Human Cancer Cell Line MCF-7 Research Articles

Differential Effects of Punicic Acid on Cytotoxicity and Peroxiredoxin Expression in MCF-7 Breast Cancer and MCF-10A Normal Cells.

The pomegranate fruit has been associated with a variety of human health benefits based on its antioxidant and anti-inflammatory properties. Punicic acid (PA) is an omega-5 long chain polyunsaturated fatty acid that constitutes approximately 65-80% of the oil from pomegranate seeds and has been found to possesses anti-cancer activity in various cancer types. To better understand its cell specificity, we investigated the effects of punicic acid on both the MCF-7 human breast cancer cell line as well as the non-cancerous MCF-10A breast epithelial line. We treated both cell types with different concentrations of punicic acid and measured viable cell density, cytotoxicity and apoptosis, as well as peroxiredoxin (Prdx) antioxidant expression. We found that punicic acid was cytotoxic to both lines, but MCF-10A cells demonstrated higher levels of cytotoxicity and sensitivity to lower concentrations. We further demonstrated that cytotoxicity was associated with apoptosis in both lines. Using real time PCR, we demonstrated induction of all six Prdx mRNAs in MCF-7 cells, ranging from a 1.4-fold increase with 2 μg/ml, to over a 5-fold increase with 10 μg/ml. In stark contrast, MCF-10A cells exhibited considerably higher induction of all six Prdx mRNAs at 10μg/ml, exceeding a 30-fold induction of Prdx1, Prdx2 and Prdx5. Our data are the first to demonstrate differential cytotoxicity and Prdx regulation by punicic acid in these two cell lines. These results may provide important insight into cell-specific mechanisms of punicic acid in breast cancer.

Evaluation of Antioxidant and Breast Cancer Cytotoxicity of Beta vulgaris and Daucus carota Methanol Extracts

Breast cancer is the world's most frequent malignancy among women. Many dietary antioxidants have been shown to help prevent oxidative stress, which has been linked to a variety of diseases, including cancer. Many chronic diseases, such as cancer, can be avoided by eating fruits and vegetables on a regular and balanced basis. The current study's goal is to assess the antioxidant and cytotoxic capabilities of methanolic extracts of Beta vulgaris and Daucus carota against MCF-7 human breast cancer cell lines. Therefore, the aim of the present study was to determine the phytochemical components, antioxidant capacity, total phenolic & flavonoid contents in the methanolic extracts of Beta vulgaris and Daucus carota. Further, MTT assay against breast cancer cell line (MCF-7) was performed for the evaluation of cytotoxic activity. The majority of secondary metabolites were found in both the aqueous and methanolic extracts of Beta vulgaris and Daucus carota. Beta vulgaris and Daucus carota have different total phenolic and flavonoid contents. TLC results showed many spots having different Rf values. Moreover, we observe comparable cytotoxic activity in both the extracts against MCF-7 cell lines. Our results reveal that the methanolic extracts of Beta vulgaris and Daucus carota has effective phytochemical constituents, antioxidant and anticancer activity. The total phenolic and flavonoid contents vary between Beta vulgaris and Daucus carota. Further studies are needed to evaluate the chemopreventive potentials of the Beta vulgaris and Daucus carota extract when used alone or in combination with doxorubicin to mitigate the toxic side-effects of the latter.

Evaluation Secondary Metabolite Extract Produced by Aspergillus terreus Isolated from Poultry Droppings as Anticancer Agent

Malignant diseases are considered one of the problems of our time, and cancer is defined as the abnormal growth of malignant cells. It is widely accepted as the leading cause of death. There is currently no proven cancer cure. As a result, scientists have concentrated on creating secure and efficient therapies. Research has been done on the effects of naturally occurring substances that have been extracted from living things, such fungus on cancer cells. This study sought to determine the natural products' efficacy against human cancer cell line MCF-7. After A. terreus was isolated from samples of chicken droppings, it was grown on potato and Sabouraud Dextrose Agars (SDA and PDA) with chloramphenicol media. It was then identified using the extracted genomic DNA, the internal transcribed spacer (ITS) region was amplified and sequenced. After 30 days of incubation at 27°C, natural metabolite products were also recovered from the fermentation medium using the ethyl acetate extraction technique. The effectiveness of the fungal extract against the human cancer cell line MCF-7 and the normal human cell line NHF cell was also determined after incubation for 27 hours with the natural extract. The treated human cancer cell line MCF-7 showed decrease of proliferation, whereas the normal human cell line NHF showed no effect. Significant inhibitor compared to cancer line. The IC50 values for MCF-7 cell lines and NHF normal human cell lines were 7.672 and 1431 μg/mL, respectively. In summary, MCF-7 was affected by the natural extract extracted from A. terreus, in contrast to the control. When these results were combined, they showed that the fungal extract is an effective anti-cancer treatment.

