Michigan Cancer Foundation-7 Cells Research Articles

Exploration of cytotoxicity of iodoquinazoline derivatives as inhibitors of both VEGFR-2 and EGFRT790M: Molecular docking, ADMET, design, and syntheses.

Novel inhibitors of epidermal growth factor receptor (EGFR)T790M/vascular endothelial growth factor receptor-2 (VEGFR-2) were synthesized based on the iodoquinazoline scaffold linked to different heteroaromatic, aromatic, and/or aliphatic moieties. The novel derivatives were in vitro examined for anticancer activities against A549, HCT116, michigan cancer foundation-7 (MCF-7), and HepG2 cells. Molecular modeling was applied to discover their orientation of binding with both VEGFR-2 and EGFR active sites. Compounds 8d, 8c, 6d, and 6c indicated the highest cytotoxicity with IC50 = 6.00, 6.90, 6.12 and 6.24 µM, 7.05, 7.35, 6.80, and 6.80 µM, 5.75, 7.50, 6.90, and 6.95 µM, and 6.55, 7.88, 7.44, and 7.10 µM against the A549, HepG2, HCT116, and MCF-7 cell lines, correspondingly. The cytotoxicity against normal VERO (normal african green monkey kidney cells) of the extremely active eight compounds 6a-d and 8a-d was evaluated. Our compounds exhibited low toxicity concerning normal VERO cells with IC50 = 45.66-51.83 μM. Furthermore, inhibition assays for both the EGFRT790M and VEGFR-2 enzymes were done for all compounds. Remarkable inhibition of EGFRT790M activity was achieved with compounds 6d, 8d, 6c, and 8c at IC50 = 0.35, 0.42, 0.48, and 0.50 µM correspondingly. Moreover, remarkable inhibition of VEGFR-2 activity was achieved with compounds 8d, 8c, 6d, and 6c at IC50 = 0.92, 0.95, 1.00, and 1.20 µM correspondingly. As planned, derivatives 6d, 8d, 6c, and 8c presented exceptional inhibition of both EGFRT790M/VEGFR-2 activities. Finally, in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) studies were made for the highly active four compounds 6c, 6d, 8c, and 8d in comparison with erlotinib and sorafenib as reference standards.

The effectiveness of semi-wild Sumatran mango (Mangifera spp.) leaves as a phytotherapy agent for breast cancer

Background Breast cancer ranks first in the world, standing at a mortality rate of 24.5% per year and is the leading cause of cancer death in Indonesia. The current management of breast cancer therapy is considered less effective because of its careful use due to side effects that are detrimental to the patient. The semi-wild species from Sumatra are neglected and underutilized species but have the potential as a therapeutic agent. Previous research has revealed that this species of mango is high in antioxidant compounds. Objective This study was carried out to discover the anticancer activities of the semi-wild mango species via inhibitory activities and morphological changes in Michigan Cancer Foundation-7 (MCF-7) cells. Materials and methods The IC50 value of Mangifera sumatrana, Mangifera foetida, and Mangifera laurina leaves in n-hexane, ethyl-acetate, and methanol extracts was determined using the reagent 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Data were analyzed by two-way analysis of variance using IBM SPSS Statistics 21. Results and conclusion M. laurina n-hexane extracts exhibited anticancer activity (IC50 13.25 ppm). Nonpolar solutions were chosen as the most effective extraction solvent in anticancer tests because lipids in nonpolar solvents can hit the lipid bilayer. A hexane fraction was created by separating the majority of nonpolar fatty acid esters, and this fraction had a considerable impact on cytotoxic and apoptotic effects on MCF-7 cells. Therefore, all treatments can transform MCF-7 cells’ morphology into blackened dead cells that are degraded into small parts, such as apoptotic bodies in cells undergoing apoptotic processes. MTT assays against MCF-7 on three species of semi-wild Sumatran mango in different extraction solvents showed that n-hexane extracts of M. laurina had stronger anticancer activity than other samples. This study provides new information to support the development of standardized herbal medicines and phytopharmaca in the future.

Comparison of Anticancer Activity Between Thymoquinone and Tamoxifen , Thymoquinone + Tamoxifen 0n Mcf -7 Cell Line of Human Breast Cancer –An Invitro Study.

