MCF-7 Cell Lines Research Articles

Coptisine enhances the sensitivity of chemoresistant breast cancer cells by inhibiting the function and expression of ABC transporters

BackgroundMultidrug resistance (MDR), mainly caused by ATP-binding cassette transporters (ABCTs) efflux, makes it difficult for many anticancer drugs to treat breast cancer (BC). Phytochemicals can reverse cancer’s MDR by modifying ABC transporter expression and function, as well as working synergistically with anticancer drugs to target other molecules. The reversal effect of the isoquinoline alkaloid coptisine (COP) was assessed on four breast cell lines; Two sensitive MCF-7 cell lines with positive estrogen, androgen, progesterone, and glucocorticoid receptors, as well as MDB-MB-231 cells with negative estrogen, progesterone, and HER2 receptors, and two doxorubicin-resistant cell lines, MCF-7/ADR and MDB-MB-231/ADR.MethodsThe cytotoxicity of COP and its ability to improve doxorubicin (DOX) cytotoxicity were assessed using the MTT assay. The effectiveness of COP in reversing DOX resistance was evaluated by calculating resistance ratio (RR) values, combination index (CI), and isobologram (IB). The inhibitory effect of COP on ABCT efflux function in comparison to verapamil (VER) was evaluated by measuring the cellular accumulation of Rho123 using flow cytometry. The impact of COP, either alone or in combination with DOX, on the gene expression of ABCTs (P-gp/MDR1, BCRP, and MRP1) of investigated cell lines was assessed by RT-PCR.ResultsThe COP showed modest cytotoxicity on the examined cell lines. In MCF-7/ADR and MDA-MB-231/ADR cells, COP (31 μM) enhanced DOX cytotoxicity with CI (0.77 and 0.75), RR (2.58 and 3.33), and IB suggesting synergism. COP significantly inhibits ABCT function in resistant BC cell lines, increases Rho123 accumulation, and decreases efflux more than VER; 2.1 and 1.2-fold, respectively. The combination of COP and DOX had a strong inhibitory effect on ABCT function (3.1 and 3.9 times VER, P< 0.001) and downregulated the genes and protein expression of ABCT.ConclusionCOP reversed ABCT-mediated multidrug resistance in vitro, indicating its potential as a multidrug resistance-reversing agent in cancer chemotherapy.

Biosynthesis of ZnO nanocomposites from Mentha spicata applications of antioxidant, antimicrobial and genotoxicity advances in MCF-7 cell line

This study focuses on enhancing the, Spearmint (Mentha spicata), an aromatic herb indigenous to Europe and Asia, which is valued for its refreshing flavor and potential health benefits. This herb is widely utilized in culinary practices, medicinal applications, and cosmetic formulations. The ethanol extract derived from the M. spicata leaf contains is rich secondary metabolites with various bioactive properties: Specifically, such as tannins, flavonoids, and polyphenols are known for their antioxidant and anti-inflammatory effects, saponins help reduce cholesterol, and alkaloids have analgesic properties. The extract has a total flavonoid content (TFC) of 231.37 ± 2.05 mg GAE/g and a total phenol content (TPC) of 247.32 ± 5.07 mg GAE/g. Zinc oxide (ZnO) nanoparticles were synthesized from this extract and subsequently characterized through various analytical techniques. The absorbance measurement at 437 nm confirmed the successful nanoparticle synthesis. FTIR spectra showed water-related absorption bands at 3330 cm−1 and 3337 cm−1. Scanning electron microscopy (SEM) indicated the presence of spherical nanoparticles of about 25.4 nm, while transmission electron microscopy (TEM) illustrated particles ranging from 20 to 50 nm with high crystallinity and a lattice spacing of 0.297 nm. X-ray diffraction (XRD) analysis confirmed their crystalline structure with distinct Bragg reflections at 39.1°, 46.1°, 68.7°, and 79.2°, which corresponding to (111), (200), (220,311) planes, respectively (JCPDS card no. 01–080-1876). Energy-dispersive X-ray spectroscopy (EDX) confirmed the high purity of the synthesized ZnO nanocrystals. The nanoparticles demonstrated significant antioxidant activity with radical scavenging rates up to 97.33 %, effective antimicrobial properties, and notable anticancer activity, achieving 99.75 % inhibition of MCF-7 cells at 40 μg/mL. These findings highlight the nanoparticles' potential applications in health and medicine.