In silico studies, synthesis, characterization and in vitro studies of levosulpiride derivatives.

Aim: Breast cancer is the most recurring cancer among females and is being diagnosed as a major cause of death among women.Materials & methods: Levosulpiride Schiff base derivatives were synthesized and analyzed by physical and spectral (FTIR, 1H-NMR, 13C-NMR) analysis. MTT assay against MCF-7 (human breast cancer cell line), scavenging activity and Molecular docking against receptors 1M17, 3PP0, 3IOK and 4KIK along ADME pharmacokinetic studies were performed.Results & conclusion: L1 and L3 synthesized derivatives have revealed better percent cell viability and inhibitory concentration (IC50) with scavenging activity as of the parent compound. L1, L3 and L9 revealed significant docking scores compared with standard drugs. Most of the derivatives showed strong pharmacokinetic profiles while no drug crossed blood-brain barrier. The newly synthesized L1 and L3 levosulpiride-derived compounds have demonstrated promising anticancer properties against breast cancer cells.

Study of Anti-proliferative Effect and Scratch Wound Migration Assay of Ethanol Extract of <i>Pyrus communis</i> L. Leaf on MCF-7 Model

Objectives: The current aim of the study was twofold: first, to identify the primary phytochemical compounds present in the ethanol extract derived from Pyrus communis L. leaves and second, to assess the extract’s anti-proliferative effect. Materials and Methods: The study conducted an in vitro anti-proliferative investigation of the P. communis leaves extract using the MTT using colorimetric assay against the MCF-7 cell line. These assays collectively provide insights into different aspects of cell behaviour, including proliferation, migration, and invasion, which are important in understanding the overall effect of the extract on the MCF-7 cell line. The protective effect observed in the analysis of the ethanol extract is attributed to the existence of flavonoids and phenols in the extract. Results: Total flavonoid and phenolic contents were observed as 56 mg of quercetin/g and 48 mg of gallic acid/g as standard. This extract ascertained cytotoxic against the MCF-7 cell line in a reverse dose-dependent manner. However, the extract is found to be more potent and effective against MCF-7 (human Breast cancer cell lines) with LC50 value 265.310978μg/ml. Conclusions: The in vitro cytotoxic activity of this extract of the plant leaves has been evaluated, revealing a significant anti-proliferative effect and suppression of cell migration against the MCF-7 cell line. This suggests that the extract may possess compounds or properties that inhibit cell proliferation followed by wound migration, which are crucial factors in cancer progression. This approach is motivated by the observed inhibitory effect of cancer cell proliferation and wound migratory effects of the extract against the MCF-7 cell line, as well as the epidemiological evidence suggesting its anti-carcinogenic potential. This avenue of research holds promise for enhancing the effectiveness of cancer therapy and improving patient outcomes.

Enhanced Synergistic Efficacy Against Breast Cancer Cells Promoted by Co-Encapsulation of Piplartine and Paclitaxel in Acetalated Dextran Nanoparticles.

