Anti-breast Cancer Activity Research Articles

Solvent effects on the structural, spectroscopic, electronic properties, NCI-RDG analysis, molecular docking and molecular dynamics studies of 1-benzyl-indole-3-carbinol

This investigation focuses on the 1-benzyl-indole-3-carbinol (1-benzyl-I3C) molecule and its capacity as a drug to combat breast cancer. The research employs different computational approaches including DFT simulations, molecular docking, and molecular dynamics calculations. The molecular configuration of 1-benzyl-I3C was optimized in the COSMO solvation model, using B3LYP/cc-pVTZ basis set. The modes of vibration of the compound were identified through Potential Energy Distribution (PED) simulations, and the results were found to be consistent with the available FT-IR and Raman data. The analysis of Natural Bond Orbitals (NBO) supports the idea that 1-benzyl-I3C has bioactive properties. The impact of solvents on the electronic characteristics of studied molecule is discussed. The reactive sites of 1-benzyl-I3C were confirmed by the local reactivity descriptors and the molecular electrostatic potential (MEP) surface analyses. Additionally, Non-covalent interaction (NCI) analysis confirms the existence of the Van der Waals interactions in the compound under investigation. Anti-breast cancer activities of the 1-benzyl-I3C molecule were examined based on molecular docking analysis, which reveals a good inhibitor nature of the studied molecule against the progesterone receptor (PR). The molecular dynamics analysis through the RMSD, RMSF, and Rg plots confirms the overall stability of the obtained 1-benzyl-I3C-PR complex.

Retraction Note to: Pyran Derivatives: Anti-Breast Cancer Activity and Docking Study

Retraction Note to: Pyran Derivatives: Anti-Breast Cancer Activity and Docking Study

Integrated Network Ethnopharmacology, Molecular Docking, and ADMET Analysis Strategy for Exploring the Anti-Breast Cancer Activity of Ayurvedic Botanicals Targeting the Progesterone Receptor

Abstract Background: In women, breast cancer is currently among the most common cancers and the second major cause of cancer-related mortality. One therapeutic target for breast cancer is the progesterone receptor (PR), which can be inhibited by specific PR modulators. Methods: Current anti-cancer medications have notorious adverse effects. Consequently, an urgent need exists to identify less hazardous, more effective medicines with few to no adverse effects. One strategy uses ancient herbal remedies to create medications derived from nature. Herein, we used data from the Dr. Duke, IMPPAT, PubChem, Binding DB, UniProt, and DisGeNET databases to construct a network in Cytoscape 3.10.0. Through a polypharmacology approach, bioactives with similarity indices greater than 0.6 were screened and docked with the PR. The top ten ligands with good docking scores were further subjected to interaction analysis in AutoDock v.4.2 software. We additionally analyzed the ADMET properties of the phytochemicals. Results: Procurcumenol and alpha-turmerone exhibited superior interactions with PR, with binding affinities of −7.85 kcal/mol. All compounds met Lipinski’s rule of five and were effective ligands for the PR according to ADMET data analysis. Our findings suggest that procurcumenol and alpha-turmerone may serve as potential anti-breast cancer agents; specifically targeting the PR in breast cancer cells. Conclusion: Understanding of anti-breast cancer activity can be facilitated through experimental validation of network analysis and molecular docking findings.

Synthesis of some novel benzimidazole derivatives act as antibreast cancer activity

Synthesis of some novel benzimidazole derivatives act as antibreast cancer activity

In-silico prediction of anti-breast cancer activity of ginger (Zingiber officinale) using machine learning techniques.