This study aims at evaluating the anticancer effect on the MCF-7 (Michigan Cancer Foundation-7) cell line of human breast cancer using Thymoquinone and Tamoxifen alone as well as in combination therapy by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) Test. NCCS in Pune provided the MCF-7 cell line. The cells were kept at 37°C in a humidified medium of 50µg/ml CO2 in Minimal Essential Medium added with 10percent FBS (Foetal Bovine Serum), streptomycin (100µg/ml), as well as penicillin (100U/ml). MTT-(3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl tetrazolium bromide) test was conducted on MCF-7 cell line for Thymoquinone and Tamoxifen as sole and combination therapy. Measurements were performed using UV (Ultra-Violet)-spectrophotometer at 570-nanometre absorbance and the content needed for a 50 percent inhibitory concentration (IC50) was calculated and evaluated graphically. IC 50 of Thymoquinone on MCF 7 was found to be at 31.2 µg/ml and Tamoxifen was at 62.5 µg/ml were as in combination therapy the IC 50 was found to be at 7.8 µg/ml. There is a remarkable reduction in concentration to achieve IC 50 percentage in combination therapy with a comparison with individual therapy. Therefore, the combination therapy of Thymoquinone and Tamoxifen on the MCF-7 cell line is more efficacious when compared to individual treatment on cell viability inhibition.

Cholesteryl ester transfer protein knock-down in conjunction with a cholesterol-depleting agent decreases tamoxifen resistance in breast cancer cells.

The cholesterogenic phenotype, encompassing de novo biosynthesis and accumulation of cholesterol, aids cancer cell proliferation and survival. Previously, the role of cholesteryl ester (CE) transfer protein (CETP) has been implicated in breast cancer aggressiveness, but the molecular basis of this observation is not clearly understood, which this study aims to elucidate. CETP knock-down resulted in a >50% decrease in cell proliferation in both 'estrogen receptor-positive' (ER+; Michigan Cancer Foundation-7 (MCF7) breast cancer cells) and 'triple-negative' breast cancer (TNBC; MDA-MB-231) cell lines. Intriguingly, the abrogation of CETP together with the combination treatment of tamoxifen (5 μM) and acetyl plumbagin (a cholesterol-depleting agent) (5 μM) resulted in twofold to threefold increase in apoptosis in both cell lines. CETP knockdown also showed decreased intracellular CE levels, lipid raft and lipid droplets in both cell lines. In addition, RT2 Profiler PCR array (Qiagen, Germany)-based gene expression analysis revealed an overall downregulation of genes associated in cholesterol biosynthesis, lipid signalling and drug resistance in MCF7 cells post-CETP knock-down. On the contrary, resistance in MDA-MB-231 cells was reduced through increased expression in cholesterol efflux genes and the expression of targetable surface receptors by endocrine therapy. The pilot xenograft mice study substantiated CETP's role as a cancer survival gene as knock-down of CETP stunted the growth of TNBC tumour by 86%. The principal findings of this study potentiate CETP as a driver in breast cancer growth and aggressiveness and thus targeting CETP could limit drug resistance via the reduction in cholesterol accumulation in breast cancer cells, thereby reducing cancer aggressiveness.

A 3D printing assisted microfluidic absorbance-based measurement system for biological assay

Development of rapid analytical systems utilizing 3D printing is an emerging area of interest with the potential to provide efficient solutions by integrating multidisciplinary technology without compromising the quality of the system. In this study we report the fabrication of a 3D printing assisted microfluidic based absorbance measurement system, leveraging 3D printing along with integrating miniature optical components for the accurate measurement of biological assays. The developed system is rapid, affordable, and compact, through set of computer-aided design models and fusion deposition modeling 3D printing along with relevant electronic circuitry involving optical components like surface mounting devices. The handheld device features a capacitive touchscreen display, programmed to seamlessly perform MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The device was employed for assessing the cell viability using Michigan cancer foundation-7 (MCF-7) cell lines over varying concentrations of tamoxifen, reciprocating the MTT assay analysis conducted by using spectrophotometer. The device achieved excellent results which upon comparison with the conventional spectrophotometer-based results have shown a correlation coefficient of 0.98. This compact and rapid absorbance measurement system holds significant potential for evaluating the cytotoxicity of drugs, and further development of innovative analytical devices.