Malignant breast tumors constitute the most frequent cancer diagnosis among women. Notwithstanding the progress in treatments, this condition persists as a major public health issue. Paclitaxel (PTX) is a first-line classical chemotherapeutic drug used as a single active pharmaceutical ingredient (API) or in combination therapy for breast cancer (BC) treatment. Adverse effects, poor water solubility, and inevitable susceptibility to drug resistance seriously limit its therapeutic efficacy in the clinic. Piplartine (PPT), an alkaloid extracted from Piper longum L., has been shown to inhibit cancer cell proliferation in several cell lines due to its pro-oxidant activity. However, PPT has low water solubility and bioavailability in vivo, and new strategies should be developed to optimize its use as a chemotherapeutic agent. In this context, the present study aimed to synthesize a series of acetalated dextran nanoparticles (Ac-Dex NPs) encapsulating PPT and PTX to overcome the limitations of PPT and PTX, maximizing their therapeutic efficacy and achieving prolonged and targeted codelivery of these anticancer compounds into BC cells. Biodegradable, pH-responsive, and biocompatible Ac-Dex NPs with diameters of 100-200 nm and spherical morphologies were formulated using a single emulsion method. Selected Ac-Dex NPs containing only PPT or PTX as well as those coloaded with PPT and PTX achieved excellent drug-loading capabilities (PPT, ca. 11-33%; PTX, ca. 2-14%) and high encapsulation efficiencies (PPT, ∼57-98%; PTX, ∼80-97%). Under physiological conditions (pH 7.4), these NPs exhibited excellent colloidal stability and were capable of protecting drug release, while under acidic conditions (pH 5.5) they showed structural collapse, releasing the therapeutics in an extended manner. Cytotoxicity results demonstrated that the encapsulation in Ac-Dex NPs had a positive effect on the activities of both PPT and PTX against the MCF-7 human breast cancer cell line after 48 h of treatment, as well as toward MDA-MB-231 triple-negative BC cells. PPT/PTX@Ac-Dex NPs were significantly more cytotoxic (IC50/PPT = 0.25-1.77 μM and IC50/PTX = 0.07-0.75 μM) and selective (SI = 2.9-6.7) against MCF-7 cells than all the control therapeutic agents: free PPT (IC50 = 4.57 μM; SI = 1.2), free PTX (IC50 = 0.97 μM; SI = 1.0), the single-drug-loaded Ac-Dex NPs, and the physical mixture of both free drugs. All combinations of PPT and PTX resulted in pronounced synergistic antiproliferative effects in MCF-7 cells, with an optimal molar ratio of PPT to PTX of 2.3:1. PPT/PTX-2@Ac-Dex NPs notably promoted apoptosis, cell cycle arrest at the G2/M, accumulation of intracellular reactive oxygen species (ROS), and combined effects from both PPT and PTX on the microtubule network of MCF-7 cells. Overall, the combination of PTX and PPT in pH-responsive Ac-Dex NPs may offer great potential to improve the therapeutic efficacy, overcome the limitations, and provide effective simultaneous delivery of these therapeutics for BC treatment.

Synthesis, Anti-Cancer Activity, Cell Cycle Arrest, Apoptosis Induction, and Docking Study of Fused Benzo[h]chromeno[2,3-d]pyrimidine on Human Breast Cancer Cell Line MCF-7.

Breast cancer is the predominant form of cancer among women and ranks as the second most prevalent cancer globally, affecting both developed and less developed countries. Presently, accessible cancer treatment methods either employ recently created, secure, and efficient chemotherapeutic medications or directly target innovative pathways that cause apoptosis. One of the indirect strategies for treating this fatal illness has mostly depended on its essential role in cell cycle arrest and apoptosis induction, as well as the antagonistic interaction between the Bcl-2 and Mcl-1 proteins, in order to avert major health repercussions. We reported that newly synthesized fused chromenopyrimidines (3a and 4a) showed potential cell cycle arrest and dual Bcl-2 and Mcl-1 inhibitory characteristics. Bcl-2 and Mcl-1 were the targets of a molecular docking procedure. The previous docking results are in line with the biological data and suggest that 3a may have promising anti-cancer activity.