Development of Wheatgrass (Triticum aestivum) Extract Loaded Solid Lipid Nanoparticles using Central Composite Design and its Characterization- Its In-vitro Anti-cancer Activity

Background: The prevalence of cancer is around the world and is identified as a multifactorial ailment. One of the most common causes of cancer in the world is oxidative stress, and this can be overcome by taking herbal plant wheatgrass in any form. As colloidal carriers with particle sizes of 50-1,000nm, Solid Lipid Nanoparticles (SLNs) combine the benefits of liposomes, emulsions, and other colloidal systems to deliver drugs at their targets. Objective: Aim and objective of the present work is to formulate wheatgrass extract loaded solid lipid nanoparticles using Central Composite design and to investigate the effect of formulation variables. Using hot homoginization method, the present work aimed to formulate wheatgrass loaded chitosan solid lipid nanoparticles using central composite design and to evaluate the extract potential to treat breast cancer on MCF-7 cell line. Methods: This study investigated the effect of three formulation variables on particle size, namely the sodium alginate concentration, the calcium carbonate concentration, and the homogination time. Extraction of wheatgrass was done in soxhlet extractor, using methanolic extract. The hot homogenization technique was used to prepare Triticum aestivum extract loaded solid lipid nanoparticles (SLNs). Result: For CCD, all formulations were analyzed for particle size, which ranged from 362.5 to 933.8 nm, and for polydispersity index, which ranged from 0.137 to 5.799. Batch code SLN-6 was found to be finest suitable because of maximum loading capacity of 67.76 ±0.17 % (w/w), maximum entrapment efficiency of 65.81 ± 0.11 % (w/w) and minimum particle size of 362.5nm by using sodium alginate as surface stabilizer at homogenization time ~ 5 min and having maximum percentage yield of 43.66%. Conclusion: During characterization studies and MCF-6 cell line studies, it was found that batch code SLN-6 was found to be finest suitable and wheatgrass has anti-oxidant potential, and potent against breast cancer.

Hansen parameters and GastroPlus assisted optimized topical elastic liposomes to treat breast cancer using a novel isatin derivative

Breast cancer treatment is a global health challenge using conventional toxic chemotherapeutic agents. A novel isatin could be a promising alternative. An isatin derivative (TM-19) was synthesized and characterized using NMR (nuclear magnetic resonance), mass spectrometry, Fourier transform infrared (FTIR), and differential scanning calorimetry (DSC). HSPiP and GastroPlus predictive software were used to predict suitable solvents for solubility and in vivo oral pharmacokinetics in humans (fasted condition), respectively. Based on predictive findings, topical elastic liposomes (phosphatidylcholine as PC and span 80 by film hydration method) was prepared, characterized, and optimized using QbD (quality by design). QbD identified the impact of composition on response variables (Y1 for size, Y2 for polydispersity index, Y3 for zeta potential, and Y4 for %EE). In vitro cytotoxicity study was carried out against MCF-7 cell lines. Low molecular weight and lipophilic TM-19 was crystalline in nature (255 g/mol). GastroPlus program predicted limited in vivo dissolution and poor oral absorption (10.4 %). Results confirmed the highest TM-19 solubility in DMSO (dimethyl sulfoxide) ˃ chloroform ˃ PEG 400 (polyethylene glycol 400). Considering experimental and predicted data, topical delivery of TM-19 using optimized (desirability parameter value = 0.97) elastic liposomes (TF1) was quite promising due to optimal size (344 nm), high %EE (61.7 %), low PDI (0.45), and optimal zeta potential (− 12.34 mV). TM-19 loaded TF1 elicited concentration dependent cytotoxic effect (˃ 90 % at 10 µM) against MCF-7 as compared to TM-19 suspension.