Dissecting Combinational Mechanisms of Herbal Formula from a Transcriptome-based Multi-scale Network Pharmacology Model

Abstract Objective: Illumination of the integrative effects of herbs in a formula is a bottleneck that limits the development of traditional Chinese medicine (TCM). In the present study, we developed a transcriptome-based multi-scale network pharmacology model to explore the combined effects of different herbs. Materials and Methods: First, we curated gene signatures at different biological scales, from the molecular to higher tissue levels, including tissues, cells, pathological processes, biological processes, pathways, and targets. Second, using the Xiexin Tang (XXT) formula as an example, we collected transcriptomic data in response to the treatment of XXT or its three compositive herbs on Michigan cancer foundation7 cells. Third, we linked each herbal drug to different biological scales by calculating the correlation scores between herb-induced gene expression profiles and gene signatures. Finally, the combined mechanisms of the three constituent herbs in XXT were deciphered by comparing their multi-scale effects with those of the formula. Results: The results showed that although XXT or single herbs regulated a large number of signatures on each biological scale, the phenotypic effects of these herbal drugs are concentrated onto the “Blood” tissue, types of hemocytes, and hemorrhagic injury-related pathological processes. At the molecular level, these herbs consistently regulate processes such as the cell cycle and blood coagulation-related pathways, as well as protein targets related to the immunoinflammatory response and blood coagulation, such as proteinase-activated receptor 2, integrin beta-3, inhibitor of nuclear factor kappa-B kinase subunit beta, and coagulation factor XII. The analysis of the combinational modes demonstrated that different herbs can cooperate by acting on the same objects and/or regulating different objects in related functions, and cooperative behaviors change at different biological scales. Conclusions: Our model can dissect the combined effects of herbal formulae from a multi-scale perspective and should be beneficial for the development and exploitation of TCM.

Evaluation of the Recombinant Bacterial Chitinases as Anti-proliferative and Anti-migratory Agents for the Human Breast Cancer Cell Line, MCF-7.

Chitinases, a glycosyl hydrolase family 18 members, have a wide distribution in both prokaryotes and eukaryotes, including humans. Regardless of the absence of endogenous chitin polymer, various chitinases and chitinase-like proteins (CLPs) have been reported in mammals. However, several other carbohydrate polymers, such as hyaluronic acid and heparan sulfate, show structural similarities with chitin, which could be a potential target of chitinase and CLPs. Heparan sulfate is part of the integral membrane proteins and involves in cell adherence and migration. Hence, to demonstrate the effect of chitinase on cancer cell progression, we selected two chitinases from Serratia marcescens, ChiB and ChiC, which function as exo- and endo-chitinase, respectively. The ChiB and ChiC proteins were produced recombinantly by cloning chiB and chiC genes from Serratia marcescens. The cell viability of the Michigan Cancer Foundation-7 (MCF-7) cells was studied using different concentrations of the purified recombinant proteins. Cell viability assay was performed using 3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide and water-soluble tetrazolium salt, and the effect of ChiB and ChiC on cell proliferation was studied by clonogenic assay. The cell migration study was analysed by wound healing, transwell migration, and invasion assays. Cell cycle analysis of propidium iodide-stained cells and cell proliferation markers such as pERK1/2, pAKT, and SMP30 were also done. It was observed that both ChiB and ChiC were able to impede cell viability, cell migration, and invasion significantly. These observations and our in silico molecular docking analysis suggest that ChiC is a potential anticancer agent and is more efficient than ChiB. Since the ChiC is able to inhibit both cancer cell proliferation and migration, it could be a potential candidate for the treatment of metastatic cancer.

The obeticholic acid can positively regulate the cancerous behavior of MCF7 breast cancer cell line.

The diagnosis and treatment processes of cancer are among the main challenges of medical science in recent decades. The use of different therapeutic agents is one of the most common methods frequently utilized for cancer treatment. Accumulating evidence points to a potential effect of Obeticholic acid (OCA), a specific ligand for farnesoid X receptor, on the regulation of cancer-associated pathways. In spite of tremendous efforts to introduce OCA into the clinical setting, there is a great deal of uncertainty about its impact on breast cancer treatment. This study was performed to evaluate the effects of OCA on breast cancer. In this experiment, the MCF-7 (Michigan Cancer Foundation-7) cell line was treated with 0.1 µM OCA, and cancerous characteristics of the MCF-7 cell line was evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay, gelatin zymography, western blot, Real-time PCR, flow cytometry, and ELISA techniques. The results indicated that OCA increased the rate of apoptosis and the expression levels of PPARα (Peroxisome proliferator-activated receptor alpha) and TIMP-1 (tissue inhibitor of metalloproteinase-1) genes in this cell line, while it reduced the mRNA levels of MMP7 (matrix metalloproteinase 7) and Bcl-2 (B-cell lymphoma 2) genes, as well as the protein levels of the active form of AKT (protein kinase B), Erk1/2 (extracellular signal-regulated kinase 1/2) and STAT3 (Signal transducers and activators of transcription-3). Also, OCA decreased the activity of MMP9, while it increased the secretion of VEGF-A (vascular endothelial growth factor-A). It seems that OCA can exert anti-cancer effects on the MCF-7 cells by reducing growth, proliferation, migration, invasion, and regulation of the expression of genes involved in cancer-associated pathways. However, it should be noted that further studies are warranted to establish this concept, especiallythe increase of VEGF-Acan be considered a challenge for the results of this study.