Exploring the anticancer properties of indole pyrimidine derivatives: Synthesis, structural insights, docking analysis, and in vitro evaluation

The nitrogen containing heterocyclic and chalcones moiety widely recognized as favorable combination of diagnostic and therapeutic facilities in medicinal chemistry. In particular, indole analogs play a very important medicinal role in pharmacology activities, hence, drugs like pindolol, indomethacin, oxypertine, ellipticine, arbidol and ate viridine are well known in market. In this view, the title compounds 4(a-j) were synthesized in good yield. The purified compounds were explained by spectroscopic procedures (FT-IR, 1H NMR, 13CNMR, and LC-MS), and lastly, all synthetic compounds have in-vitro efficacy assessed against the HeLa human cervical cancer and MCF-7 human breast cancer cell lines, and their efficacy was compared to that of the well-known anticancer drug methotrexate (Methotrexate). Compounds 4a, 4b, 4c, and 4e from the series (4a-j) demonstrated the most notable inhibitory activity. The cytotoxicity evaluation of these newly synthesized compounds revealed that 4a, 4b, 4c, and 4e were the most toxic to HeLa cells, with IC50 values for growth inhibition of 20.41 ± 3.14, 23.54 ± 3.27, 24.77 ± 2.14, and 26.10 ± 1.58, respectively. These compounds exhibited an even stronger growth-inhibitory effect on MCF-7 cells, with IC50 values of 18.84 ± 2.69, 19.45 ± 3.14, 22.83 ± 2.68, and 21.80 ± 1.68, respectively. In comparison, methotrexate (Methotrexate) showed IC50 values of 28.29 ± 1.0 for HeLa cells and 45.08 ± 2.61 for MCF-7 cells. Additionally, compounds 4a, 4b, 4c, and 4e played a crucial role in interacting with the catalytic domain of PDE3, demonstrating IC50 values for PDE3A inhibition of 8.05 ± 1.27, 7.55 ± 2.14, 15.09 ± 1.54, and 17.12 ± 3.14, respectively. These results are compared with Cilostazol, a known PDE inhibitor, which exhibited an IC50 of 0.00368 ± 3.14. In-silico studies revealed that compounds (4a, 4b, and 4c) are comparatively very efficient in binding with PDE3A which was further validated with MMGBSA and MDSs.

Thiouracil and triazole conjugate induces autophagy through the downregulation of Wnt/β-catenin signaling pathway in human breast cancer cells.

Autophagy is vital for maintaining cellular homeostasis by breaking down unnecessary organelles and proteins within cells. Its activity varies abnormally in several diseases, including cancer, making it a potential target for therapeutic strategies. The Wnt/β-catenin signaling pathway significantly impacts cancer by stabilizing β-catenin protein and promoting the transcription of its target genes. Therefore, we aimed to identify candidate substances targeting this signaling pathway. We designed and tested a thiouracil conjugate, discovering that TTP-8 had anti-tumor effects on human breast cancer cell lines MCF-7 and MDA-MB231. Our findings showed that TTP-8 upregulated the expression of LC3 protein, a marker of autophagy in breast cancer cells, suggesting that TTP-8 might induce autophagy. Further analysis confirmed an increase in autophagy-related proteins, with consistent results obtained from flow cytometry and confocal microscopy. Interestingly, the induction of LC3 expression by TTP-8 was even more pronounced in MCF-7 and MDA-MB231 cells transfected with β-catenin siRNA. Thus, our research supports the idea that the Wnt/β-catenin signaling pathway influences the regulation of autophagy-related proteins, thereby inducing autophagy. This suggests that TTP-8 could serve as a novel agent for treating breast cancer.

Paclitaxel and Vinblastine Increase Plasminogen Activator Inhibitor-1 Production in Human Breast Cancer MCF-7 Cells but Not MDA-MB-231 Cells.

Cancer chemotherapy increases the risk of thrombosis; however, the mechanisms underlying this thrombosis are not completely understood. Plasminogen activator inhibitor (PAI)-1 is a key molecule in the fibrinolytic system that inhibits tissue plasminogen activator and urokinase, which converts plasminogen into plasmin; therefore, excess PAI-1 increases the risk of thrombosis. In this study, we investigated whether temporary treatment of the human luminal A-type breast cancer cell line MCF-7 with antitumor drugs clinically used for breast cancer therapy promotes PAI-1 production. Treatment of MCF-7 cells with paclitaxel (PTX), a microtubule-stabilizing antitumor drug, at 1 µM for 2 h elevated the PAI-1 concentration of the conditioned medium at 48 h after treatment but not in those treated with tamoxifen and cyclophosphamide. Microtubule assembly inhibitors vinblastine (VBT) and vincristine (VCT) also increased the PAI-1 concentration in the conditioned medium. PAI-1 (SERPINE1) expression was upregulated in MCF-7 cells after PTX, VBT, and VCT treatment; this increase in expression persisted for eight days. In contrast, PAI-1 production in MDA-MB-231 cells treated with PTX, VBT, or VCT did not increase with increasing PAI-1 concentration. This study demonstrated that temporary low-dose treatment with microtubule-associated anticancer drugs increased PAI-1 release from MCF-7 cells but not from MDA-MB-231 cells. These results indicate that chemotherapy against luminal A-type breast cancer using microtubule-associated drugs may cause thrombosis through the inhibition of the fibrinolytic system by PAI-1.