Design, Synthesis, Computational Studies and Evaluation of Novel 2, 4, 5-Trisubstituted Pyrimidine Derivatives for Anticancer Activity against MCF-7 and A549 Cell Lines

Synthesized novel trisubstituted pyrimidine derivatives (U 01-15) were tested for anti-cancer efficacy against two cancer cell line MCF-7 and A549. Several spectroscopic methods assisted to characterized and confirmed all synthesized compounds. Some of the synthesized pyrimidine derivatives showed strong effectiveness, with IC50 values comparable to the standard drug doxorubicin and gefitinib. Compounds U-02, U-04, U-07, U-10 and U-11 showed good anti-cancer activity for both cell lines having IC50 values in range from 12.06 µM to 22.45 µM, while compounds U-06 and U-03 showed moderate potency against both the cell lines, respectively. Using PyRx software (based on Auto Dock 4 and a genetic algorithm), all the synthesized compounds were put through a molecular docking with receptor tyrosine-protein kinase erbB-4 and docking score was compared to approved drugs, gefitinib and lapatinib. Interestingly almost all derivatives showed good docking score as compared to reference drugs. Molecular dynamics simulation of the U-11 protein-ligand complex over 100 ns revealed key insights into stability and conformational changes. RMSD analysis indicated stability between 10-20 ns with fluctuations up to 5.71 Å, while RMSF showed an average fluctuation of 1.74 Å, particularly in the loop regions. Molecular interactions, including hydrogen bonds, were observed with key residues such as ASP836, MET774, and LEU769.Future studies could focus on optimizing the most promising pyrimidine derivatives, such as U-02, U-04, U-07, U-10, and U-11, for enhanced potency and selectivity through advanced biological testing and structure-activity relationship studies may provide deeper insights into their therapeutic potential against cancer.

Design, synthesis, structural characterization, cytotoxicity and computational studies of Usnic acid derivative as potential anti-breast cancer agent against MCF7 and T47D cell lines

Development of novel inhibitors is necessary to counteract the rising prevalence of breast cancer (BC) in women in recent years, as evidenced by the side-effect profiles of a few clinically approved inhibitors. In this study, the usnic acid derivative (UA1) was synthesized due to the effectiveness of usnic acid (UA) against BC cell line. Furthermore, the structure of synthesized compound was determined using FT-IR, 1H-NMR, 13C-NMR, HSQC, and HMBC spectroscopic techniques. The anticancer potential of UA1 was assessed using the MTT assay on two different cell lines of BC including MCF7 and T47D. To ascertain the binding affinity and stability of the docking complex, further procedures included the in silico molecular docking, molecular dynamic simulation, principal component analysis, and binding free energy experiments. The cytotoxicity results show that the UA1 exhibits strong antitumor activities and comparable effects against BC cell lines with the IC50 values of 9.21µM for MCF7 cell and 14.8µM for T47D cell, respectively, where the positive control cisplatin showed the IC50 values of 8.95µM for MCF7 cell and 10.9µM for T47D cell. Additionally, the molecular docking results of UA1 showed that it interacts strongly into the active site of target protein. Molecular dynamics simulation results also revealed that the docking complex was formed stability with the RMSD and RMSF values of 0.50nm and 0.19nm, respectively. According to the PCA analysis, the target protein displays good conformational space behaviour when bound with UA1. Furthermore, the UA1 showed the free binding energy value of -18.52kcal/mol with the target protein, which indicating that UA1 may prevent BC.

Synthesis, structural elucidation, ion flotation and biological evaluation of Ni(II) and Zn(II) Complexes featuring a heterocyclic thiosemicarbazide ligand with their computational studies