Indonesian civilization extensively uses traditional medicine to cure illnesses and preserve health. The lack of knowledge on the security and efficacy of medicinal plants is still a significant concern. Although the precise chemicals responsible for this impact are unknown, ginger is a common medicinal plant in Southeast Asia that may have anticancer qualities. Using data from Dudedocking, a machine-learning model was created to predict possible breast anticancer chemicals from ginger. The model was used to forecast substances that block KIT and MAPK2 proteins, essential elements in breast cancer. Beta-carotene, 5-Hydroxy-74'-dimethoxyflavone, [12]-Shogaol, Isogingerenone B, curcumin, Trans-[10]-Shogaol, Gingerenone A, Dihydrocurcumin, and demethoxycurcumin were all superior to the reference ligand for MAPK2, according to molecular docking studies. Lycopene, [8]-Shogaol, [6]-Shogaol, and [1]-Paradol exhibited low toxicity and no Lipinski violations, but beta carotene had toxic predictions and Lipinski violations. It was anticipated that all three substances would have anticarcinogenic qualities. Overall, this study shows the value of machine learning in drug development and offers insightful information on possible anticancer chemicals from ginger.

Improved anti-breast cancer activity by doxorubicin-loaded super stealth liposomes.

PEGylation is currently used for the synthesis of stealth liposomes and to enhance the pharmacokinetic and biopharmaceutical properties of payloads. PEGylated dendron phospholipids can decrease the detachment of polyethylene glycol (PEG) from the liposomal surface owing to an increased hydrophobic anchoring effect on the phospholipid bilayer of liposomes and thus generating super stealth liposomes that are suitable for the systemic delivery of anticancer drugs. Herein, doxorubicin hydrochloride-loaded super stealth liposomes were studied for the treatment of breast cancer lung metastasis in an animal model. The results demonstrated that the super stealth liposomes had suitable physicochemical properties for in vivo administration and could significantly increase the efficacy of doxorubicin in breast cancer lung metastasis tumor-bearing mice compared to the free drug. The super stealth liposomes also increased doxorubicin accumulation inside the tumor tissue. The permanence of PEG on the surface of the super stealth liposomes favored the formation of a depot of therapeutic nanocarriers inside the tumor tissue by improving their permanence after stopping treatment. The doxorubicin-loaded super stealth liposomes increased the survival of the mouse tumor model. These promising results demonstrate that the doxorubicin-loaded super stealth liposomes could be an effective nanomedicine to treat metastatic breast cancer.

Ricinodendron heudelotii (Euphorbiaceae) seed oil prevents DMBA-induced breast cancer under menopause-like conditions in Wistar rats.

Despite efforts, breast cancer remains associated with a high incidence and mortality rate. Ricinodendron heudelotii also known as "Njansang," is a plant used for cancer treatment. While several reports on the anticancer potential of its leaves exist, little is known about its seed oil. This study aimed to evaluate the in vitro and in vivo anti-breast cancer activity of "Njansang" seed oil. The inhibitory effect of "Njansang" seed oil was determined using MTT and CCK-8 dye reduction assays. Breast cancer was induced with DMBA and promoted with E2V (1mg/kg) for 4weeks in ovariectomized rats (menopausal condition). Evaluated parameters included tumor incidence, tumor mass and volume, histopathology, breast cancer biomarker CA 15-3, antioxidant status (CAT, GSH, MDA, NO, SOD), TNF-α and INFγ levels, lipid profile (total cholesterol, LDL-cholesterol, triglycerides and HDL-cholesterol), as well as toxicity parameters (ALT, AST, creatinine). "Njansang" oil significantly reduced the growth of ER+ (MCF-7) and triple negative (MDA-MB 231) adenocarcinoma cells in vitro as well as tumor incidence, tumor mass and CA 15-3 levels in vivo. It exhibited antioxidant activity, characterized by an increase in SOD and catalase activities, GSH levels and decreased MDA levels compared to the DMBA group. TNF-α and INF-γ levels were reduced following oil treatment, while total cholesterol, LDL-cholesterol and triglyceride levels were reduced. The aforementioned findings confirm the protective effects of"Njansang"oil on induced breast cancer in ovariectomized rats.

