. The obtained PcAb could dose-dependently inhibit the growth of MCF7 cells irrespective of the presence or absence of NRG. We successfully obtained the recombinant peptide MVF-HER3 I and prepared its PcAb, which can facilitate further functional analysis of HER3 signaling pathway.

A Novel Circular RNA hsa_circRPPH1_015 Exerts an Oncogenic Role in Breast Cancer by Impairing miRNA-326-Mediated ELK1 Inhibition.

Background: Breast cancer (BC) represents a heterogeneous disease with distinct subtypes and high tumor metastatic potentials. Recent researchers identify the implication of circular RNAs (circRNAs) in the initiation of BC. Herein, we uncover a novel circRNA hsa_circRPPH1_015 as a tumor promoter in BC.Methods: A total of 86 paired cancerous and non-cancerous tissues were surgically resected and collected from BC patients. Cell proliferation, colony formation, and cell invasion were examined by Edu staining, clone formation assays, propidium iodide (PI)-labeled flow cytometry, and Transwell invasion assays. PCNA, Ki67, MMP-2, MMP-9, Cyclin D1, and CDK4 expression was assayed using Western blot analysis. RNA pull-down, dual-luciferase reporter gene assay, and RNA binding protein immunoprecipitation (RIP) assay were performed to investigate the relationships among hsa_circRPPH1_015, microRNA-326 (miR-326), and ELK1. The tumor growth of human BC MCF-7 cells in vivo was evaluated in nude mice by subcutaneous xenografts of MCF-7 cells.Results: hsa_circRPPH1_015 expression was upregulated in BC tissues. Knockdown of hsa_circRPPH1_015 restrained the aggressive behavior of MCF-7. hsa_circRPPH1_015 could bind to miRNA-326 that negatively regulates ELK1. Elevation of miRNA-326 expression resulted in inhibition of cell proliferation, colony formation, and cell invasion of MCF-7. Disturbance of miRNA-326 or overexpression of ELK1 restored the proliferation and aggressiveness in hsa_circRPPH1_015-depleted MCF-7 cells. Tumor growth of MCF-7 cells in vivo was reduced in nude mice lack of endogenous hsa_circRPPH1_015 expression.Conclusion: Overall, the present study demonstrates that hsa_circRPPH1_015 was an oncogene and unfavorable prognostic factor in BC, providing an exquisite therapeutic target for BC.

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

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

Interaction of doxorubicin hydrochloride in the presence of, mixed aggregate of ibuprofen sodium and cationic lipid

This research was highlighted the importance of mixed aggregates based on drug-lipid to improve the interaction of one or more drugs in aqueous medium. This mixed aggregate can significantly inhibit the growth of MCF-7 cells, and has great potential for anti-inflammatory and cancer treatment after tumor removal. The cationic lipid (CL) has been synthesized with multistep reaction and is characterized by 1H NMR and mass spectroscopy. CL and ibuprofen (IBF) physiochemical analysis was investigated using surface tension, conductance, dynamic light scattering (DLS), and electron microscope transmission (TEM). The strong synergism between mixed aggregate (LIB) system CL and IBF was observed. The study on UV spectroscopy measured that the LIB mixed aggregate showed optimum binding to doxorubicin hydrochloride (DOX) and the binding constant Log Kb was 6.17 compared to single CL, the Log Kb was 5.83. Binding results indicated that the DOX was more encapsulated in mixed LIB aggregates compared to single CL aggregates. This mixed aggregate LIB has excellent performance in controlling the release of drugs. For single CL aggregate, approximately 62.5% DOX was released after 72 h (pH = 7.4). However, LIB such as, (0.1αCL+ 0.9αIBF), the release of DOX decreased to 16.08%. Finally, LIB mixed aggregate applicability has been used to minimize the cytotoxicity of MCF-7 cells, and it has been found that DOX in LIB mixed aggregates has a higher inhibitory effect on cell growth than DOX in CL.

Cell Theranostics on Mesoporous Silicon Substrates.