Herein, Ni(II) and Zn(II) complexes were synthesized using the heterocyclic thiosemicarbazide ligand (Z)-N-(2-oxoindolin-3-ylidene)nicotinohydrazide (H2L). The structures and geometries of these complexes were identified using elemental analysis, FT-IR, UV-Visible, Mass spectroscopy and thermogravimetric analysis (TGA). These techniques confirmed the composition of the target chelates as [Ni₂(HL)₂Cl₂(H₂O)₄].3H₂O with an octahedral geometry and [Zn(HL)(OAc)(H₂O)] with a tetrahedral geometry. Conductivity measurements indicated the non-ionic nature of the complexes. Moreover, the chelation patterns, structural configurations, and molecular interactions within the complexes were further corroborated through quantum mechanical computations, specifically density functional theory (DFT).An ion flotation method was employed to investigate the removal of nickel and zinc ions from aqueous solutions. This approach involved the formation of a complex between Ni(II) or Zn(II) ions and H₂L, followed by flotation using oleic acid (HOL) as the surfactant. Various parameters, including pH, surfactant and metal ion concentrations, the presence of foreign ions, and temperature, were systematically tested to determine the optimal flotation conditions. Furthermore, the compounds were evaluated for their effects on human carcinoma cells and their antibacterial properties. Additionally, molecular docking studies of the ligand, H₂L and its complexes were performed using the XP Glide module within the Schrödinger suite, targeting HepG2 (PDB ID: 2OH4) and MCF-7 (PDB ID: 3W2S) cell lines.

Ionic Liquid Catalyzed Microwave Assisted Synthesis, Characterization and Anticancer Activity of Novel Pyrazolo[3,4-d]pyrimidine Derivatives

A rapid and efficient method has been developed for the synthesis of pyrazolo[3,4-d]pyrimidines (5a-j) via microwave assisted method as well as conventional method using four components system in the presence of ionic liquid 2-methyl-imidazolium thiocyanate as a green catalyst. It was found that ionic liquid showed better reactivity than p-toluene-sulfonic acid (p-TSA) and L-proline. All the synthesized pyrazolo-pyrimidine derivatives were characterized by FT-IR, 1H NMR, 13C NMR spectral and elemental analysis. Further, the in vitro anti-breast cancer activity was evaluated by performing cytotoxicity studies against MCF-7 cell lines at different concentrations of synthesized compounds ranging from 100 to 500 µg/mL. Among the series of compounds, compounds 5a and 5d showed significant cytotoxic effect at the lowest concentration. However, all the synthesized compounds proved to be efficient against inhibiting breast cancer cells.

Synthesis, characterization, cytotoxic activity, and molecular docking of 3,4-diaminobenzophenone-CuhNFs and its major components-based nanoflowers

In this study, organic–inorganic hybrid nanoflower (hNFs) synthesis was realized using 3,4-diaminobenzophenone and Cu(II) metal ions as organic and inorganic ingredients, respectively. The characterization of the synthesized hNFs was carried out using SEM, EDX, FT-IR, XRD, and elemental mapping. The cytotoxic effect of hNFs was investigated against A549 (lung) and MCF-7 (breast) cancer cell lines. Interactions of 3,4-diaminobenzophenone were also investigated via molecular docking studies at the binding site of the human estrogen receptor (PDB ID:3ERT) and epidermal growth factor receptor tyrosine kinase (PDB ID: 1M17). Physicochemical and pharmacokinetic parameters for ligands that could be potential anticancer drug candidates were determined by ADME prediction calculations from in silico approaches. In vitro results showed an increase in cell death when the synthesized hybrid nanoflowers were applied against both cell lines, depending on the concentrations tested. Additionally, it was determined that the synthesized nanoflower was more effective on the MCF-7 cell line.

Anticancer Potential of some Plants of Mythological Importance

Background: Cancer is considered one of the leading causes of death internationally, accounting for nearly 10 million deaths in 2020. It was reported that between 30 and 50% of cancers may be prevented by warding off risk factors and imposing existing proof-based prevention techniques. The cancer burden can also be reduced through early detection of cancer and appropriate remedies and care for patients who develop most cancers. Objective: The objective of the research work is to check out the importance of shortlisted medicinal plants of mythological importance in cancer management. Methods: Michelia champaca and Elaeocarpus ganitrus have been obtained from the BBD Group campus and NBRI Garden, Lucknow, and authenticated by CSIR Institute NISCAIR (Raw Material & Herbarium Division), New Delhi. Extraction was performed by use of a warm system known as the Soxhlet extraction method with the utilization of hydroalcoholic solvent, and the plants were further studied for their anticancer activity in various cancer cell lines, including MCF-7, HeLa, and HepG2 cell lines. Results: Phytonutrients are found in both shortlisted plants; Elaeocarpus ganitrus and Michelia champaca are responsible for their medicinal importance. Both medicinal plants have been investigated for anticancer activity, and it was found that both plants have the capacity to reduce the proliferation rate and also induce apoptosis of cancer cells. Conclusion: Phytochemical analysis of Elaeocarpus ganitrus and Michelia champaca (leaves) extracts were found to have alkaloids, flavonoid content material, phenolic compounds, and many others., and exceptional antioxidant properties. Ultimately, Elaeocarpus ganitrus and Michelia champaca have a satisfactory capacity to supply pure antioxidants for livestock, and further relevant research along these lines would be profitable.

