Proliferation Of MCF-7 Cancer Cells Research Articles

PDNA-tachyplesin treatment stimulates the immune system and increases the probability of apoptosis in MC4-L2 tumor cells.

Breast cancer is the most common cancer among women worldwide, and marine creatures are the most abundant reservoir of anticancer medicines. Tachyplesin peptides have shown antibacterial capabilities, but their potential to inhibit cancer growth and trigger cancer cell death has not been investigated. A synthetic tachyplesin nucleotide sequence was generated and inserted into the pcDNA3.1( +) Mammalian Expression Vector. PCR analysis and enzyme digesting procedures were used to evaluate the vectors' accuracy. The transfection efficiency of MCF-7 and MCF10-A cells was 57% and 65%, respectively. The proliferation of MCF-7 cancer cells was markedly suppressed. Administration of plasmid DNA (pDNA) combined with tachyplesin to mice with tumors did not cause any discernible morbidity or mortality throughout treatment. The final body weight curves revealed a significant reduction in weight among mice treated with pDNA/tachyplesin and tachyplesin at a dose of 100 µg/ml (18.4 ± 0.24 gr, P < 0.05; 11.4 ± 0.24 gr P < 0.01) compared to the control group treated with PBS (22 ± 0.31 gr). Animals treated with pDNA/tachyplesin and tachyplesin exhibited a higher percentage of CD4 + Foxp3 + Tregs, CD8 + Foxp3 + Tregs, and CD4 + and CD8 + T cell populations expressing CTLA-4 in their lymph nodes and spleen compared to the PBS group. The groups that received pDNA/tachyplesin exhibited a substantial upregulation in the expression levels of caspase-3, caspase-8, BAX, PI3K, STAT3, and JAK genes. The results offer new possibilities for treating cancer by targeting malignancies using pDNA/tachyplesin and activating the mTOR and NFκB signaling pathways.

Autophagy induction using Resveratrol enhances the anti-cancer efficacy of Doxazosin in breast cancer cells.

The combination of anti-cancer drugs improves effectiveness compared to the mono-therapy scenario by targeting key pathways synergistically or in an additive way. Doxazosin (DOX) and Resveratrol (RES) are reported to have an anti-cancer impact against different cancer cells. Aim: To evaluate the anti-cancer properties of Doxazosin and Resveratrol, each alone or in combination, in inhibiting breast cancer cell proliferation. Methods: MCF-7 cancer cells were seeded to a confluent monolayer and treated with 100, 50, 25, 12.5, 6.25, and 3.12 µM of each drug alone and as a combination. Cytotoxicity was evaluated using dimethyl thiazolyl diphenyl tetrazolium salt (MTT) assay and colony formation assay. The immunocytochemistry technique was conducted to evaluate caspase-3 and GABARAP expression. Results: All the drugs have a significant effect on cancer cell proliferation. The combination treatment of Doxazosin-Resveratrol has a more cytotoxic effect than each drug alone, as well as in colony formation of MCF-7 cancer cells. In combination treatment, caspase-3 had a higher expression pattern than other treatments. Resveratrol treatment elevated GABARAP expression in cancer cells, indicating the induction of the autophagy process. Conclusion: Although each drug has its characteristic result of a cytotoxic effect, the combination of Doxazosin and Resveratrol synergizes the inhibition of MCF-7 cancer cell proliferation. Keywords: Resveratrol; Doxazosin; combination; MCF-7; Autophagy.

Synthesis, Characterization, and Anticancer Activity of New N,N'-Diarylthiourea Derivative against Breast Cancer Cells.