Assessments of anti-breast cancer activity and profiling of active compounds using LC-MS/MS from the Indonesian Agelas nakamurai

Breast cancer is now one of the leading causes of death in women worldwide. Finding a cure is, therefore, critical for women’s health. Marine sponge-derived drugs have gained interest in breast cancer treatment. The development of marine natural products into cancer therapy includes several stages. It starts with the screening using the cytotoxic test method, a preclinical trial using the animal mode, and clinical trial phases I and II. In this study, we focus on the basic cytotoxic test to find the new source of anti-breast cancer compounds derived from Agelas nakamurai to know the potential for further investigation to become lead compounds. However, the anti-breast cancer potential of the Indonesian marine sponge A. nakamurai has never been studied. This study aimed to evaluate the anti-breast cancer potential of extract and fraction of A. nakamurai against epithelial human breast cancer cells (MDA-MB-231 and MCF-7 cells line) and to preliminary profile the known active compounds. The maceration using methanol was used for extraction and followed by partitioning with varied solvents [ethyl acetate (EtOAc), butanol, and water]. Fractionation was done using normal phase open column chromatography, and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) was used for analyzing compounds. MDA-MB-231, MCF-7, and HEK-293 cell lines were used for biological activities. The chromatographic separation of the EtOAc fraction led to the F7 subfraction which strongly inhibits proliferation against the MDA-MD-231 (IC50: 10.677 μg/mL), MCF-7 (IC50: 15.154 μg/mL), and HEK-293 cells line. The LC-MS/MS data of active fraction F7 contained gelatin-D and ageloxime-D. This study reported that fraction 7 of A. nakamurai showed strong activity against MDA-MB-231, MCF-7, and HEK-293 cell lines. Further analysis will be carried out to know the mechanisms of action of active compounds.

Design and Synthesis of New bis-oxindole and Spiro(triazole-oxindole) as CDK4 Inhibitors with Potent Anti-breast Cancer Activity.

Since CDKs have been demonstrated to be overexpressed in a wide spectrum of human malignancies, their inhibition has been cited as an effective technique for anticancer drug development. In this context, new bis-oxindole/spiro-triazole-oxindole anti-breast cancer drugs with potential CDK4 inhibitory effects were produced in this work. The novel series of bis-oxindole/spirotriazole- oxindole were synthesized from the reaction of bis-oxindole with the aniline derivatives then followed by 1,3-dipolar cycloaddition of hydrazonoyl chloride. The structure of these bis-oxindole/spiro-triazole-oxindole series was proven based on their spectral analyses. Most bis-oxindole and bis-spiro-triazole-oxindole compounds effectively inhibited the growth of MCF-7 (IC50 = 2.81-17.61 μM) and MDA-MB-231 (IC50 = 3.23-7.98 μM) breast cancer cell lines with low inhibitory activity against normal WI-38 cells. While the reference doxorubicin showed IC50 values of 7.43 μM against MCF-7 and 5.71 μM against the MDA-MB-231 cell line. Additionally, compounds 3b, 3c, 6b, and 6d revealed significant anti-CDK4 activity (IC50 = 0.157- 0.618 μM) compared to palbociclib (IC50 = 0.071 μM). Subsequent mechanistic investigations demonstrated that 3c was able to trigger tumor cell death through the induction of apoptosis. Moreover, it stimulated cancer cell cycle arrest in the G1 phase. Furthermore, western blotting disclosed that the 3c-induced cell cycle arrest may be mediated through p21 upregulation. According to all of the findings, bis-oxindole 3c shows promise as a cancer treatment targeting CDK4.