Synthesis, DFT Calculations, and Biological Studies of New 2-Cyano-3-(Naphthalene-1-yl) Acryloyl Amide Analogues as Anticancer Agents.

A set of novel naphthalene derivatives was synthesized via investment of the electrophilic reaction center of the easily obtainable starting substance, 2-cyano-3-(naphthalen-1-yl)acryloyl chloride (1), with various nitrogen nucleophiles and assessed as potential antitumor agents. The chemical structures of these derivatives were completely specified using several spectral and elemental analyses. The antiproliferative efficacy of the discovered compounds against the human cancer cell lines HepG2 and MCF-7 was investigated. Compounds 12b and 9 have more potent anticancer activity versus MCF-7 breast cancer. DFT calculations for the synthesized compounds were studied to determine molecular geometry, frontier orbital analysis, and molecular electrostatic potential. Compound 2 has the lowest energy gap, the highest softness, and the lowest hardness molecule. Also, the electrophilicity values of the studied molecules provide evidence for their biological effectiveness, as compound 9 had significant antiproliferative activity and a high value of electrophilicity (ω) (0.190 eV).

Chemical composition of essential and fixed oils of Tagetes erecta fruits (Iran) and their implications in inhibition of cancer signaling

The current research was conducted to explore, for the first time, Tagetes erecta L. (family Asteraceae) fruits from northwest Iran in terms of the chemical composition of essential and fixed oils, their cytotoxic activities, and the inhibitory effect of essential oil on the PI3K/AKT/mTOR signaling pathway. The volatile oil was obtained through hydrodistillation (Clevenger apparatus). According to gas chromatography–mass spectrometry analysis, the essential oil was rich in cyclic monoterpenoids, 2-isopropyl-5-methyl-3-cyclohexen-1-one (19.99%), d-limonene (12.75%), terpinolene (11.64%) and also the saturated fatty acid palmitic acid (19.09%). Furthermore, the seeds of T. erecta were extracted using hexane by the maceration method. The analysis of fatty acid profile of the fixed oil by gas chromatography-flame ionization detector (GC-FID) demonstrated that the most predominant fatty acids in fixed oil were linoleic acid (59.53%), palmitic acid (13.70%), stearic acid (10.20%), and oleic acid (9.20%). The cytotoxic activity of essential oil, crude oil, and fraction A (obtained from fixed oil) were evaluated by using the MTT assay on MCF7 (human breast cancer cell line), PC3 (human prostate cancer cell line), and U87MG (human glioblastoma cell line). Finally, the effect of essential oil on inhibiting the PI3K/Akt/mTOR signaling pathway was evaluated using real-time PCR. The essential oil exhibited vigorous cytotoxic activity on the U87MG cell line, with an IC50 value of 32.65 μg/mL. Interestingly, the essential oil significantly inhibited the PI3K/AKT/mTOR cascade compared to the non-treated group. Our results suggest that the essential oil holds promise as an anticancer agent for glioblastoma cell lines. To the best of our knowledge, this study is the first to report on the profile of the essential oil of T. erecta fruits and its implications for targeting the PI3K/AKT/mTOR signaling pathway.

Lupeol-3-carbamate Derivatives: Synthesis and Biological Evaluation as Potential Antitumor Agents.

