Breast Cancer Cell Line MCF-7 Research Articles

Antioxidant And Anticancer Potential of Bioactive Compounds from Locally Isolated Microalgae

The current cancer therapy research focuses on the curative strategies but also targeting to improve the development of the preventive strategies. Anticancer, antibacterial, antioxidant, and anti-inflammatory effects have been demonstrated by the bioactive compound extracted from microalgae. Marine organisms, particularly microalgae might be one the alternative that may contribute to the achievement of one of Sustainable Development Goals (SDG) which is SDG 3, Good Health and Wellbeing. It is crucial for long-term sustainable development to ensure healthy lives and promote well-being at all ages. Two microalgal samples from Malaysia Acutodesmus obliquus (CN01) and Desmodesmus perforates (SP04) were isolated from fresh waters and cultivated. A total of three different solvents, polar, intermediate and nonpolar solvent was used to extracts the microalgae sample which are methanol, acetone and hexane, respectively. Acutodesmus obliquus and Desmodesmus perforates extracts show low total phenolic content in range from 0.2447 ± 0.0009 to 0.2614 ± 0.0003. Secondly, the antioxidants activity of both microalgae shows significant radical scavenging activity especially in acetone extracts of both microalgae, with values of 11.5433 ± 0.0115 and 13.5847 ± 0.0618 for Acutodesmus obliquus (CN01) whereas Desmodesmus (SP04), 13.7898 ± 0.2601 and 22.3212 ± 0.2302 scavenging activity percentage. Then, the anticancer effect of the crude extracts was tested against breast cancer, MCF-7 breast cancer cell lines by using MTT assay and apoptosis assay. Methanolic extract has demonstrated high antiproliferative effect against MCF-7, with cell inhibition percentage within range of 87±1.1271 % to 73 ± 0.2744 % and 82 ± 0.0236 % to 73 ± 0.0423 % of Acutodesmus obliquus (CN01) and Desmodesmus (SP04) respectively. Finally, both microalgae show similar compound group as HPLC is used to identified lipid, which is believed to play the big role in contributing to anticancer and antioxidant activity. This suggests that Acutodesmus obliquus sp and Desmodesmus perforates sp possess diverse biosynthetic capacities, potentially enabling the creation of new pharmaceuticals.

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.

Downregulation of CIAPIN1 regulates the proliferation, migration and glycolysis of breast cancer cells via inhibition of STAT3 pathway

Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) is a protein that regulates apoptosis and programmed cell death. This research aims to evaluate its potential role in inhibiting breast cancer cell proliferation, migration, and glycolysis and uncover its underlying molecular mechanism. We collected breast cancer tissue samples from eight patients between January 2019 and June 2023 in our Hospital to analyse CIAPIN1 expression. We transfected human breast cancer cell lines (MCF7, MDA-MB-231, MDA-MB-453, and MDA-MB-468) with siRNA of CIAPIN1. Finally, we determined protein expression using RT-qPCR and Western blotting. CIAPIN1 expression was elevated in both breast cancer tissue and serum. Overexpression of CIAPIN1 detected in the breast cancer cell lines MCF7 and MDA-MB-468. In addition, CIAPIN1 overexpression increased cell proliferation and migration rate. CIAPIN1 downregulation suppressed cell proliferation while elevated cellular apoptosis, reactive oxygen species (ROS) production and oxidative stress in breast cancer cells. Moreover, CIAPIN1 inhibition remarkably suppressed pyruvate, lactate and adenosine triphosphate (ATP) production and reduced the pyruvate kinase M2 (PKM2) protein expression and phosphorylation of signal transducer and activator of transcription 3 (STAT3) in breast cancer cells. Downregulation of CIAPIN1 suppresses cell proliferation, migration and glycolysis capacity in breast cancer cells by inhibiting the STAT3/PKM2 pathway.