Design, 3D-QSAR, molecular docking, ADMET, molecular dynamics and MM-PBSA simulations for new anti-breast cancer agents

Breast cancer is the most frequent form of malignant tumor in women, and represents a major public health problem due to its high mortality rate. Although a multitude of therapeutic options exist for control of this disease, the emergence of resistance to current pharmaceutical treatments underscores the urgency of developing new anti- breast cancer drugs, with a focus on reducing the adverse effects associated with current therapeutic agents. The present study concerns a new series of (23) compounds based on 1,4-quinone and quinoline derivatives to design candidate drugs against breast cancer. For this purpose, integrated computational techniques were applied, including 3D-QSAR, molecular docking and molecular dynamics simulations (MD). CoMFA and CoMSIA were used to build a robust and highly reliable 3D-QSAR models. To validate the model's predictive capabilities, an external validation was carried out. The results of the best model (CoMSIA/SEA) revealed that electrostatic, steric and hydrogen bond acceptor fields had a significant effect on the anti-breast cancer activity of molecules studied. In addition, evaluation of ADMET properties determined whether these newly designed ligands were likely to be selected as drug-candidates. To confirm the binding stability of the selected ligands to aromatase (3S7S) and validate the molecular docking results, molecular dynamics simulations lasting 100 nanoseconds were performed by calculating RMSD, RMSF, RoG, H-bond, SASA and MM-PBSA parameters. As a result, only one designed compound (ligand 5) emerged as the most promising drug candidate for experimental in vitro and in vivo testing, due to its potential inhibition of breast cancer.

Unveiling the cytotoxic and anti-proliferative potential of green-synthesized silver nanoparticles mediated by Colletotrichum gloeosporioides.

Fungal endophytes are a putative source of bioactive metabolites that have found significant applications in nanomedicine due to their metabolic versatility. In the present study, an aqueous extract of the fungal endophyte, Colletotrichum gloeosporioides associated with a medicinal plant Oroxylum indicum, has been used for the fabrication of green silver nanoparticles (CgAgNPs) and further evaluated their cytotoxic and anti-proliferative activity. Bioanalytical techniques including UV-Vis spectral analysis revealed a sharp band at 435 nm and functional molecules from the aqueous extract involved in the synthesis of CgAgNPs were evidenced through FTIR. Further, the crystalline nature of CgAgNPs was determined through XRD analysis and microscopy techniques including AFM, TEM and FESEM demonstrated the spherical shape of CgAgNPs exhibiting a crystalline hexagonal lattice and the size was found to be in the range of 9-29 nm. The significant cytotoxic potential of CgAgNPs was observed against breast cancer cells, MDA-MB-231 and MCF-7 with IC50 values of 18.398 ± 0.376 and 38.587 ± 1.828 μg mL-1, respectively. The biochemical study revealed that the treatment of MDA-MB-231 and MCF-7 cells with CgAgNPs reduces glucose uptake, suppresses cell proliferation, and enhances LDH release, indicating reduced cell viability and progression. Moreover, our research revealed differential expression of genes associated with apoptosis, cell cycle inhibition and metastasis suppression, evidencing anti-proliferative activity of CgAgNPs. The main objective of the present study is to harness anti-breast cancer activity of novel biogenic nanoparticles synthesized using the aqueous extract of O. indicum associated C. gloeosporioides and study the underlying mechanistic pathway exerted by these mycogenic nanoparticles.

Sulfated polysaccharides of Laetiporus sulphureus fruiting bodies exhibit anti-breast cancer activity through cell cycle arrest, apoptosis induction, and inhibiting cell migration