Construction of Isochromanones via Hemin-Catalyzed Phenol-Enamine Oxidative Annulation.

We have developed a hemin-catalyzed biomimetic oxidative annulation of 2,3-dihydroxybenzoic acid with an array of cyclic enamines to form isochromanones in good to excellent yields and high regioselectivity. This formal [4+2] cycloaddition protocol showed high efficiency and remarkable functional group tolerance. Mechanistic studies indicate the involvement of a single-electron oxidation pathway. Preliminary biological investigations showed that isochromanones 3ag and 3ca exhibited antineoplastic activities against MCF-7 cell lines with IC50 values of 25.21 and 29.09 μM, respectively.

Therapeutic Potential of Rare Sesterterpenoids from Aspergillus Variecolor Strain SDG and Docking Studies.

Ethyl acetate extract of the cultures of the soil-derived filamentous fungus, Aspergillus variecolor SDG strain from Nallamala forest resulted in the isolation of extremely rare sesterterpenoids, stellatic acid (1) and andilesin C (2). We report a thorough chemical characterization of these compounds using various spectroscopic techniques and evaluation of their in vitro preclinical therapeutic potential. Stellatic acid exhibits potent antioxidant activity with an IC50 of 38 μg/mL and significant anticancer activity against HeLa, HepG2, MCF7, and A549 cancer cell lines with an IC50 of 7-12 μM. On the other hand, andilesin C displayed moderate cytotoxicity against DU145 and B16F10 cancer cell lines but lacked antioxidant activity. Furthermore, the potential hypoglycemic property of stellatic acid was evaluated by measuring its inhibitory effect against α-glucosidase. It exhibited tenfold potency against yeast α-glucosidase (IC50 101.73 μg/mL) than mammalian α-glucosidase (IC50 1000.00 μg/mL). Docking studies were also performed to suggest the interaction mode of stellatic acid in the α-glucosidase enzyme active site. Notably, yeast α-glucosidase shows a higher affinity towards stellatic acid than mammalian α-glucosidase (3TOP). Thus, the in vitro preclinical study of stellatic acid suggests its potential efficacy in therapeutic drug development.

Nanocochleate-based delivery of quercetin with enhanced therapeutic potential: formulation, cytotoxicity and pharmacokinetics study

BackgroundQuercetin has well-proven anticancer potential through various mechanisms, but its applications in drug delivery are limited due to poor biopharmaceutical properties. The present study was aimed to formulate quercetin nanocochleates (QNC) in order to overcome these limitations. QNC formulation was fabricated by a trapping method, optimized and evaluated for various formulation aspects, in vitro cytotoxicity and pharmacokinetic parameters.ResultDeveloped nanocochleates possess particle size and encapsulation efficiency of 205.6 ± 2.55 nm and 76.36 ± 0.88%, respectively. In vitro cytotoxicity study performed using MCF-7 cell lines revealed the comparative efficiency of QNC over pure quercetin. Total growth inhibition concentration (TGI) for pure quercetin was 96.73 μg/ml, while for QNC it was 83.29 μg/ml. Pharmacokinetic study results showed improvement in Cmax and AUC after QNC formulation with increased Tmax showing sustained release.ConclusionOverall, the developed QNC formulation markedly improved cytotoxic potential and biopharmaceutical aspects.