The adhesion, proliferation, and migration of cells over nanomaterials is regulated by a cascade of biochemical signals that originate at the interface of a cell with a substrate and propagate through the cytoplasm to the nucleus. The topography of the substrate plays a major role in this process. Cell adhesion molecules (CAMs) have a characteristic size of some nanometers and a range of action of some tens of nanometers. Controlling details of a surface at the nanoscale—the same dimensional over which CAMs operate—offers ways to govern the behavior of cells and create organoids or tissues with heretofore unattainable precision. Here, using electrochemical procedures, we generated mesoporous silicon surfaces with different values of pore size (PS ≈ 11 nm and PS ≈ 21 nm), roughness (Ra ≈ 7 nm and Ra ≈ 13 nm), and fractal dimension (Df ≈ 2.48 and Df ≈ 2.15). Using electroless deposition, we deposited over these substrates thin layers of gold nanoparticles. Resulting devices feature (i) nanoscale details for the stimulation and control of cell assembly, (ii) arrays of pores for drug loading/release, (iii) layers of nanostructured gold for the enhancement of the electromagnetic signal in Raman spectroscopy (SERS). We then used these devices as cell culturing substrates. Upon loading with the anti-tumor drug PtCl (O,O′-acac)(DMSO) we examined the rate of adhesion and growth of breast cancer MCF-7 cells under the coincidental effects of surface geometry and drug release. Using confocal imaging and SERS spectroscopy we determined the relative importance of nano-topography and delivery of therapeutics on cell growth—and how an unbalance between these competing agents can accelerate the development of tumor cells.

Heregulin controls ERα and HER2 signaling in mammospheres of ERα-positive breast cancer cells and interferes with the efficacy of molecular targeted therapy

Estrogen receptor (ER)α and the human epidermal growth factor receptor (HER) family are inversely expressed in ERα-positive cancer in association with resistance to hormonal therapy, but the mechanism underlying their relationship remains unknown. We analyzed the effect of HER family ligands on the expression of ER and the HER family in ERα-positive MCF-7 and T47D breast cancer cell lines in 3D spheroid culture. Here, we demonstrated for the first time that heregulin-1β (HRG), a HER3 and HER4 ligand, most effectively regulated ER/HER family expression by decreasing ERα mRNA expression and increasing HER family mRNA expression. HRG treatment attenuated fulvestrant-mediated growth inhibition, and promoted the migration of MCF-7 cells. Moreover, HRG increased the CD44+/CD24− cell fraction and side population cells, both of which are recognized as prospective breast cancer stem cell markers. HRG activated both phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) and mitogen-activated protein kinase (MAPK) pathways. Inhibitors of these pathways reduced the growth of MCF-7 cells, but the addition of HRG has different effects on these pathways. HRG blocked the inhibitory effect of mTOR inhibitors, such as rapamycin and everolimus, on cell growth but not that of a PI3K inhibitor. Furthermore, HRG slightly decreased the inhibitory effect of an AKT inhibitor on cell growth. In contrast, HRG enhanced the MEK inhibitor-induced inhibition of cell growth. These findings suggest that HRG-stimulated signaling pathways allow ERα-positive breast cancer cells to escape from growth inhibition caused by everolimus, via MAPK signaling and/or other signaling pathways. Everolimus improves progression-free survival in combination with exemestane as second-line therapy for metastatic hormone receptor-positive breast cancer. Our study suggests that HRG is a novel target for ERα-positive breast cancer therapy.

Design, synthesis, and biological evaluation of 4-substituted-3,4-dihydrobenzo[h]quinoline-2,5,6(1H)-triones as NQO1-directed antitumor agents

A novel series of 4-substituted-3,4-dihydrobenzo[h]quinoline-2,5,6(1H)-triones as NQO1-directed antitumor agents were designed, synthesized, biologically evaluated. Compounds 3n, 3o and 3j proved to be good NQO1 substrates that showed increased metabolic rates relative to that of β-lapachone. In addition, 3n, 3o and 3j potently inhibited the growth of NQO1-rich breast cancer MCF-7 cell, liver hepatocellular HepG2 cell, and lung cancer A549 cell. In cellular mechanistic studies, the representative compound 3o triggered ROS generation depending on the NQO1 dose, and induce HepG2 cell apoptosis by the generated oxidative stress. In HepG2 xenografts mouse model, at the dose of 20 mg/kg, 3o remarkably suppressed the tumor growth without affecting the animal weights.