In the following study, a series of new lupeol-3-carbamate derivatives were synthesized, and the structures of all the newly derived compounds were characterized. The new compounds were screened to determine their anti-proliferative activity against human lung cancer cell line A549, human liver cancer cell line HepG2, and human breast cancer cell line MCF-7. Most of the compounds were found to show better anti-proliferative activity in vitro than lupeol. Among them, obvious anti-proliferation activity (IC50 = 5.39~9.43 μM) was exhibited by compound 3i against all three tumor cell lines. In addition, a salt reaction was performed on compound 3k (IC50 = 13.98 μM) and it was observed that the anti-proliferative activity and water solubility of compound 3k·CH3I (IC50 = 3.13 μM), were significantly enhanced subsequent to the salt formation process. The preliminary mechanistic studies demonstrated that apoptosis in HepG2 cells was induced by compound 3k·CH3I through the inhibition of the PI3K/AKT/mTOR pathway. In conclusion, a series of new lupeol-3-carbamate derivatives were synthesized via the structural modification of the C-3 site of lupeol, thus laying a theoretical foundation for the design of this new anticancer drug.

Synthesis of UiO-67 Metal-organic Frameworks (MOFs) and their Application as Antibacterial and Anticancer Materials

This study involved the synthesis of the UiO-67 metal-organic framework; UiO-67 is a well-known type of MOF obtained by coordinating the Zr6O4(OH)4 metal unit with the 4,42-biphenyldicarboxylate organic linker, using the hydrothermal technique. The novelty of the current work is to synthesize UiO-67 MOFs, and their application as biological agents for antibacterial and cancer cells. Subsequently, the composite material UiO-67 was subjected to a comprehensive characterization process involving Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), thermal gravimetric analyses (TGA) and surface area analysis, and the results showed the successful synthesis of the UiO-67 MOFs, with a high specific surface area of 1415 m2/g. The­­­ synthesized UiO-67 for its antibacterial properties tested against five pathogenic bacterial strains, which include three gram-positive and methicillin-resistant pairs including MRSA, S. aureus and Enterococcus faecalis, and Two gram-negative bacteria E. colli and S. typhimurium using the agar well diffusion method. These findings have shown enhanced, strong antibacterial activity against all the five used gram-positive and gram-negative bacterial strains. Furthermore, the anticancer efficacy of UiO-67 was evaluated on two distinct types of cancer cells: We are using MCF-7 (human breast cancer cell line) and HepG2 (human liver cancer cells). The experiments prove that UiO-67 has the potential of cytotoxicity against both Glioblastoma and H460 cancer lines with the ability to inhibit apoptosis at the same time.

Design, Docking, Synthesis, and In vitro Evaluation of Potent Anti-tubercular Agents Targeting DNA Gyrase

Background: Tuberculosis caused by Mycobacterium tuberculosis has been reported to infect about two-third of the global population and to continuously develop multidrug resistance. DNA gyrase, a type II topoisomerase, is a promising target of the quinolone class of drugs in the treatment of tuberculosis. Objective: The present study is focused on the design and synthesis of newer nitrogen heterocyclics containing indole, n-methyl piperazine, piperidine, and pyrrolidine ring structures. Methods: Initially designed compounds were evaluated for their affinity to the DNA gyrase target. The molecular docking performed using FlexX indicated compounds IIb5 (1-(R)-(4-hydroxyphenyl)(4- methylpiperazin-1-yl)methyl)-3-((S)-(4-hydroxyphenyl)(4-methylpiperazin-1-yl)methyl)urea and IIc5 ((1-(R)-(4-hydroxyphenyl)(4-methylpiperazin-1-yl)methyl)-3-((S)-(4-hydroxyphenyl)(4-methylpiperazin- 1-yl)methyl) thiourea to exhibit promising binding affinity (dock score of -15.01 and -13.77) respectively when compared to the reference MFX moxifloxacin (dock score -4.40) with the target 5BS8 (DNA gyrase). Further, the best 10 compounds were synthesized by one-pot synthesis employing the reaction of indole/N-methyl piperazine/piperidine/pyrrolidine with N-substituted benzaldehydes in the presence of acetamide/urea/thiourea to afford the compounds in 54.60% to 85.47% yield. The synthesized compounds were suitably characterized using chromatographic and spectroscopic tools. Results: In the microplate Alamar Blue assay (MABA), compounds IIb1, IIIc2, IIIb1, and IIb5 exhibited good minimum inhibitory concentrations of 1.6 μg/mL, 3.12 μg/mL, and 12.5 μg/mL, respectively, when compared to the standard rifampicin with 0.8 μg/mL inhibitory concentration. The MTB gyrase supercoiling assay performed using Mycobacterium tuberculosis gyrase supercoiling assay kit demonstrated compound IIb5 at a concentration of 300 μg/mL to show gyrase inhibition in comparison to MFX at 60 μg/mL. In the MTT assay performed using the human breast cancer cell line MCF-7, compounds IIc2, IIb5, and IIb1 showed IC50 values of 2.57 μM, 12.54 μM, and 12.75 μM, respectively, compared to doxorubicin (1.10 μM) at 7-48 hrs and 72 hrs of the study. Conclusion: Based on these observations, N-methyl piperazine class of compounds can serve as a lead/pharmacophore for the rational design of potent molecules against MTB gyrase to combat the growing issue of MDR-TB.