A central composite design-based targeted quercetin nanoliposomal formulation: Optimization and cytotoxic studies on MCF-7 breast cancer cell lines

This study aimed to enhance the efficacy of quercetin (QT) by formulating it into a liposomal drug delivery system utilizing the concept of central composite design. The drug:lipid ratio, cholesterol concentration, and sonication time were selected as independent variables in the study. The vesicle and percentage entrapment efficiency were selected as the dependent variables. Quercetin nanoliposomes (QT-NLs) were prepared via a combination of ethanol injection and thin film hydration. The vesicle size and entrapment efficiency of all formulations were within the ranges of 100 nm and >80 %, respectively. The zeta potential value indicated the stability of the optimized formulation. The contour plots were used to select the desired batch range. SEM studies revealed an imperfect crystalline morphology without any unwanted agglomeration. MTT assays on VERO cell lines indicated the safety of the developed formulation. MTT assays of MCF-7 cells revealed IC50 values of 5.8 μM and 7.9 μM for QT-NLs and QT, respectively. In our study, the optimized formulation exhibited late and early apoptosis and necrosis when used to treat MCF-7 cells. S and G2/M cell cycle phases of MCF-7 cell arrest were confirmed by the cell cycle report. At sub-G0/G1 phase, 2.10 ± 1.1 %; G0/G1 phase, 34.13 ± 1.9 %; S phase, 34.55 ± 0.98 %; and G2/M phase, 26.24 ± 1.7 % of cell arrest were observed. The results demonstrated the effectiveness of the proposed design for the development of corn starch-coated QT-NLs and their activity in breast cancer cell lines.

Green synthesis and anticancer evaluation of dispiroheterocycles containing isatin, tetrahydrobetacarboline, pyrrolidine and aurone motifs

Twenty-one dispiropyrrolidine derivatives were synthesized using a green protocol by the classical [3+2] cycloaddition reaction of aurones with azomethine ylide derived from 1,2,3,4-tetrahydro-β-carboline and isatin. All compounds were well-characterized and out of the twenty-one derivatives, compound 4e, was found to exhibit strongest binding affinity of 8.71 kcal/mol and good stability with PLK1 protein target, which was predicted by molecular docking and molecular dynamic simulation. In vitro studies indicated that the compound exhibited low LC50 value of 4.68 μg/mL on the MCF-7 breast cancer cell lines using MTT assay.

Design, Synthesis and Characterization of Mn(II)Cysteine-Tyrosine Dithiocarbamate Complex for against the Cancer on MCF-7 Breast Cancer Cell Line.

Breast cancer is the most frequently diagnosed cancer and the second cause of death worldwide. The drug often used for chemotherapy is cisplatin. However, the drug cisplatin has a number of problems, including lack of selectivity, undesirable side effects, resistance, and toxicity in the body. So research is carried out on new drug compounds with low toxicity by designing in silico with molecular docking. Mn(II) Cysteine-Tyrosine dithiocarbamate is a new complex molecule whose research involves several steps, such as in-silico molecular docking testing with target proteins, ADMET then synthesis, characterization and in-vitro MCF-7 cells for anticancer drugs. The synthesis process involves the reaction of manganese metal with tyrosine, cysteine, CS2 and KOH. Characterization tests have been carried out including FT-IR spectroscopy, SEM-EDS, UV Vis, conductivity, melting point and XRD. Confirm the structure of the compound using UV Vis, obtained orbitals π to π* and n to π* in the group N = C = S is represented by the absorption at 400 nm and 600 nm, FT-IR with the results obtained by the functional groups O-H, N-H, C =N and C=S. In vitro test results showed morphological changes (apoptosis) in MCF-7 cancer cells starting from 250 μg/mL and an IC50 value of 416.90 µg/mL. Molecular docking studies of the Mn(II)Cysteine-Tyrosine dithiocarbamate complex were identified with 4,4',4''-[(2R)-butane-1,1,2-triyl]triphenol - Estrogen α which showed an active site with amino acid residues GLU323, GLU385, VAL446, ILE514, TRP360, LYS449, MET388, MET357, PHE445, VAL392 and ILE389. Hydrophobic and hydrophobic bonds are seen in Mn(II)Cysteine-Tyrosine dithiocarbamate - Estrogen α has a bond energy of -77.5372 kJ/mol. Despite having a high H-bond interaction intensity, the chemical does not have a powerful enough anticancer impact. Despite the produced compound's low bioactivity, this study should offer important new understandings into how molecular structure affects anticancer activity.