Cytotoxic activity of water and ethanol extract of Curcuma caesia (black turmeric) on breast cancer cell line

Breast cancer is one of the cancers with the highest incidence and mortality rate in the world. Curcuma caesia (Black turmeric) is known to have neuroprotective, anthelmintic, sunscreen activity, anti-diabetic and also anti-cancer activity. This study aimed to determine the phytochemical content and possible cytotoxic activity of C. caesia water extract (EWCC) and C. caesia ethanol extract (EECC) on breast cancer cell lines. Samples were extracted using two extraction methods, maceration technique using 96% ethanol as solvent and double boiling using water as a solvent. The phytochemical content, total phenolic content (TPC), and total flavonoid content (TFC) of each extract were determined using spectrophotometer method. Cytotoxic activity was measured using MTT assay on MCF-7 and 4T1 breast cancer cell lines (24 hrs and 48 hrs). Results showed that EWCC and EECC contained flavonoids, alkaloids, and polyphenols. The values of TPC and TFC were 106.08 mg GAE/100 g and 4.32 mg QUE/g for EECC, respectively, and 73.29 mg GAE/100 g and 3.40 mg QUE/g for EECC, respectively. Meanwhile, the cytotoxic activity test found that EWCC did not provide cytotoxic activity on MCF-7 and 4T1 cells. In the MCF-7 cell line, EECC exhibited IC50 values of 212.90 µg/mL at 24 hrs and 311.91 µg/mL at 48 hrs. Similarly, in the 4T1 cell line, EECC exhibited IC50 values of 161.06 µg/mL at 24 hrs and 150.89 µg/mL at 48 hrs. From these results, it can be concluded that EECC has cytotoxic activity in MCF-7 and 4T1 breast cancer cell models, so this extract can be studied more deeply to determine its pathway of action.

Anti-Inflammatory and Anti-proliferative Role of Essential Oil of Leaves of Cleistocalyx operculatus (Roxb.) Merr. & Perry.

Phytochemicals have long remained an essential component of the traditional medicine system worldwide. Advancement of research in phytochemicals has led to the identification of novel constituents and metabolites from phytochemicals, performing various vital functions ranging from antimicrobial properties to anticarcinogenic roles. This plant is traditionally used by local people to manage inflammation. In this study, we aim to extract and chemically profile the essential oil from the leaves of Cleistocalyx operculatus (Roxb.) Merr. & Perry and study of the anti-inflammatory and anti-proliferative role of essential oil. The hydro distillation method was used for the extraction of essential oil, and the GC-MS was applied for the chemical profiling. The percentage of cell viability was calculated using a crystal violet assay, colony formation assay was performed using Semiquantitative PCR, Propodium iodite staining was used for cell death assay, and Western blotting was used to determine antibodies and proteins. Schrodinger 2015 software was used for molecular docking. Myrcene, a monoterpene, constitutes 56% of the oil and could be attributed to its anti-inflammatory potential. Treatment of LPS-challenged mouse macrophages RAW264.7 cells with essential oil resulted in a decline in the inflammatory markers, such as IL-1β, TNFα, iNOS, COX-2, and NFκB. Further, essential oil inhibited cancer PC-3, A431, A549, and MCF-7 cell lines at concentrations lower than normal PNT2 and HEK-293 cell lines. This decline in proliferative potential can be attributed to a decline in anti-apoptotic proteins, such as procaspase 3 and PARP, an increase in CKIs, such as p21, and a decline in the Akt signaling responsible for survival. The essential oil of the plant Cleistocalyx operculatus may be a potential lead for anti-inflammatory and anti-proliferative function.

Phosphazene Tripeptide Conjugates: Design, Synthesis, In Vitro Cytotoxicity and Genotoxicity, Molecular Interactions in Binding Pockets on Human Breast and Colon Cancer Cell Lines.