NANOPARTICLE PREPARATION OF SIAM CITRUS PEEL EXTRACT (CITRUS NOBILIS L. VAR. MICROCARPA) USING SHORT-CHAIN CHITOSAN AND TRIPOLYPHOSPHATE AS CROSS LINKER AND CELLULAR UPTAKE STUDY ON MCF-7 CELL LINE BY IN VITRO

Objective: High consumption of oranges causes a lot of orange peel waste. Orange peel contains the compound naringenin, which has a cytotoxic effect on various cancer cells. This research aims to develop a preparation of Siamese orange peel extract nanoparticles with short-chain chitosan and tripolyphosphate carriers as an oral drug delivery system and determine its cytotoxic activity against the Michigan Cancer Foundation-7 (MCF-7) cell line. Methods: This research uses the micro tetrazolium (MTT) method to see the cytotoxic activity extract of methanol obtained from maceration extraction. The extract was then formulated into nanoparticles using chitosan and tripolyphosphate. Characterization and evaluation of nanoparticles were carried out, including particle size, zeta potential, entrapment efficiency, and stability in the stomach using 0.1 N HCl and in the intestine using Artificial Intestinal Fluid (AIF) in vitro. This research was also conducted to assess the ability of nanoparticles to enter MCF-7 cells (cellular uptake). Results: Nanoparticles were successfully developed from Siamese orange peel extract. The results of the day 0 nanoparticle characterization were spherical, with average particle size 284.3 nm, zeta potential 0.713 mV, entrapment efficiency 96.73%, and stability in 0.1 N HCl at the 0th hours, respectively. 1st, 2nd, and 3rd. 99.16%, 98.70%, 98.47%, 98.31%, stability on AIF at hours 0, 1, 2, 3 and 4 respectively 99.52%, 99.30%, 99.40%, 98.99%, 99.29%. Characterization of nanoparticles on day 25 showed that the average particle size was 196.2 nm, zeta potential 0.476 mV, entrapment efficiency 96.92%, stability in 0.1 N HCl at 0, 1, 2 and 3 h respectively 99.51%, 98.67%, 98.51%, 98.27%, stability in AIF at 0th, 1st, 2nd, 3rd, and 4th hours 99.24 respectively %, 98.76%, 98.46%, 97.93%, 97.58%. Cytotoxic activity of extract Siamese citrus peel against MCF-7 cells with IC50 of 290.58 µg/ml. The result shows that cellular uptake of Siamese citrus peel nanoparticles can penetrate MCF-7 cells. Conclusion: Stable nanoparticles were successfully developed from Siamese orange peel extract, and their stability was maintained throughout a 30-day storage period. This extract displayed cytotoxic effects and showcased the ability for cellular uptake in MCF-7 cell cultures in vitro.

Anti-cancer potential of sea grape (Caulerpa racemosa) extract by altering epithelial-mesenchymal transition and pro-apoptosis proteins expression in MCF-7 breast cancer cells

Breast cancer is a neoplasm that is increasing globally based on its prevalence. Caulerpa racemosa is a type of sea grape that has anti-cancer activity based on previous studies. We aim to determine the anti-cancer activity of C. racemosa extract on Michigan cancer foundation-7 (MCF-7) breast cancer cells through the mechanism of apoptosis by observing cell viability and caspase-3 expression, also as an anti-metastatic agent on expression of Snail and Vimentin. A true experimental study was carried out using a randomized post-test-only control group design. MCF-7 cells were used as subjects with the intervention of C. racemosa extract at varying doses. Cell apoptotic was assessed by flow cytometry and cell viability test, while anti-metastatic activity was assessed by wound healing assay. Immunofluorescence staining was used to assess the expression level of caspase-3, Snail, and Vimentin. The results showed an increased activity of cell apoptosis, according to flow cytometry and cell viability tests. Furthermore, expression of caspase-3 was found to be significantly higher in the 400 g/ml dose group and MCF-7 cell migration inhibition by decreasing Snail and Vimentin protein expression. These results indicate a “novel mechanism” of C. racemosa in the MCF-7 model as an anti-cancer and anti-metastatic agent to inhibit breast cancer progression.