Investigating the Effect of EX-527 as SIRT1 Inhibitor in Breast Cancer Cell Line

Background: Breast cancer is one of the most common malignant and metastatic tumors worldwide that cause death in women. Therefore, preventing the growth and metastasis of cancerous cells is essential for enhancing the prognosis and efficacy of treatment for breast cancer. Sirtuin 1 (SIRT1) is a nicotinamide-adenine dinucleotide (NAD+)-dependent deacetylase that has been linked to a number of biological processes, including genomic stability, cell cycle, cell survival and cancer metastasis. EX-527 is a selective and potent SIRT1 inhibitor. Recent studies have revealed that SIRT1 has an oncogenic role in breast cancer. Objective: To evaluate the effect of EX-527 on the MCF-7 breast cancer cell line. Methods: MCF-7 was cultured in complete DMEM and treated with and without EX-527. Cell viability of the breast cancer cell line was evaluated by MTT assay and apoptosis by Annexin V/PI staining. Migration and invasion of breast cancer cells were determined by wound healing and transwell invasion assays, respectively. Results: Results revealed that EX-527 at a concentration of 25.30 µM was associated with a significant anti-proliferative effect and induction of apoptosis (98.3%) in breast cancer cells. Treatment with EX-527 was also associated with significant suppression of migration and invasion of MCF-7. Conclusions: The current investigation showed that inhibition of SIRT1 by EX-527 inhibits proliferation, migration, invasion and apoptosis of human breast cancer cells.

Improved N-phenylpyrrolamide inhibitors of DNA gyrase as antibacterial agents for high-priority bacterial strains

In this work, we describe an improved series of N-phenylpyrrolamide inhibitors that exhibit potent activity against DNA gyrase and are highly effective against high-priority gram-positive bacteria. The most potent compounds show low nanomolar IC50 values against Escherichia coli DNA gyrase, and in addition, compound 7c also inhibits E. coli topoisomerase IV in the nanomolar concentration range, making it a promising candidate for the development of potent dual inhibitors for these enzymes. All tested compounds show high selectivity towards the human isoform DNA topoisomerase IIα. Compounds 6a, 6d, 6e and 6f show MIC values between 0.031 and 0.0625 μg/mL against vancomycin-intermediate S. aureus (VISA) and Enterococcus faecalis strains. Compound 6g shows an inhibitory effect against the methicillin-resistant S. aureus strain (MRSA) with a MIC of 0.0625 μg/mL and against the E. faecalis strain with a MIC of 0.125 μg/mL. In a time-kill assay, compound 6d showed a dose-dependent bactericidal effect on the MRSA strain and achieved bactericidal activity at 8 × MIC after 8 h. The duration of the post-antibiotic effect (PAE) on the MRSA strain for compound 6d was 2 h, which corresponds to the PAE duration for ciprofloxacin. The compounds were not cytotoxic at effective concentrations, as determined in an MTS assay on the MCF-7 breast cancer cell line.