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

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

Synthesis of New Thioureas Derivatives and Evaluation of Their Efficacy as Proliferation Inhibitors in MCF-7 Breast Cancer Cells by Using 99mTc-MIBI Radiotracer.

Anti-tumor activity of some thioureas derivatives is well documented in literature and received considerable attention. The present study aims to synthesize and characterize some novel thioureas and carbonylthioureas as anti-tumor agents for MCF-7 breast cancer cells in vitro and in vivo. Several 1-allyl-3-(substituted phenyl), N,N'-(phenylene) bis(3- allyldithithiourea) and 1-cyclopropanecarbonyl-3-(substituted phenyl)-thioureas derivatives were synthesized and confirmed by FT-IR spectroscopy, NMR and 13C-NMR. Anti-tumor activity of these compounds was determined by various in vitro and in vivo assays including; MTT, tumor volume measurement as well as,99mTc-MIBI tumor uptake in MCF-7 tumor bearing nude mice. Among all of the synthesized compounds, some thioureas derivatives [3i] and [4b] at 100 nM concentration exhibited significant inhibitory effects on the proliferation of MCF-7 cell in vitro. However, this inhibition was not observed in HUVEC human endothelial normal cells. In vivo anti-tumor effects of the synthesized compounds on MCF-7 xenograft mouse models demonstrated a reduction in the tumor volume for various concentrations between 2 to 10 mg/kg after 21 days. These effects were comparable with Tamoxifen as standard anti-estrogen drug. According to the 99mTc-MIBI biodistribution result, treatment of MCF-7 bearing nude mice with both [3i] and [4b] compounds at the maximum concentration (10 mg/kg) can lead to a significant decrease of 99mTc- MIBI tumor uptake. Compounds [3i] and [4b] suppressed the growth of MCF-7 cells in the xenograft nude mice at the doses that were well-tolerated. Our study suggests that these new compounds with their significant anti-tumor effects, may serve as useful candidates for breast cancer therapy.

Apolipoprotein-mediated regulation of lipid metabolism induces distinctive effects in different types of breast cancer cells

BackgroundThe highest incidence of breast cancer is in the Western world. Several aspects of the Western lifestyle are known risk factors for breast cancer. In particular, previous studies have shown that cholesterol levels can play an important role in the regulation of tumor progression.MethodsIn the present study, we modulated cholesterol metabolism in the human breast cancer cell lines MCF-7 and MDA-MB-231 using a genetic approach. Apolipoprotein A-I (apoA-I) and apolipoprotein E (apoE) were expressed in these cell lines to modulate cholesterol metabolism. The effects of these apolipoproteins on cancer cell properties were examined.ResultsOur results show that both apolipoproteins can regulate cholesterol metabolism and can control the epithelial-to-mesenchymal transition process. However, these effects were different depending on the cell type. We show that expressing apoA-I or apoE stimulates proliferation, migration, and tumor growth of MCF-7 cells. However, apoA-I or apoE reduces proliferation and migration of MDA-MB-231 cells.ConclusionsThese data suggest that modulating sterol metabolism may be most effective at limiting tumor progression in models of triple-negative cancers.

Structural characterization, antiproliferative and immunoregulatory activities of a polysaccharide from Boletus Leccinum rugosiceps

A homogeneous water-soluble flaky polysaccharide named LRP-1 (18.82 kDa) was extracted and purified from the rare edible and medicinal fungi Leccinum rugosiceps. The structure characterization of LRP-1 was analyzed by GPC, GC, GC–MS, FT-IR, SEM, 1D/2D NMR, and its antitumor and immunoregulatory activities were determined. The results show that LRP-1 is a new polysaccharide with a backbone which is mainly composed of →1-α-D-Fucp-3→, →1-α-D-Rhap-3→, →1-β-D-Glcp-6→, →1-β-D-Glcp-3→, →1-α-D-Glcp-4→, →1-β-D-Galp-6 → and →1-α-D-Manp-6→. Results of MTT assay show that LRP-1 inhibit the growth of human hepatoma cells HepG-2 and human breast carcinoma MCF-7 cells in vitro. LRP-1 could also induce the secretion of NO and immune factors (IL-6 and TNF-α) of RAW264.7. This study suggests that LRP-1 has potential to be used as nutraceutical food with antitumor and immunoregulatory activities.