Ethnopharmacological relevanceLaetiporus sulphureus has long been used as an edible and medicinal mushroom in Asia, America, and Europe. Its fruiting bodies are widely used in folk medicine for treating cancer, gastric diseases, cough, and rheumatism. Polysaccharides are an important bioactive component of mushrooms. In nature, sulfated polysaccharides have never been reported in mushrooms. Furthermore, there is no information on differences in physicochemical properties and anti-breast cancer activities between polysaccharides (PS) and sulfated polysaccharides (SPS) of L. sulphureus. Aim of the studyThis study aimed to investigate the physicochemical properties of PS and SPS isolated from fruiting bodies of L. sulphureus and examine their anti-proliferative effects and mechanism(s) of action on MDA-MB-231 breast cancer cells. MethodsPolysaccharides (PS) were isolated using hot water and ethanol precipitation methods. Sulfated polysaccharides (SPS) were isolated by the papain-assisted hydrolysis method. Physicochemical properties comprising sugar, protein, uronic acid, and sulfate contents, and molecular weight, monosaccharide composition, and structural conformation were analyzed on PS and SPS. In the anti-cancer study, a triple-negative breast cancer cell line (MDA-MB-231) and a normal human mammary epithelial cell line (H184B5F5/M10) were used to evaluate the anti-proliferative activity of PS and SPS, and their mechanism(s) of action. ResultsThe results showed that SPS, which had higher sulfate and protein contents and diversified monosaccharide composition, exhibited more potent anti-proliferative activity against MDA-MB-231 cells than PS. Furthermore, it had a selective cytotoxic effect on breast cancer cells but not the normal cells. SPS induced cell cycle arrest at G0/G1 phase via down-regulating CDK4 and cyclin D1 and up-regulating p21 protein expression. Breast cancer cell apoptosis was not observed until 72 h after SPS treatment. In addition, SPS also markedly inhibited breast cancer cell migration. ConclusionThis study demonstrates that SPS exhibited selective cytotoxicity and was more potent than PS in inhibiting MDA-MB-231 cell proliferation. The contents of sulfate and protein, and monosaccharide composition could be the main factors affecting the anti-breast cancer activity of L. sulphureus SPS.

Design, synthesis, and evaluation of 4-(3-(3,5-dimethylisoxazol-4-yl)benzyl)phthalazin-1(2H)-one derivatives: potent BRD4 inhibitors with anti-breast cancer activity

BRD4 inhibitors have demonstrated promising potential in cancer therapy. However, their therapeutic efficacy in breast cancer varies depending on the breast cancer subtype, particularly in the treatment of TNBC. In this study, we designed and synthesized 94 derivatives of 4-(3-(3,5-dimethylisoxazol-4-yl)benzyl)phthalazin-1(2H)-one to evaluate their inhibitory activities against BRD4. Notably, compound DDT26 exhibited the most potent inhibitory effect on BRD4, with an IC50 value of 0.237 ± 0.093 μM. DDT26 demonstrated significant anti-proliferative activity against both TNBC cell lines and MCF-7 cells. Intriguingly, the phthalazinone moiety of DDT26 mimicked the PAPR1 substrate, resulting in DDT26 displaying a moderate inhibitory effect on PARP1 with an IC50 value of 4.289 ± 1.807 μM. Further, DDT26 was shown to modulate the expression of c-MYC and γ-H2AX, induce DNA damage, inhibit cell migration and colony formation, and arrest the cell cycle at the G1 phase in MCF-7 cells. Our findings present potential lead compounds for the development of potent anti-breast cancer agents targeting BRD4.

Zerumbone (ZER), a Potential Anticancer for Breast Mediates Cancer Cell Death Through Targeting β-catenin Signaling Pathway in MCF-7 Cell Line

Background: Zerumbone is a sesquiterpene which was found to delay progression of breast cancer through apoptosis induction via up-regulating Bax protein and down-regulating Bcl2 protein. Purpose: In this study, we aimed to investigate Zerumbone, a natural compound of medicinal herbal plant isolated from Zingiber zerumbet, for anti-cancer activity against MCF-7 cell line. Methods: Human cancer cell lines of breast MCF-7 cells were obtained from American Type Culture Collection (ATCC, Manassas, VA). ON target plus smart pool siRNA, the most efficient method is used for preparation of β-catenin siRNA. Cyclophilin B siRNA is considered as positive control. Zrumbone is an ethanol-soluble compound isolated from Zingiber zerumbet, extracted by the hydro-distillation (steam distillation) method. Purification of ZER was examined using HPLC. The MCF-7 cells transfected with 100 µM human β-catenin (CTNNB1) siRNA or cyclophilin B siRNA positive control. After transfection, the cells were harvested at 48hrs for mRNA analysis or 48 – 72 hrs for protein analysis. IC50 for ZER was determined using MTT assay. MCF-7 transfected with β-catenin siRNA were then treated with ZER IC50. The mRNA expression was analyzed using real-time to ensure the knock down of β-catenin. TUNNEL assay was used to confirm apoptosis and flow cytometry was applied for quantification of apoptotic cells. Western blot analysis was done to evaluate the effect of ZER and β-catenin (CTNNB1) siRNA on the expression of β-catenin and its functional impact on the proliferation and survival of MCF-7 cells. Results: ZER decreased β-catenin protein expression in breast cancer cell lines. ZER downregulated β-catenin mRNA level in breast cancer cell lines. Depletion of β-catenin by β-catenin siRNA and ZER induce cell apoptosis. Apoptosis caused by ZER was confirmed/examined using by annexin V (annexin V was used as a marker for drug action). Conclusion: Zerumbone possesses anti-breast cancer activity, which could be attributed to the reduction of β-catenin protein expression in MCF-7 breast cancer cell lines, downregulation of β-catenin mRNA level in breast cancer cell lines and through annexin V.