Investigating the optical, structural, and therapeutic properties of CuO nanoparticles coated with [BMIM][BF4] Ionic liquid

This work reports a chemical synthesis of 1-butyl-3-methyl imidazolium tetrafluoroborate ionic liquid ([BMIM][BF4] IL) coated copper oxide nanoparticles (CuO-[BMIM][BF4] NPs) by using co-precipitation method. Additionally, bare copper oxide nanoparticles (CuO NPs) are prepared without the addition of the ionic liquid for comparison. Structural morphology and optical properties were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) with selected area electron diffraction (SAED), Fourier transform infrared spectroscopy (FT-IR), ultraviolet–visible spectroscopy (UV–Vis), and photoluminescence spectroscopy (PL). XRD analysis revealed the monoclinic phase of synthesised CuO NPs (with and without addition of IL) with an average crystallite size of 15.3 nm and 8.42 nm for CuO NPs and CuO-[BMIM][BF4] NPs respectively. An examination of the UV–Vis spectra revealed that the optical bandgap decreases with the addition of IL to CuO NPs. Scanning Electron Microscope (SEM) revealed the flake like morphologies in the range of nanoscale. TEM Microscope showed the conventional needle structure of CuO-[BMIM][BF4] NPs. Synthesised NPs showed antimicrobial effects against Streptococcus aureus and Pseudomonas aeruginosa as well as pathogenic fungi, including Aspergillus flavus and Candida albicans, as investigated using the disc diffusion technique. Pseudomonas aeruginosa (bacterial pathogen), Candida albicans (fungal pathogen) were significantly inhibited than the other two organisms. Additionally, the prepared CuO nanoparticles were evaluated for their anticancer properties on MCF7 human breast cancer cell lines using the MTT assay. The results indicated that the synthesised CuO nanoparticles exhibited effective cytotoxicity against MCF7 cells, with an IC50 value of 33.37 μg/mL. These findings are briefly discussed in this manuscript.

Effects of Curcumin and Estrogen Receptor Alpha in Luminal Breast Cancer Cells.

This work examined the potential benefit of curcumin in breast cancer patients as a supplementary drug in ER-positive cancers. The results indicated that in the MCF-7 human breast cancer cell line, E2 and curcumin decreased cell proliferation and the colony-forming capacity and down-regulated protein expression as well as important molecules associated with cell proliferation, such as PCNA and estrogen receptor alpha; genes associated with the epithelial-mesenchymal transition, such as β-catenin, Vimentin, and E-cadherin; and molecules associated with apoptosis. Clinical studies in bioinformatics have indicated a positive correlation between ESR1 and either CCND1 or BCL2 gene expression in all breast cancer patients. Thus, curcumin could become a potential natural adjuvant treatment for patients with estrogen receptor alpha-positive breast cancer and those with resistance or a poor response to endocrine therapy since the reactivation of estrogen receptor alpha is inevitable.