In vitro anti-cancer potency of Mortierella elongata lipids against MCF 7 cells through induction of apoptosis and cell cycle arrest

Globally, cancer remains the second-whacking cause of mortality. Several studies, like in vitro cell studies, clinical trials, in vivo studies, and cohort studies, have authenticated the anticancer potency of omega-3 polyunsaturated fatty acids (PUFA) against various cancer types. The present study reports the in vitro anticancer potency of PUFA produced by Mortierella elongata (Accession No. OK402027) against Michigan Cancer Foundation-7 (MCF-7) breast cancer cell lines. The biocompatibility and cytotoxicity of M. elongata lipids were evaluated against human embryonic kidney and MCF-7 cells, respectively. The anti-proliferative activity of M. elongata lipids was examined at three different concentrations based on the inhibitory concentration (IC50) value. The apoptotic activity of M. elongata lipids was analyzed by fluorescence microscopy by implementing three different staining methods, such as acridine orange/ethidium bromide, 4,6-diamidino-2-phenylindole, and propidium iodide. Further, the biological activity of M. elongata on apoptosis induction, cell cycle progression, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) generation were evaluated. The MTT assay revealed the anti-proliferative activity of M. elongata lipids, and the IC50 value of M. elongata lipids at 24 h was found to be 28 ± 1.3 μg/mL. A significant decrease in the percentage of live cells with 57.36% of apoptotic and 14.10% of necrotic cells was revealed in cells treated with 100 μg/mL of M. elongata lipids. Anti-proliferative activity is associated with increased ROS generation and the loss of MMP. The lipids of M. elongata induced a dose-dependent G1 arrest and were found to be more effective at 100 μg/ml, accumulating 54.49% of MCF-7 cells in the G1 phase. Taken together, the present study has confirmed the in vitro anticancer potency of M. elongata lipids via apoptosis and cell cycle arrest.

Catalytic, Antifungal, and Antiproliferative Activity Studies of a New Family of Mononuclear [VIVO]/[VVO2] Complexes.

Ligands derived from 2-(1-phenylhydrazinyl)pyridine and salicylaldehyde (HL1), 3-methoxysalicylaldehyde (HL2), 5-bromosalicylaldehyde (HL3), and 3,5-di-tert-butylsalicylaldehyde (HL4) react with [VIVO(acac)2] in MeOH followed by aerial oxidation to give [VVO2(L1)] (1), [VVO2(L2)] (2), [VVO2(L3)] (3), and [VVO2(L4)] (4). Complex [VIVO(acac)(L1)] (5) is also isolable from [VIVO(acac)2] and HL1 in dry MeOH. Structures of all complexes were confirmed by single-crystal X-ray and spectroscopic studies. They efficiently catalyze benzyl alcohol and its derivatives' oxidation in the presence of H2O2 to their corresponding aldehydes. Under optimized reaction conditions using 1 as a catalyst precursor, conversion of benzyl alcohol follows the order: 4 (93%) > 2 (90%) > 1 (86%) > 3 (84%) ≈ 5 (84%). These complexes were also evaluated for antifungal and antiproliferative activities. Complex 3 with MIC50 = 16 μg/mL, 4 with MIC50 = 12 μg/mL, and 5 with MIC50 = 16 μg/mL are efficient toward planktonic cells of Candida albicans and Candida tropicalis. On Michigan cancer foundation-7 (MCF-7) cells, they show comparable cytotoxic effects and exhibit IC50 in the 27.3-33.5 μg/mL range, and among these, 4 exhibits the highest cytotoxicity. A similar study on human embryonic kidney cells (HEK293) confirms their less toxicity at lower concentrations (4 to 16 μg/mL) compared to MCF-7.

Synthesis of novel pyrimido[4,5-b]quinoline derivatives as dual EGFR/HER2 inhibitors as anticancer agents.