The goal of the current study was to prepare two new homologous series of N,N'-diarylurea and N,N'-diarylthiourea derivatives to investigate the therapeutic effects of these derivatives on the methodologies of inhibition directed on human MCF-7 cancer cells. The molecular structures of the prepared derivatives were successfully revealed through elemental analyses, 1H-NMR, 13C-NMR and FT-IR spectroscopy. The cytotoxic results showed that Diarylthiourea (compound 4) was the most effective in suppressing MCF-7 cell growth when compared to all other prepared derivatives, with the most effective IC50 value (338.33 ± 1.52 µM) after an incubation period of 24 h and no cytotoxic effects on normal human lung cells (wi38 cells). Using the annexin V/PI and comet tests, respectively, treated MCF-7 cells with this IC50 value of the Diarylthiourea 4 compound displayed a considerable increase in early and late apoptotic cells, as well as an intense comet nucleus in comparison to control cells. An arrest of the cell cycle in the S phase was observed via flow cytometry in MCF-7 cells treated with the Diarylthiourea 4 compound, suggesting the onset of apoptosis. Additionally, ELISA research showed that caspase-3 was upregulated in MCF-7 cells treated with compound 4 compared to control cells, suggesting that DNA damage induced by compound 4 may initiate an intrinsic apoptotic pathway and activate caspase-3. These results contributed to recognizing that the successfully prepared Diarylthiourea 4 compound inhibited the proliferation of MCF-7 cancer cells by arresting the S cell cycle and caspase-3 activation via an intrinsic apoptotic route. These results, however, need to be verified through in vivo studies utilizing an animal model.

Comparative studies on selection of high polyphenolic containing Chinese raspberry for evaluation of antioxidant and cytotoxic potentials

The Chinese raspberry (Rubus chingii Hu) fruit is well-recognized for its special pharmacological qualities. We examined the polyphenolic constituents in twelve Chinese raspberries (B1–B12), out of which B1 raspberry showed high content of phenolics, flavonoids and anthocyanins in total, compared to other raspberry samples we collected. Further, B1 raspberry sample explored for its antioxidant and cytotoxic effects. The results showed that the total polyphenolic content in the ethanol extract (11.47 mg/g) was greater than in the water extract (WE) (7.78 mg/g); the polysaccharide content in the EE (587.78 mg/g) was also found to exceed that of the WE (476.24 mg/g) revealing the presence of 18.91 mg/g anthocyanin in total. Of interest, in terms of the total flavonoid content, no significant results were noted. Further, potential antioxidant activity against DPPH and ABTS radical scavenging was seen in the B1 extracts giving EC50 values of 1.37 and 0.94 mg/mL (EtOH extract) and 2.55 and 1.93 mg/mL (aqueous extract), respectively. From the cytotoxic study employing several types of cancer cell lines, a significant inhibition effect was seen by the B1 EE on the SKOV3 and MCF-7 cancer cell proliferation; however, no cytotoxic effects were noted on the A549 and Hela cells. Therefore, the findings of the current study imply that the R. chingii (B1) has the potential to be utilized as a therapeutic agent, in light of its antioxidant and cytotoxic effects against cancer cell lines. Even so, further research is required to confirm the effective isolation of the bioactive compound.

Antiproliferative Effect of Polysaccharide Fraction of Astragalus Ovinus Against MCF-7 Cancer Cell Line

Background: The effect of Astragalus has been recognized in traditional Chinese medicine, and the roots are believed to have anti-cancer properties. This study investigated the effects of the ethanolic extract and polysaccharide fraction of Astragalus ovinus roots on MCF7 cell line. Methods: We used MTT assay to evaluate the cytotoxicity of A. ovinus roots. The status of cell cycle and apoptosis were examined, using flow cytometry. The gene expressions related to the extrinsic and intrinsic apoptotic pathways (caspases 8 &amp; 9) were also examined by real-time polymerase chain reaction (PCR). Results: The cytotoxicity data showed that the A. ovinus extract inhibited the proliferation of MCF7 cancer cells in a dose-dependent manner. The IC50 of Cisplatin , ethanolic extract and polysaccharides fraction were 22.42, 560.9, and 961.2 in µg/ml, respectively. Also, the cell cycle analysis showed that the ethanolic extract and polysaccharide fractions arrested the cell cycle in the G1 phase. Examination of the apoptotic effects showed that treatment with either the A. ovinus extract or the polysaccharide fraction induced apoptosis in MCF-7 cancer cells. The expression of caspases 8 and 9 genes was inhibited after exposure to either cisplatin or the polysaccharide fraction (PFA). However, treatment with the extract inhibited only the caspase-8 gene expression. Conclusion: The results confirmed that treatment with the extract and polysaccharide fraction caused anti-proliferative effect and apoptosis of MCF-7 cell line. Therefore, it can be concluded that the A. ovinus extract and the polysaccharides have potential therapeutic effects against human breast cancer cells.