Synthesis and screening of anticancer potentials of some new terephthaldehyde-derived nitrone compounds

Purpose: To synthesize and screen some new nitrone compounds derived from terephthaldehyde for their anticancer potential.&#x0D; Methods: Six new compounds (H, p-Me,p-Br, p-Cl, o-Cl and m-Me) were synthesized via a condensation reaction between terephthaldehyde and a variety of aryl hydroxylamine compounds derived from nitrobenzene and its derivatives. The chemical structures of these compounds were identified using elemental CHN analysis and were elucidated using Fourier Transform infra-red (FT-IR), 1H-nuclear magnetic resonance (1H NMR), mass spectrometry (MS), and elemental analysis. The anticancer effects of the compounds were screened in vitro with respect to their cytotoxicity on MCF7 human cancer cells line. The IC50 values were obtained by MTT assay and their effects on apoptosis of MCF-7 cells were assessed using Acridine orange-ethidium bromide AO/EtBr staining method under a fluorescence microscope.&#x0D; Results: Only four compounds (2b, 2d, 2e, and 2f) inhibited more than 50 % of the growth of MCF-7 cells. The strongest anti-proliferation effect against MCF-7 cells was exhibited by 2f (m-Me), producing more apoptosis which increased membrane disruption and consistency of lysosome vacuoles; it also exhibited higher cytotoxic effects on human cancer cell lines (IC50 &lt; 7.5) than the other synthesized compounds.&#x0D; Conclusion: The new nitrone compounds (2b, 2d, 2e, and 2f) synthesized from terephthaldehyde exhibit some anticancer properties, and so are potential anticancer agents.&#x0D; Keywords: Terephthaldehyde, Nitrone, Cytotoxicity, Anticancer, MCF-7 cells

TCRP1 induces tamoxifen resistance by promoting the activation of SGK1 in MCF‑7 cells.

Tamoxifen is widely used as a highly effective drug for treating estrogen-receptor (ER) alpha-positive breast cancer. However, tamoxifen resistance developed during cancer treatment remains a significant challenge. Tongue cancer resistance-related protein1 (TCRP1), which is recognized as a novel drug target, is related to chemo-resistance in human cancers, moreover, it is often overexpressed in various cancer cells, such as in lung cancer, breast cancer, and tongue cancer. However, the effects of TCRP1 on tamoxifen-resistant breast cancer cells and tissues are far from clear. The present study revealed that TCRP1 induced tamoxifen resistance in breast cancer cells. Western blotting, quantitative real-time polymerase chain reaction (RT-PCR) and immunohistochemical staining were performed to detect the expression level of TCRP1 in vivo and in vitro between primary breast cancer tissues and tamoxifen-resistant breast cancer tissues. The data revealed that the expression of TCRP1 was upregulated in the tamoxifen-resistant breast cancer tissues and human breast cancer cell line, MCF-7. Further study revealed that knocking down TCRP1 inhibited the growth of MCF-7 cells with tamoxifen-resistance (MCF7-R cells) and induced cell apoptosis. Moreover, TCRP1 promoted serum- and glucocorticoid-inducible kinase 1 (SGK1) activation via phosphorylation of phosphoinositide-dependent kinase 1 (PDK1) in MCF7-R cells. In addition, it was also observed that knocking down TCRP1 inhibited tumorigenesis of MCF-7 cells in nude mice. In conclusion, these data indicated that TCRP1 could induce tamoxifen resistance by regulating the PDK1/SGK1 signaling pathway. Thus, TCRP1 could be explored as a promising candidate for treating tamoxifen-resistant breast cancer in the future.