The biological activity of both cyclophosphazenes and peptides makes these compounds important for new studies in medicinal chemistry. For this purpose, five different phosphazene-peptide conjugates synthesized from dichlorocyclotriphosphazene and tyrosine-containing tripeptides. The synthesized compounds were evaluated for their in vitro cytotoxic activities against human breast (MCF-7) and colon (Caco-2) cancer cell lines using MTT assay. The derivatives induced cell death through DNA damage, with notable effects in Caco-2 cell lines. Specifically, DTVV, DTVG, and DTVA were cytotoxic at 50 and 100 μM, while DTVP and DTVM were effective at 25, 50, and 100 μM. DTVM outperformed Tamoxifen at 50 μM in the MCF-7 cell line. DNA damage studies of the compounds were performed using the comet assay method, evaluating tail length, tail density, olive tail moment, head length, and head density parameters. The findings indicated that cell death occurred via a DNA damage mechanism. The molecular intricacies of DTVA, DTVG, DTVM, DTVP and DTVV within the VEGFR2 kinase domain (3VHE) and Cyclophilin_CeCYP16-Like Domain (2HQ6) binding pockets and various interactions, docking scores and potential activities of these derivatives were investigated. The differences in docking scores and interaction profiles highlight the potential efficacy and specificity of these compounds in targeting breast and colon cancer cells. These findings highlight the potential of phosphazene-peptide derivatives as therapeutic agents in cancer treatment.

Development, characterization, and assessment of PLAROsomal vesicular system of curcumin for enhanced stability and therapeutic efficacy

BackgroundCurcumin (CUR) is a natural polyphenol and one of the key phytoconstituents found in the rhizomes of Curcuma Longa. It exhibits various pharmacological properties, encompassing antioxidant, anticancer effects, antiseptic, and anti-inflammatory, among several others.A significant drawback of using CUR is its limited bioavailability, which primarily depends on gut microorganisms responsible for converting it into its bioavailable form. Therefore, the contemporary study intended to formulate a novel PLAROsomal vesicular delivery of CUR, i.e., CUR-PLAROsomes employing a design of experiments approach to examine the influence of various process parameters, such as particle size and drug percentage release.ResultThe prepared CUR-PLAROsomes were characterized for their physicochemical properties using various hyphenated tools. The CUR-PLAROsomes exhibited sizes ranging from 40 to 300 nm, and the optimized batch demonstrated a drug entrapment of 86.38 ± 0.22%.In-vitro anticancer studies were conducted using human colorectal adenocarcinoma cells (COLO320DM) and human breast adenocarcinoma (MCF-7). CUR-PLAROsomes exhibited significant in-vivo anti-inflammatory potential against carrageenan-induced paw edema. CUR-PLAROsomes were more potent against COLO320DM and MCF-7 cell lines, even at lower concentrations, than pure CUR.ConclusionFurthermore, based on the observations, it exhibits potential as an anti-inflammatory agent, suggesting that PLAROsomes are an effective vesicular drug delivery system.HighlightsNewly introduced PLARosome is a next generation of Liposomes which have gain popularity owing to its better adaptability to overcome leakage problem of vesicular drug delivery system.This is the pioneer attempt to prepare Curcumin-loaded PLARosome as an anti-cancer and anti-inflammatory activity.Nano size of the PLAROsomes may contribute to enhance the efficacy of Curcumin as a target specific drug delivery system.Site specific delivery of phytoconstituents is possible by use of PLAROsomes as a novel drug delivery system.Graphical abstract

Preliminary phase results of GC-MS analysis and cytotoxic activity of Argemone mexicana leaves methanol extract against MCF-7 cell lines

Argemone mexicana leaves (AML) contain a variety of bioactive components such as fatty acids, amino acids, phenolics and alkaloids, including Berberine, Isoquinoline, Scoulerine, Stylopine, Thalifone, Benzylisoquinolines, Protopine, and Tetrahydroberberine. This study aimed to examine the gas chromatography and mass spectrometry (GC-MS) analysis of AML extract and its cytotoxic activity on MCF-7 cell lines to identify an alternative source for anticancer treatment. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was utilized to assess the viability of AML extract-treated cells, while the apoptotic assay involved Acridine orange staining to determine the mode of cell death based on morphological and nuclear fragmentation. The GC-MS analysis was used to identify the biologically active compounds. The results showed that the percentage of cell viability after AML extract treatment ranged from 28.50% to 64.28% for concentrations of 1000 to 125 μg/ml (IC50 = 258.87 μg/ml). Statistical analysis revealed a significant difference in cell viability (p < 0.05). Exposure of cells to AML extract stimulated apoptosis through membrane blebbing, cell shrinkage, cytoplasm condensation, and nuclear fragmentation. Forty-one compounds were identified by GC-MS in the AML extract. Based on the peak area, some major compounds included n-Hexadecanoic acid (palmitic acid), 9,12-Octadecadienoic acid (Z, Z)-, Phytol, 9,12,15-Octadecatrienoic acid (Z, Z, Z)-, and 1-methyl piperidine. In conclusion, the bioactive compounds are apparently responsible for the cytotoxic effects of the AML extract, and the in-vitro results highlight the extract’s potential as a source of natural anticancer drugs. However, further investigation is necessary to confirm this.