A series of novel N-aryl-5-aryl-6,7,8,9-tetrahydropyrimido[4,5-b]quinolin-4-amines 4a-4l was synthesized as potential anticancer agents through Dimroth rearrangement reaction of intermediates 3a-3c. Pyrimido[4,5-b]quinolines 4a-4l showed promising activity against the Michigan Cancer Foundation-7 (MCF-7) cell line, compared with lapatinib as the reference drug. Compounds 4d, 4h, 4i, and 4l demonstrated higher cytotoxic activity than lapatinib, with IC50 values of 2.67, 6.82, 4.31, and 1.62 µM, respectively. Compounds 4d, 4i, and 4l showed promising epidermal growth factor receptor (EGFR) inhibition with IC50 values of 0.065, 0.116, and 0.052 µM, respectively. These compounds were subjected to human epidermal growth factor receptor 2 (HER2) inhibition and showed IC50 values of 0.09, 0.164, and 0.055 µM, respectively. Compounds 4d, 4i, and 4l are good candidates as dual EGFR/HER2 inhibitors. The most active compound, 4l, was subjected to cell-cycle analysis and induced cell-cycle arrest at the S phase. Compound 4l induced apoptosis 60-fold compared with control untreated MCF-7 cells. 4l can inhibit cancer metastasis. It reduced MCF-7 cell infiltration and metastasis by 45% compared with control untreated cells.

Designing and fabrication of colloidal nano-phytosomes with gamma-oryzanol and phosphatidylcholine for encapsulation and delivery of polyphenol-rich extract from pomegranate peel

Nano-carriers are well-known delivery systems to encapsulate different bioactive compounds and extracts. Such nano-systems are used in various food and drug areas to protect active ingredients, increase bioavailability, control the release, and deliver bioactive substances. This study aimed to design and fabricate a stable colloidal nano-delivery system to better preserve the antioxidant properties of pomegranate peel extract (PPE) and protect its sustained release in a gastrointestinal model. To achieve this goal, a nano-phytosomal system was fabricated with plant-based, cost-effective, and food-grade compounds, i.e., phosphatidylcholine (PC) and gamma-oryzanol (GO) for encapsulation of PPE. To fabricate the nano-phytosomes, thin film hydration/sonication method was used. The parameters of particle size, zeta potential, polydispersity index (PDI), loading capacity (LC), and encapsulation efficiency (EE) were investigated to evaluate the efficiency of the produced nano-system. In summary, the size, zeta potential, PDI, LC, and EE of homogenous spherical PC-GO-PPE nano-phytosomes (NPs) in the ratio of 8:2:2 % w/w were achieved as 60.61 ± 0.81 nm, −32.24 ± 0.84 mV, 0.19 ± 0.01, 19.13 ± 0.30 %, and 95.66 ± 1.52 %, respectively. Also, the structure of NPs was approved by Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscope (SEM). The optimized NPs were stable during one month of storage at 4 °C, and changes in the size of particles and PPE retention rate were insignificant (p > 0.05). The nano-encapsulation of PPE significantly decreased the loss of its antioxidant activity during one month of storage at 4 °C. The optimized NPs exhibited prolonged and sustained release of PPE in a gastrointestinal model, so that after 2 h in simulated gastric fluid (SGF) and 4 h in simulated intestinal fluid (SIF), 22.66 ± 2.51 % and 69.33 ± 4.50 % of initially loaded PPE was released, respectively. Optimized NPs had considerable cytotoxicity against the Michigan Cancer Foundation-7 cell line (MCF7) (IC50 = 103 μg/ml), but not against Human Foreskin Fibroblast cell line (HFF-2) (IC50 = 453 μg/ml). In conclusion, spherical PC-GO-PPE NPs were identified as a promising delivery system to efficiently encapsulate PPE, as well as protect and preserve its bioactivity, including antioxidant and cytotoxicity against cancer cell line.

The Role of Mitochondrial Dysfunction in Cytotoxic Effects of Solanum nigrum Water Extract on MCF-7 and MDA-MB-231 Breast Cancer Cells.