The Impact of Simultaneous Epigenetic and Epitranscriptomic Intervention in Breast Cancer Cells

Aim: Breast cancer remains a significant cause of mortality worldwide, necessitating the development of innovative therapeutic approaches. Epigenetic and epitranscriptomic regulation have emerged as promising avenues for novel treatments. Sodium Butyrate (NaB) and Meclofenamic Acid (MFA) have gained attention for their respective roles in epigenetic and epitranscriptomic modulation. NaB, a histone deacetylase inhibitor, serves as a critical regulator of chromatin remodeling and gene expression. MFA has been identified to be a potent inhibitor of the FTO enzyme. This inhibitory potential marks its role in epitranscriptomic regulation. This study aimed to investigate the potential effects of MFA and NaB, individually and in combination, on the MCF7 breast cancer cell line. Method: In order to investigate the cytotoxic and apoptotic effects of the combination treatment of MFA and NaB, cell viability assay, Annexin V analysis and Acridine Orange/DAPI staining were executed. Results: The results revealed that the combination treatment unexpectedly exhibited antagonistic effects. This was evidenced by a remarkable increase in cell viability and a decreased apoptotic response compared to individual treatments. The strongest antagonistic effect was observed when the cells were treated with 100 μM MFA and 2 mM NaB for a period of 48 hours (CI = 88.3). Conclusion: This study, for the first time, sheds light on the complex interaction between meclofenamic acid and sodium butyrate that reveals an unexpected antagonistic effect on MCF7 breast cancer cells. These findings challenge conventional concepts of synergistic interactions and underscore the complexity of drug combinations in breast cancer treatment.

Biosynthesis of Naringenin@Cu (II), Zn (II) Hybrid Nanoflower: Anticancer Activity Assay process

In the study, the synthesis of organic-inorganic hybrid nanoflowers, which have a flower-like structure and are called nanoflowers, was carried out. For this purpose, hybrid nanoflower synthesis was carried out using naringenin as the organic part and different metal ions (Cu and Zn) as the inorganic part. Various analyzes were carried out to characterize the synthesized nanoflowers (such as SEM, EDX, FTIR, XRD). In addition, the anticancer activities of hybrid nanoflowers were tested on the MCF7 (breast cancer) cell line. It was concluded that there was a good increase in anticancer activity when naringenin was converted into hybrid nanoflower form. In particular, the anticancer activity of hybrid nanoflowers synthesized with Zn metal ion was quite excellent. This means that Zn hybrid nanoflowers may be a safer therapeutic alternative than others.

Mechanically Flexible Self-Healing Mg(II)-Metallogel: Approach of Triggering the ROS-Induced Apoptosis in Human Breast Cancer Cells.

A self-assembly-directed thixotropic metallohydrogel (i.e., Mg-Tetrakis) of Mg(II)-metal salt and N,N,N',N'-tetrakis(2-hydroxy-ethyl)ethylenediamine (i.e., Tetrakis) was successfully achieved. The organic chemical component N,N,N',N'-tetrakis(2-hydroxy-ethyl)ethylenediamine was used as a low-molecular-weight gelator, and water was employed as the gel-forming solvent. The fabricated supramolecular metallohydrogel promisingly depicted viscoelastic and mechanoelastic behaviors, which are interpreted through various rheological parameters. The thixotropic behavior of the metallohydrogel is also well characterized through this rheological study. Field emission scanning electron microscopy microstructural analyses were performed to visualize the morphological arrangements of the metallohydrogel. The anticancer properties of the synthesized metallogels are investigated through this work. The cytotoxic potential of the metallohydrogel on the MCF-7 breast cancer cell line is critically examined. Reducing the growth of breast cancer cell line MCF-7 through the treatment of gel on the colony formation assay has been explored through the work. The antimigratory potential of the metallohydrogel on the MCF-7 cell was also scrutinized. The anticancer effect of the fabricated metallohydrogel is inspected through various assay formation strategies, like wound healing assay, tumor spheroid inhibition assay, nuclear fragmentation assay, and so on. Quantitative reactive oxygen species analysis of the cancer cells by treatment with the metallohydrogel was also conducted through this study. The mechanistic apoptosis study was executed by studying the expression of various apoptotic markers like BAX, BCL2, PUMA, and NOXA.