Phenolic Extract of Seagrass, Halophila ovalis Activates Intrinsic Pathway of Apoptosis in Human Breast Cancer (MCF-7) Cells

The marine ecosystem is considered as a treasure of numerous novel biologically active molecules. We investigated the anticancer potential of the phenolic extract of Halophila ovalis in breast cancer (MCF-7) cells and characterized the possible underlying molecular mechanism. The phenolic extract (5 µl) of H. ovalis effectively inhibited the growth of MCF-7 cells. The results of DAPI staining indicated that this phenolic extract potently induces apoptosis in MCF-7 cells which was observed by increased chromatin condensation in the treated cells. An increased expression of the active fragments of an executioner caspase, caspase 3 in phenolic extract-treated MCF-7 cells further confirms this apoptosis induction. In consequence, the loss of mitochondrial membrane potential was noticed in treated cells. The protein expression analyzes show decreased expression of the anti-apoptotic protein, Bcl-2, and DNA repair enzyme, PARP in treated cells indicating the probable molecular targets of apoptosis. Further, the phenolic extract of H. ovalis blocked the antioxidant defense system in MCF-7 cells by down-regulating the protein expression of a major transcription factor, Nrf-2 and regulatory antioxidant enzymes, SOD-2 and HO-1. These results show the presence of chemopreventive compound(s) in the phenolic extract, which offers a platform for future studies to identify the active principles.

Folic Acid-Modified Nanoerythrocyte for Codelivery of Paclitaxel and Tariquidar to Overcome Breast Cancer Multidrug Resistance.

The efflux of anticancer agents mediated by P-glycoprotein (P-gp) is one of the main causes of multidrug resistance (MDR) and eventually leads to chemotherapy failure. To overcome this problem, the delivery of anticancer agents in combination with a P-gp inhibitor using nanocarrier systems is considered an effective strategy. On the basis of the physiological compatibility and excellent drug loading ability of erythrocytes, we hypothesized that nanoerythrocytes could be used for the codelivery of an anticancer agent and a P-gp inhibitor to overcome MDR in breast cancer. Herein, a folic acid-modified nanoerythrocyte system (PTX/TQR NPs@NanoRBC-PEG/FA) was prepared to simultaneously transport paclitaxel and tariquidar, and the in vitro and in vivo characteristics of this delivery system were evaluated through several experiments. The results indicated that the average diameter and surface potential of this nanocarrier system were 159.8 ± 1.4 nm and -10.98 mV, respectively. Within 120 h, sustained release of paclitaxel was observed in both pH 6.5 media and pH 7.4 media. Tariquidar release from this nanocarrier suppressed the P-gp function of MCF-7/Taxol cells and significantly increased the intracellular paclitaxel level (p < 0.01 versus the PTX group). The results of the MTT assay indicated that the simultaneous transportation of paclitaxel and tariquidar could significantly inhibit the growth of MCF-7 cells or MCF-7/Taxol cells. After 48 h of incubation with PTX/TQR NPs@NanoRBC-PEG/FA, the viability of MCF-7 cells and MCF-7/Taxol cells decreased to 7.37% and 30.2%, respectively, and the IC50 values were 2.49 μM and 6.30 μM. Pharmacokinetic results illustrated that, compared with free paclitaxel, all test paclitaxel nanoformulations prolonged the drug release time and showed similar plasma concentration-time profiles. The peak concentration (Cmax), area under the curve (AUC0-∞), and half-life (t1/2) of PTX/TQR NPs@NanoRBC-PEG/FA were 3.33 mg/L, 6.02 mg/L·h, and 5.84 h, respectively. Moreover, this active targeting nanocarrier dramatically increased the paclitaxel level in tumor tissues. Furthermore, compared with those of the other paclitaxel formulations, the cellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels of the PTX/TQR NPs@NanoRBC-PEG/FA group increased by 1.38-fold (p < 0.01) and 1.36-fold (p < 0.01), respectively, and the activities of superoxide dismutase (SOD) and catalase (CAT) decreased to 67.8% (p < 0.01) and 65.4% (p < 0.001), respectively. More importantly, in vivo antitumor efficacy results proved that the PTX/TQR NPs@NanoRBC-PEG/FA group exerted an outstanding tumor inhibition effect with no marked body weight loss and fewer adverse effects. In conclusion, by utilizing the inherent and advantageous properties of erythrocytes and surface modification strategies, this biomimetic targeted drug delivery system provides a promising platform for the codelivery of an anticancer agent and a P-gp inhibitor to treat MDR in breast cancer.