Generating luminescent Graphene quantum Dots from Tryptophan: Fluorosensors for hydrogen peroxide in cancer cells

Herein, we report a single step synthesis of highly fluorescent Graphene Quantum Dots (GQDs) using tryptophan and glycerol as precursors via pyrolysis. The morphological and functional characterization of the prepared GQDs was performed using PXRD, FTIR, TEM, XPS and zeta potential measurements. The prepared GQDs found their practical application in ultrasensitive detection of an emerging potential cancer biomarker, H2O2, by exploiting the fluorescence quenching behaviour of H2O2. To evaluate the detection sensitivity, a series of various concentrations of H2O2 was spiked to biomatrices like, serum and MCF-7 (human breast cancer cell line) cell lysate medium. A remarkably low limit of detection (LOD) was found in serum medium (139.5 pM) which further improved in MCF-7 cell lysate medium (LOD 61.43 pM). Moreover, the sensing capacity of the GQDs was further validated in presence of various physiological variables such as glucose, cholesterol, insulin and nitrite. Sensing assay was also carried out in HaCaT (human keratinocyte cell line) cell lysate medium to compare the performance of our prepared sensor but the non-linearity of the F0/F versus H2O2 concentration plot pointed towards the conduciveness of the MCF-7 cell lysate medium for sensitive detection of H2O2.The mechanism behind the sensing was also explored using spectroscopic methods.

Chemical Composition and Antibacterial, Antioxidant, and Cytotoxic Activities of Essential Oils from Leaves and Stems of Aeschynomene indica L.

The objective of this study was to analyze the chemical composition and evaluate the biological capabilities of the essential oils (EOs) extracted from leaves and stems of wild Aeschynomene indica L. plants by the hydrodistillation method. By using GC-FID/MS, fifty-six and fifty-five compounds, representing 95.1 and 97.6% of the essential oils in the leaves and stems, respectively, were characterized. The predominant constituents of A. indica EOs were (E)-caryophyllene, linalool, viridiflorol, phytol, hexadecanoic acid, trans-verbenol, and α-guaiene. The antibacterial and synergistic activities of the EOs were assessed by microdilution and checkerboard assays. The results revealed a potent inhibition and bactericidal activity against Staphylococcus aureus and Bacillus subtilis with MICs of 0.312-0.625 mg/mL. When combined with traditional antibiotics, the essential oils of A. indica possessed excellent synergistic effects against all tested bacteria. Additionally, the EOs of A. indica leaves showed higher antioxidant activity (IC50 = 0.11 ± 0.01 µg/mL) compared to the stem oil (IC50 = 0.19 ± 0.01 µg/mL) using the ABTS radical scavenging assay. The in vitro cytotoxicity of EOs against human cancer cell lines HepG2, MCF-7, A-549, and HCT-116 was examined, and MTT assays showed that the EOs possessed a significant cytotoxic potential against MCF-7 breast cancer cells, with IC50 values of 10.04 ± 1.82 and 15.89 ± 1.66 μg/mL, and a moderate cytotoxic activity against other tested cells. In conclusion, the A. indica EOs could be considered a potential source of pharmacologically active compounds.

Amino acid deprivation in cancer cells with compensatory autophagy induction increases sensitivity to autophagy inhibitors

ABSTRACT Inhibition of autophagy is an important strategy in cancer therapy. However, prolonged inhibition of certain autophagies in established cancer cells may increase therapeutic resistance, though the underlying mechanisms of its induction and enhancement remain unclear. This study sought to elucidate the mechanisms of therapeutic resistance through repeated autophagy inhibition and amino acid deprivation (AD) in an in vitro model of in vivo chronic nutrient deprivation associated with cancer cell treatment. In the human cervical cancer cell line HeLa and human breast cancer cell line MCF-7, initial extracellular AD induced the immediate expression of endosomal microautophagy (eMI). However, repeated inhibition of eMI with U18666A and extracellular AD induced macroautophagy (MA) to compensate for reduced eMI, simultaneously decreasing cytotoxicity. Here, hyperphosphorylated JNK was transformed into a hypophosphorylated state, suggesting conversion of the cell death signal to a survival signal. In a nutrient medium, cell death could not be induced by MA inhibition. However, since LAT1 inhibitors induce intracellular AD, combining them with MA and eMI inhibitors successfully promoted cell death in resistant cells. Our study identified a novel therapeuic approach for promoting cell death and addressing therapeutic resistance in cancers under autophagy-inhibitor treatment.