Design and Synthesis of Various Aryl Amide Derivatives of Imidazo[1,5-a] Pyridine-1,2,4-Thiadiazoles: In Vitro Cytotoxicity Evaluation and In Silico Molecular Docking Studies.

A new series of various aryl amide derivatives of imidazo[1,5-a]pyridine-1,2,4-thiadiazoles (15a-j) were designed, synthesized, and evaluated for their cytotoxic profiles against four human cancer cell lines such as breast cancer (MCF-7), lung cancer (A549), colon cancer (Colo-205), and ovarian cancer (A2780), via the MTT assay, with etoposide as the standard known chemotherapeutic agent. Five compounds, 15a, 15b, 15c, 15f, and 15j, exhibited more potent cytotoxic effects than did etoposide. Among them, compound 15a exhibited potent cytotoxic effects against the MCF-7, A549, Colo-205, and A2780 cell lines, with IC50 values of 0.11±0.045µM, 0.94±0.047µM, 0.39±0.023µM, and 0.77±0.062µM, respectively. Through docking simulations of human topoisomerase IIβ, it is apparent that compounds 15a, 15b, 15c, and 15f manifested exceptional binding affinities and interaction profiles, surpassing the other compounds evaluated in this in silico study.

Down-regulation of ESRP2 inhibits breast cancer cell proliferation via inhibiting cyclinD1

Epithelial splicing regulatory protein 2 (ESRP2),an important alternative splicing protein of mRNA, is reported to have a dual role in tumors, which can promote or inhibit the occurrence and development of tumors. However, the function and mechanism of ESRP2 in breast cancer (BC) remain unclear. The distribution of ESRP2 expression in breast cancer and the correlation between ESRP2 expression and the overall survival rate were detected by The Cancer Genome Atlas (TCGA) database. Gene Ontology(GO)analysis, containing biological process, cellular components, and molecular function, was utilized to evaluate the potential mechanism of ESRP2 in breast cancer. The ESRP2 expression in breast cancer cell lines was detected by real-time quantitative PCR analysis (RT-qPCR) and western blotting. Cell clone was performed to examine the proliferation of ESRP2 knockdown in MCF-7 cells. The cell cycle was measured by flow cytometry assays. The role of ESRP2 knockdown in synergistic effect with chemotherapeutic agents was also determined by MTT assay. Bioinformatics analysis demonstrated that the ESRP2 gene was elevated in breast cancer cells and its overexpression was strongly correlated with shorter overall survival. GO analysis revealed that ESRP2 expression was related to cell proliferation. ESRP2 mRNA and protein expression were elevated in breast cancer cell lines, compared to the normal human breast cell line MCF-10 A. Dwon-regulation of ESRP2 inhibited cell proliferation and promoted the sensitivity of chemotherapy drug, Cisplatin(DDP) and Paclitaxel (TAXOL), in MCF-7 cells.Additionally, ESRP2 knockdown obstructed the cell cycle at the G1 phase and caused a decrease in cyclinD1 protein expression. These findings reveal that ESRP2 is highly expressed in breast cancer and is correlated with poor prognosis in breast cancer patients. ESRP2 knockdown can inhibit MCF-7 cell proliferation by arresting the cell cycle at the G1 phase and promoting the sensitivity of chemotherapy drugs (DDP and TAXOL)in MCF-7 cells. ESRP2 may be required for the regulation of breast cancer progression, as well as a critical target for the clinical treatment of breast cancer.