Synergistic Effect of Quercetin Magnetite Nanoparticles and Targeted Radiotherapy in Treatment of Breast Cancer.

Quercetin is a potent cancer therapeutic agent present in fruits and vegetables. The pharmaceutical uses of quercetin are limited due to many problems associated with low solubility, bioavailability, permeability, and instability. In addition, the high doses of quercetin show toxic effects in clinical and experimental studies. Therefore, a new strategy is warranted to overcome these problems without the use of toxic doses. The iron oxide nanoparticles can be used as a drug delivery system. This study aimed to prepare quercetin-conjugated magnetite nanoparticles (QMNPs) using biological simple nanoprecipitation and mediated by fungus Aspergillus oryzae. Also, we initiated in vitro and in vivo studies to determine whether QMNPs might sensitize breast cancer to radiotherapy treatment. The structural, morphological, and magnetic properties of the prepared nanoparticles were studied. The results indicated that QMNPs were spherical in shape and 40 nm in diameter. The in vitro studies showed that the incubation of MCF-7, HePG-2, and A459 cancer cells with QMNPs for 24 h effectively inhibited the growth of cancer cell lines in a concentration-dependent manner with IC50 values of 11, 77.5, and104 nmol/mL, respectively. The combination of QMNPs with irradiation (IR) potently blocked MCF-7 cancer cell proliferation and showed significant changes in the morphology of these cells as observed by bright-field inverted light microscopy. Focusing on the long-term toxicity of QMNPs (20 ml/kg), the assessment of hematological, hepatic, and renal markers indicated no toxic effect. Besides, QMNPs inhibited tumor growth and potently enhanced the lateral radiotherapy treatment in N-methyl-N-nitrosourea (MNU)-induced breast cancer in female white albino rats. These anticancer and radiosensitizing activities were ascribed to cytotoxicity, cell cycle arrest, immunomodulation, and efficiency through induction of apoptosis. In a conclusion, these observations suggest that the QMNPs combined with LRT could act as a potential targeted therapy in breast cancer.

Uracil-coumarin based hybrid molecules as potent anti-cancer and anti-bacterial agents

In the current report, we have rationally designed a series of uracil-coumarin based bifunctional molecular hybrids roped by 1,2,3-triazole moiety. The designed compounds were synthesized and tested against a panel of six human cancer cell lines namely Colo-205, MCF-7, A-549, PA-1, PC-3 and Hela cells by Sulforhodamine B assay. The results indicated that the hybrid molecules can specifically inhibit the MCF-7 cancer cell proliferation amongst which A-2 was found to be most potent hybrid (GI50 = 1.55 µM) with fluorine atom as R with two carbon chain length between triazole and coumarin moieties. Cell cycle analysis revealed that A-2 significantly arrest the G2/M phase to inhibit proliferation of MCF-7 cells. Due to its mitotic arrest, A-2 was further analyzed to predict its various binding interactions within the active site of tubulin, which revealed its best binding pattern within the vinblastine binding site. In addition to this, antibacterial potential of all the synthetics was also evaluated which resulted in two hit lead molecules A-2 (MIC = 11.7 μg/mL) and A-3 (MIC = 7.23 μg/mL) that can significantly inhibit the bacterial strain Staphylococcus aureus comparable to that of standard drug levofloxacin (MIC = 3.12 μg/mL). Binding interactions within the active site of dihydrofolate reductase (DHFR) were also streamlined by using molecular docking studies. Overall studies revealed some interesting features of synthetics to be active which stated that, the compounds with electronegative atom on R and compounds with two carbon chain length between triazole and coumarin showed best results.