Recent studies suggest that numerous naturally occurring agents have the potential to kill cancer cells via mitochondrial dysfunction. Solanum nigrum is a herb widely used in alternative medical systems. This study aimed to investigate the cytotoxic effect of Solanum nigrum water extract (SNWE) against Michigan Cancer Foundation-7 (MCF-7) and MD Anderson-Metastatic Breast Cancer-231 (MDA-MB-231) cells. We used an MTT reduction assay for cytotoxicity analysis. To explore the mode of action, the cellular adenosine triphosphate (ATP) levels and mitochondrial membrane potential were analyzed using a colorimetric ATP assay and Rhodamine-123 fluorescent staining, respectively, during SNWE treatment for 72 h. The cytotoxic effect was significant in both cell lines, with IC50 values of 4.26 µg/mL and 5.30 µg/mL in MCF-7 and MDA-MB-231 cells, respectively. The 24, 48, and 72 h treatments of 100 µg/mL SNWE showed 0.85 ± 0.07, 0.38 ± 0.1, and 0.20 ± 0.1 nM ATP in MCF-7 cells and 0.94 ± 0.07, 0.84 ± 0.2 and 0.46 ± 0.2 nM in MDA-MB-231 cells, respectively. The SNWE treatment altered the mitochondrial membrane potential (ΔΨm) in a concentration-dependent manner in both the breast cancer cell lines, to 29.6 ± 4.1% in MCF-7 and 28.7 ± 4.17% in MDA-MB-231 cells, when compared with healthy mitochondria (100% ΔΨm). The cytotoxic effects of Solanum nigrum against breast cancer cells are associated with energy metabolism. Additional studies are warranted to test the anticancer effect of Solanum nigrum using an animal model of breast cancer.

Coordination behavior of cocaine toward d-block metal ions: Synthesis, spectral analysis, density functional theory (DFT) studies, and chemotherapeutic activity

The exploration of novel bioactive metallopharmaceuticals for the treatment of diseases such as microbial infections or cancer, with a focus on reducing side effects and drug resistance, is a prominent area of investigation within the field of medicinal inorganic chemistry. In this study, a new series of binary cocaine (COC) metal complexes with some d-block metal ions were synthesized and structurally characterized. Except for Co(II) and Ni(II) complexes, which had a 1:2 metal-to-ligand stoichiometric ratio, all of the produced complexes were found to have a 1:1 metal-to-ligand stoichiometry. The Fe(III) and Cd(II) complexes were further analysed through theoretical density functional theory (DFT) calculations to investigate their geometry optimization and electronic transitions. The anticancer activity of the complexes was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The Co(II) complex demonstrated potential cytotoxic effects against the hepatoblastoma (HepG-2) and Michigan Cancer Foundation-7 (MCF-7) cell lines, with IC50 values of 9.78 µM and 10.36 µM, respectively. Moreover, it exhibited good safety on human normal cells. Additional research was conducted on the Co(II) complex to explore its impact on cellular concentrations of the human p21 and p27 tumor suppressor nuclear proteins, as well as its effects on apoptosis, metastasis, and oxidative stress in the MCF-7 cancer cell line. The findings revealed that the Co(II) complex showed promising antiproliferative and antimetastatic properties while maintaining a high level of safety and tolerability on normal cells. The antimicrobial activity of the complexes was also investigated, with both the Cr(III) and Ni(II) complexes exhibiting antibacterial activity comparable to the standard gentamicin against Escherichia coli. Additionally, the Fe(III) and Cd(II) complexes demonstrated inhibitory effects on Salmonella typhimurium equivalent to that of gentamicin.

Highly efficient and simultaneous production of thirteen taxanes from Taxus × media and mining of their new bioactivity

Taxus serves as a primary natural source of paclitaxel, a valuable anticancer drug. Developing an efficient and synchronous separation and purification process for the abundant taxanes in Taxus, as well as mining their potential bioactive, can not only improve the production efficiency of paclitaxel but also further reduce the production cost. In this study, the abundant taxanes in the leaves and branches of Taxus × media, as well as the intermediates obtained during the purification process, were analyzed by high-performance liquid chromatography (HPLC) in combination with high-resolution accurate-mass spectrometry (LC-HR-MS/MS). Subsequently, thirteen taxanes were successfully separated and purified to a purity of over 98% with a recovery rate of 61% in a pilot-scale production. Notably, the purity and recovery of paclitaxel were increased to over 99.2% and 78.2%, respectively. Interestingly, taxuspine M was identified for the first time to exhibit superior binding properties with poly ADP-ribose polymerase 1 (PARP1) and NRH:quinone oxidoreductase 2 (NQO2) proteins, which were highly associated with breast cancer, through virtual screening across the human disease therapeutic protein in the therapeutic target database (TTD). Moreover, taxuspine M demonstrated significant anti-proliferative ability against the Michigan Cancer Foundation-7 (MCF-7) cell line with an IC50 value of 195.5 nM, indicating its potential as an anticancer agent. This study provides an improved scalable process for the highly efficient and comprehensive utilization of plant-source pharmaceutical resources.