Cytotoxic effect of Spirulina platensis extract and Ulva compressa Linn. on cancer cell lines

Studies have shown that algae and seaweed have cytotoxic activity. This study was aimed to determine the cytotoxic activity of Spirulina platensis and Ulva compressa Linn. extracts against cancer cell lines. The cytotoxic activity of the extract was carried out using the MTT ((3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. Results showed that the ethanol extract and methanol extract of Spirulina platensis have no cytotoxic effect against HeLa, WiDr, MCF7 and T47D cells. Water extract of Spirulina platensis had no cytotoxic activity on T47D and Vero cells. Water extracts of Spirulina platensis increase MCF7 cell growth. Phycocyanin powder also stimulates MCF7 cell growth. Ethanol extract of Ulva compressa Linn. exhibited potentially cytotoxic activity against MCF7 and moderate cytotoxic against WiDR cells with IC50 values are 31.86 μg/ mL and 104.93 μg/mL, respectively. It can be concluded that extract of Spirulina platensis has no potential to be developed for cancer therapy. Ulva compressa Linn has the potential to be developed as an anti-cancer. Further research for study the mechanism of anticancer of Ulva compressa Linn on MCF7 was needed.

Efficient biosynthesis of CuO nanoparticles with potential cytotoxic activity

Biogenic CuO nanoparticles (CuO-NPs) were greenly synthesized utilizing two precursors of waste plant extracts, namely pomegranate peel [PP] and date stones [DS], to enhance its cytotoxic activity. The biogenic CuO-NPs produced from pomegranate peel extract [PP-CuO-NPs] have been found in an excessively small nanosized structures [~ 6 nm] compared to that prepared from the date stones extract [~ 20 nm] D-CuO-NPs. The two products [PP-CuO-NPs and D-CuO-NPs] obtained were fully characterized. The agglomeration and crystal formation of biogenic CuO-NPs were investigated by transmission electron microscopy, scanning electron microscopy, and X-ray diffraction analysis. Fourier transform infrared spectroscopy and thermogravimetric analysis–derivative thermogravimetric analysis were utilized to determine the existence of working groups absorbed on the biogenic CuO-NPs surface, while the dispersion stability of CuO-NPs was assessed through zeta potential test. The validity of the biogenic CuO-NPs as cytotoxic agent was applied against human breast cancer [MCF7] cell lines and compared with the normal BJ1 cell line. The results demonstrated a discriminative inhibition of cancer cell growth of MCF7, particularly by using PP-CuO, decreasing to nearly 0.0%.

23P Novel ERα degrader, 3,20(R)-dihydroxy-19-norpregnatriene, inhibits MCF-7 cell growth through p21/CDK2/CDK4 pathway

23P Novel ERα degrader, 3,20(R)-dihydroxy-19-norpregnatriene, inhibits MCF-7 cell growth through p21/CDK2/CDK4 pathway

Autocrine motility factor secreted by HeLa cells inhibits the growth of many cancer cells by regulating AKT/ERK signaling

In cell competition, a secreted death signal can determine cell fate. However, the nature of such a signal remains unclear. In this study, conditioned medium from HeLa cells (HeLa CM) inhibited growth of A549 and MCF-7 cells. Through HeLa CM fractionation, glucose 6-phosphate isomerase/autocrine motility factor (GPI/AMF) was identified as the main growth inhibitor. Previously, AMF was known for its mitogenic, motogenic, and differentiation functions and was implicated in tumor progression and metastasis. HeLa CM lost its growth inhibitory property after treatment with erythrose-4-phosphate (E4P) or anti-GPI antibody. Purified HeLa recombinant AMF (rAMF) proteins inhibited the growth of A549, MDA-MB-232, MCF-7, AsPC-1, DU145, Hep-2, Hep G2, and HT-29 cells. However, growth of HL-60, SKOV3, U-87 MG, SNU-484, U-87 MG, and 3T3-L1 cells was little affected. In a Transwell assay, HeLa rAMF effectively reduced A549 cell migration and invasion. HeLa rAMF effectively induced apoptosis in A549 cells, apparently by reducing the levels of Bcl-2, GPI, and poly(ADP-ribose) polymerase (PARP)14 and activating caspase-3 and p53. HeLa rAMF antagonized HER2 and the AMF receptor (AMFR or GP78) in relation to the AKT/EKT signaling pathway. These results suggest that HeLa AMF could act as a diffusible death signal that could induce cancer cell–selective growth inhibition and apoptosis.