PPAR Receptors Expressed from Vectors Containing CMV Promoter Can Enhance Self-Transcription in the Presence of Fatty Acids from CLA-Enriched Egg Yolks—A Novel Method for Studies of PPAR Ligands

PPAR receptors are ligand-dependent transcription factors activated in response to various small lipophilic ligands controlling the expression of different genes involved in cellular differentiation, development, metabolism, and tumorigenesis. Unexpectedly, our previous studies have shown that single plasmid-based expression of PPARs under the control of CMV promoter/enhancer was significantly elevated in the presence of PPAR agonists. Here we show that the PPAR reporters controlled by the CMV promoter/enhancer, that was shown to contain three internal non-canonical PPRE elements, can be used as a fast screening system for more effective PPAR ligands. This model allowed us to confirm our previous results indicating that fatty acids of CLA-enriched egg yolks (EFA-CLAs) are efficient PPAR ligands that can specifically upregulate the expression of PPARα and PPARγ leading to downregulation of MCF-7 cancer cell proliferation. We also show that synthetic cis9,trans11CLA is more effective in transactivation of PPARγ, while trans10,cis12CLA of PPARα receptor indicating the selectivity of the CLA isomers. This report presents a novel, fast, and reliable strategy for simple testing of PPAR ligands using PPAR expressing plasmids containing the CMV promoter/enhancer that can trigger the positive feedback loop of PPAR self-transcription in the presence of PPAR ligands.

Synthesis and biological evaluation of 4-(1H-1,2,4-triazol-1-yl)benzoic acid hybrids as anticancer agents.

A series of 4-(1H-1,2,4-triazol-1-yl)benzoic acid hybrids (1–17) was successfully synthesized and their structures were established by NMR and MS analysis. In vitro cytotoxic evaluation indicated that some of the hybrids exhibited potent inhibitory activities against MCF-7 and HCT-116 cancer cell lines, with IC50 values ranging from 15.6 to 23.9 µM, compared with reference drug doxorubicin (19.7 and 22.6 µM, respectively). Notably, the most potent compounds, 2, 5, 14, and 15, not only exhibited an obvious improvement in IC50 values, but demonstrated very weak cytotoxic effects toward normal cells (RPE-1) compared with doxorubicin. A further investigation showed that compounds 2 and 14 clearly inhibited the proliferation of MCF-7 cancer cells by inducing apoptosis. In addition, these hybrids showed acceptable correlation with bioassay results in regression plots generated by 2D QSAR models. Our results indicated that 1,2,4-triazole benzoic acid hybrids could be used as a structural optimization platform for the design and development of more selective and potent anticancer molecules.

Development of Folate-Thioglycolate-Gold Nanoconjugates by Using Citric Acid-PEG Branched Polymer for Inhibition of MCF-7 Cancer Cell Proliferation.

Development of folate (FA)-functionalized gold nanoparticles (AuNPs) has greatly increased in recent years due to their potential in cancer treatment. As surface functionalization of polymer-free AuNPs with thiol groups could result in agglomeration and precipitation, AuNPs should be stabilized with an efficient polymer. In this study, citric acid-PEG branched polymer (CPEG) acted as a reducing as well as stabilizing agent in the synthesis of AuNPs. The thiol group of thioglycolic acid (TGA) attached to CPEG-stabilized AuNPs and interacted with the free carboxylic acid group on the surface of TGA-AuNP nanoconjugates. Stable TGA-AuNP nanoconjugates were obtained only with CPEG-stabilized AuNPs and not with citrate-stabilized AuNPs. The carboxylic acid group on the surface of AuNPs was used to attach FA via an EDC/NHS coupling reaction to obtain FA-TGA-AuNP nanoconjugates. In vitro cytotoxicity studies indicated that FA-TGA-AuNPs were not toxic to normal cells up to a concentration of 200 μg/mL. However, FA-TGA-AuNP nanoconjugates effectively inhibited proliferation of MCF-7 cancer cells at a low concentration of 25 μg/mL after 3 days of incubation. The anticancer activity of FA-TGA-AuNPs was enhanced by incorporating the anticancer drug 5-fluorouracil into the nanoconjugates, which exhibited sustained drug release up to 5 days. Hence, the developed biocompatible FA-TGA-AuNPs could be used for specific killing of breast cancer cells.