Synthesis of Zeolitic imidazolate frameworks-8@ layered double hydroxide polyhedral nanocomposite with designed porous voids as an effective carrier for anti-cancer drug-controlled delivery.

In nanotechnology, compounds containing metal materials are used in pharmaceutical sciences. The main purpose of this research was to introduce a novel method to control the amount of zeolite imidazolate framework (ZIF) in water by forming a protective layer such as layered double hydroxide (LDH). Firstly, ZIF was synthesised as the nucleus of the nanocomposite, and then LDH was formed by in situ synthesis as a protective layer. Scanning electron microscope, Fourier-transform infrared spectroscopy, X-Ray Diffraction, and Brunauer, Emmett and Teller techniques were used to determine (ZIF-8@LDH chemical structure and morphology. Our findings revealed that the ZIF-8@LDH-MTX complex could interact with carboxyl groups and trivalent cations by creating a bifurcation bridge, clarity, and high thermal stability. The antibacterial test indicated that ZIF-8@LDH was able to inhibit pathogenic growth. 2,5-Diphenyl-2H-Tetrazolium Bromide assay results showed that ZIF-8@LDH alone had no notable cytotoxic effect on Michigan Cancer Foundation-7 (MCF-7) cancer cells. However, the cytotoxicity rate was significantly increased in treated MCF-7 cells with ZIF-8@LDH-MTX compared to that of treated cells with methotrexate alone, which can be reasoned by the protection of drug structure and increasing its permeability. The drug release profile was constant at pH=7.4. All findings indicated that the ZIF-8@LDH complex could be considered a newly proposed solution for effective anti-cancer drug delivery.

Efficacy of resveratrol against breast cancer and hepatocellular carcinoma cell lines.

To evaluate the anti-cancer effect of resveratrol on Michigan cancer foundation-7 (MCF-7) and hepatoblastoma cell line (HepG2) cells. The study was carried out at the Department of Botany and Microbiology, Prince Sattam bin Abdulaziz University, Al-kharj, Saudi Arabia, from August 2022 to October 2022. Different concentrations of resveratrol were added to the MCF-7 and HepG2 cell lines. Cell death and proliferation were measured with MTT and Trypan blue exclusion assays. Apoptosis markers were assessed by using a quantitative PCR assay (qPCR). The resveratrol was shown to suppress the proliferation of MCF-7 and HepG2 cells at dose- and time-dependent. The cytotoxic effect of resveratrol was observed even at 100 μM after 24 hours. In comparison to untreated cells, resveratrol treatment reduced the viability of MCF-7 cells to roughly 57.5% with a half maximal inhibitory concentration (IC50) of 51.18 μM and HepG2 cells to 56.2% with an IC50 of 57.4 μM. Furthermore, in the tested cell lines, resveratrol was able to induce apoptosis mediated by elevated apoptosis markers. Resveratrol appears to be an excellent candidate agent in anticancer therapy in various human cancers.

Repeated exposure to 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) accelerates ligand-independent activation of estrogen receptors in long-term estradiol-deprived MCF-7 cells

It was previously identified that there may be an active metabolite of bisphenol A (BPA), 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP). An in vitro system was developed to detect MBP toxicity to the Michigan Cancer Foundation-7 (MCF-7) cells that had been repeatedly exposed to a low dose of the metabolite. MBP profoundly activated estrogen receptor (ER)-dependent transcription as a ligand, with an EC50 of 2.8 nM. Women are continuously exposed to numerous estrogenic environmental chemicals; but their susceptibility to these chemicals may be significantly altered after menopause. Long-term estrogen-deprived (LTED) cells, which display ligand-independent ER activation, are a postmenopausal breast cancer model derived from MCF-7 cells. In this study, we investigated the estrogenic effects of MBP on LTED cells in a repeated exposure in vitro model. The results suggest that i) nanomolar levels of MBP reciprocally disrupt the balanced expression of ERα and ERβ proteins, leading to the dominant expression of ERβ, ii) MBP stimulates ERs-mediated transcription without acting as an ERβ ligand, and iii) MBP utilizes mitogen-activated protein kinase and phosphatidylinositol-3 kinase signaling to evoke its estrogenic action. Moreover, the repeated exposure strategy was effective for detecting low-dose estrogenic-like effects caused by MBP in LTED cells.