Efficacy of Qi-Gen powder for immunity enhancement and investigation of its therapeutic mechanisms through gene expression profiling

Infection with different viruses threatens the health of animals in the livestock and poultry industry. Immunopotentiators can increase natural immunity and vaccination efficacy; however, most are expensive chemical and biological compounds with questionable safety. Traditional Chinese medicines (TCMs) such as Yupingfeng (YPF), a well-known immunomodulatory remedy, provide healthy alternatives to such agents. The aim of this study was to examine the therapeutic properties of Qi-Gen powder (QG) and compare them with those of YPF. The immune organ index, cytokine levels, and other indicators were utilized to evaluate the effects of QG in an immunosuppression mouse model. QG was further assessed for its ability to enhance vaccine effectiveness in chickens immunized for Newcastle disease virus (NDV). Potential therapeutic mechanisms and targets of QG were examined in the breast cancer cell line MCF-7 using microarray technology combined with the TCM systems pharmacology database of known targets. Compared with model controls, QG improved immunological function, outperforming YPF in mice. QG also enhanced the immunological response to NDV vaccine in immune organs and increased feed intake of chickens. Further research is needed to validate the link between the PI3K/Akt/GSK-3 pathway and the immune-boosting effects of QG.

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.

Anticancer, antimicrobial and antioxidant activity of CuO–ZnO bimetallic nanoparticles: green synthesised from Eryngium foetidum leaf extract

In the present study, green synthetic pathway was adapted to synthesize CuO–ZnO bimetallic nanoparticles (BNPs) using Eryngium foetidum leaf extract and their anti-cancer activity against MCF7 breast cancer cell lines, anti-microbial activity and in vitro anti-oxidant activity were evaluated. Various bio-active compounds present in leaf extract were responsible for the reduction of CuO–ZnO NPs from respective Cu2+ and Zn2+ metal precursors. In the present study, the involvement of bio-active compounds present in E. foetidum extract before and after green synthesis of BNPs were evaluated for the first time. Rod-shaped and spherical structural morphology of synthesized BNPs were revealed by using FESEM, TEM, and XRD analysis with particle size ranged from 7 to 23 nm with an average size of 16.49 nm. The distribution of Cu and Zn were confirmed by elemental mapping. The green synthesized CuO–ZnO NPs showed significant cytotoxic effect with the inhibition rate 89.20 ± 0.03% at concentration of 500 μg/mL. Again, good antioxidant activity with IC50; 0.253 mg/mL and antimicrobial activity of BNPs were also evaluated with the increasing order of MIC; E. coli (7.81 μg/mL) < B. subtilis (62.5 μg/mL) < S. aureus (31.25 μg/mL).

Anticancer Activity of Benzo[a]phenoxazine Compounds Promoting Lysosomal Dysfunction.

Specific cancer therapy remains a problem to be solved. Breast and colorectal cancer are among the cancers with the highest prevalence and mortality rates. Although there are some therapeutic options, there are still few effective agents for those cancers, which constitutes a clinical problem that requires further research efforts. Lysosomes play an important role in cancer cells' survival, and targeting lysosomes has gained increased interest. In recent years, our team has been synthetizing and testing novel benzo[a]phenoxazine derivatives, as they have been shown to possess potent pharmacological activities. Here, we investigated the anticancer activity of three of the most potent derivatives from our library, C9, A36, and A42, on colorectal- and breast-cancer-derived cell lines, and compared this with the effect on non-neoplastic cell lines. We observed that the three compounds were selective for the cancer cells, namely the RKO colorectal cancer cell line and the MCF7 breast cancer cell line. In both models, the compounds reduced cell proliferation, cell survival, and cell migration, accumulated on the lysosome, and induced cell death accompanied by lysosomal membrane permeabilization (LMP), increasing the intracellular pH and ROS accumulation. Our results demonstrated that these compounds specifically target lysosomes from cancer cells, making them promising candidates as LMP inducers for cancer therapy.