Inhibitory Activity of Iron Chelators ATA and DFO on MCF-7 Breast Cancer Cells and Phosphatases PTP1B and SHP2.

Rapidly-dividing cancer cells have higher requirement for iron compared to non-transformed cells, making iron chelating a potential anticancer strategy. In the present study we compared the anticancer activity of uncommon iron chelator aurintricarboxylic acid (ATA) with the known deferoxamine (DFO). We investigated the impact of ATA and DFO on the viability and proliferation of MCF-7 cancer cells. Moreover we performed enzymatic activity assays and computational analysis of the ATA and DFO effects on pro-oncogenic phosphatases PTP1B and SHP2. ATA and DFO decrease the viability and proliferation of breast cancer cells, but only ATA considerably reduces the activity of PTP1B and SHP2 phosphatases. Our studies indicated that ATA strongly inactivates and binds in the PTP1B and SHP2 active site, interacting with arginine residue essential for enzyme activity. We confirmed that iron chelating can be considered as a potential strategy for the adjunctive treatment of breast cancer.

Hypoxia‐induced carbonic anhydrase IX facilitates lactate transport in human breast cancer cells by non‐catalytic interaction

The most aggressive and invasive tumor cells, which often reside in hypoxic environments, rely on extensive glycolysis to meet their large demand for energy and biosynthetic precursors. Thereby they release vast amounts of lactate and protons via monocarboxylate transporters (MCTs), which exacerbates extracellular acidification and supports the formation of a hostile environment. We have studied the mechanisms that regulate lactate transport in MCF‐7 human breast cancer cells under normoxia and hypoxia. Under hypoxia, expression of MCT1 and MCT4 remained unchanged, while expression of carbonic anhydrase IX (CAIX) was greatly enhanced. Measurements of intracellular pH and lactate concentration with the FRET‐based lactate nanosensor laconic show that CAIX augments lactate flux via MCT1 by a non‐catalytic interaction. Mutation studies in Xenopus oocytes indicate that CAIX, via its intramolecular H+‐shuttle His200, functions as a “proton‐collecting/distributing antenna” to facilitate rapid lactate flux via MCT1. Knockdown of CAIX significantly reduced proliferation of MCF‐7 cancer cells, suggesting that rapid efflux of lactate and H+, as enhanced by CAIX, contributes to cancer cell survival under hypoxic conditions.This work was supported by the Research Initiative Membrane Biology, the Stiftung Rheinland‐Pfalz für Innovation, the Graduiertenfördungskommission Rheinland‐Pfalz, and the DFG.

Liposome encapsulation of curcumin: Physico-chemical characterizations and effects on MCF7 cancer cell proliferation

The role of curcumin (diferuloylmethane), for cancer treatment has been an area of growing interest. However, due to its low absorption, the poor bioavailability of curcumin limits its clinical use. In this study, we reported an approach of encapsulation a curcumin by nanoliposome to achieve an improved bioavailability of a poorly absorbed hydrophobic compound. We demonstrated that liposomal preparations to deliver curcumin increase its bioavailability. Liposomes composed of salmon's lecithin also improved curcumin bioavailability compared to those constituted of rapeseed and soya lecithins. A real-time label-free cell analysis system based on real-time cell impedance monitoring was used to investigate the in vitro cytotoxicity of liposomal preparations.