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.

Novel coumarin-6-sulfonamide-chalcone hybrids as glutathione transferase P1-1 inhibitors.

Multidrug resistance (MDR) mechanisms in cancer cells are greatly influenced by glutathione transferase P1-1 (hGSTP1-1). The use of synthetic or natural compounds as hGSTP1-1 inhibitors is considered an effective approach to overcome MDR. Nine compounds consisting of coumarin-6-sulfonamide linked to chalcone derivatives were synthesized and evaluated for their ability to inhibit hGSTP1-1. Among the synthetic derivatives, compounds 5g, 5f, and 5a displayed the most potent inhibitory effect, with IC50 values of 12.2 ± 0.5 μΜ, 12.7 ± 0.7 and 16.3 ± 0.6, respectively. Kinetic inhibition analysis of the most potent molecule, 5g, showed that it behaves as a mixed-type inhibitor of the target enzyme. An in vitro cytotoxicity assessment of 5a, 5f, and 5g against the human prostate cancer cell lines DU-145 and PC3, as well as the breast cancer cell line MCF-7, demonstrated that compound 5g exhibited the most pronounced cytotoxic effect on all tested cell lines. Molecular docking studies were performed to predict the structural and molecular determinants of 5g, 5f, and 5a binding to hGSTP1-1. In agreement with the experimental data, the results revealed that 5g exhibited the lowest docking score among the three studied inhibitors as a consequence of shape complementarity, governed by van der Waals, hydrogen bonds and a π-π stacking interaction. These findings suggest that coumarin-chalcone hybrids offer new perspectives for the development of safe and efficient natural product-based sensitizers that can target hGSTP1-1 for anticancer purposes.

The effects of conjugating anti-MUC1 aptamers on gold nanobipyramids and nanostars for photothermal cancer ablation.

Aim: To ascertain the impact of shape and surface modification of anisotropic nanoparticles on the toxicity and photothermal efficiency toward cancerous cell lines.Methods: Gold nanobipyramids and nanostars surface modified with MUC1 aptamer were used in the current study to explore the toxicity and photothermal efficiency on MCF7 breast cancer cell lines via MTT assay.Results: Surface functionalization with MUC1 aptamer showed significant reduction in % cytotoxicity and increase in % specific internalization of nanostructures into MCF7 cell lines. Further, the photothermal studies accomplished at IC50 concentration for 6h of treatment and laser exposure for 15min reported that aptamer-conjugated nanobipyramids were more effective and specific toward MCF7 cell lines than aptamer-conjugated nanostars.Conclusion: This work establishes a platform for the development of tailored photoablation based gold nanostructures for in vivo studies.

Potential of Soursop Leaf Extract as an Antioxidant in MCF-7 Cells

The frequency of breast cancer tends to increase. Malondialdehyde (MDA) is a marker of oxidative stress as an end product from the chain reaction of lipid peroxidation. The use of traditional medicine soursopleaf (Annona muricata L.) has been reported for a long time because of its bioactivity as an antioxidant. This study analyzes the relationship between MDA levels and glutathione enzymes in MCF-7 cells given the methanol extract of soursop leaves. The methanol extract of soursop leaves was carried out by infusion method. The methanol extract of soursop leaves was given to cancer cells at several doses with an incubation of 24 hours. The cytotoxic test was carried out using the MTT method. Measurement of MDA levels was carried out using the thiobarbituric acid reactive substance (TBARS/TBA) reactivity test method. GSH measurements used the colorimetric method. The results showed that the ethanol extracts of soursop leaves have cytotoxic activity in the MCF-7 breast cancer cell line with IC50 values of 23.96 ppm. Ethanol extract of soursop leaves increased levels of MDA inhibition and GSH level. Soursop leaf extract could increase MDA inhibition GSH level in human breast cancer cells MCF-7.