Effect of variables on exemestane-loaded albumin nanoparticles: statistical optimization and anti-cancer activity in MCF-7 cell lines

This research aimed to evaluate the effect of variables on exemestane-loaded bovine serum albumin nanoparticles (EXE-BSA NPs) to improve anti-breast cancer activity. EXE-BSA NPs were optimized using 32 factorial design, wherein the concentration of BSA (X 1) and sonication time (X 2) were independent variables and particle size (Y 1) and %w/w entrapment efficiency (Y 2) were dependent variables. The statistical optimization revealed a significant effect of BSA concentration on both variables, whereas sonication time affected only particle size. The optimized EXE-BSA NPs were spherical with 124.1 ± 2.62 nm particle size, 83.95 ± 1.06% w/w drug entrapment, and exhibited a biphasic release of 100% (w/w) drug over 72 h. The optimized formulation induced cytotoxicity in MCF-7 cell lines with an IC50 value of 21.46 µg/mL by MTT assay, almost half the free drug (54.87 µg/mL). Thus, statistically optimized EXE-BSA NPs were effective in MCF-7 cell lines and can be explored to treat estrogen receptor-positive breast cancer.

Antibreast cancer activities of phytochemicals from Anonna muricata using computer-aided drug design (CADD) approach

Abstract Antibreast cancer activities of 131 phytochemicals from Annona muricata (Soursop) were investigated against human placental aromatase (PDB ID: 3S7S), a prominent target receptor in breast cancer therapy using computer aided-drug design approach. An antibreast cancer drug (tamoxifen) was used for comparison. The result of this work flourishes caffeoquinic acid (−8.4 kcal/mol), roseoside (−8.3 kcal/mol), chlorogenic acid (−8.2 kcal/mol), feruloylglycoside (−8.1 kcal/mol), citroside A (−8.0 kcal/mol), and coreximine (−7.8 kcal/mol), as probable inhibitors of human placental aromatase. This is due to their excellent binding affinities (ΔG), coupled with outstanding druglike, absorption, distribution, metabolism, excretion, and toxicity profiles, bioavailability and oral-bioavailability properties, and the interactions of important residues with the active pocket of human placental aromatase. All the results obtained were similar to that of the standards tamoxifen (−8.0 kcal/mol) but could be better when optimized. Thus, lead optimization, molecular dynamics, and in vivo investigations are thereby recommended on the identified potent compounds in the quest of developing new therapeutic agents against breast cancer.

Selaginellin derivatives from Selaginella tamariscina and evaluation for anti-breast cancer activity

A phytochemical investigation of Selaginella tamariscina led to the isolation of 17 selaginellin derivatives. Their inhibitory activities against breast cancer cells were screened, and preliminary structure-activity relationships were also established. Among them, dimeric selaginellin 17 showed potential activity against MDA-MB-231 cells with an IC50 value of 3.2 ± 0.1 μM, corresponding to 4-fold higher potency than the reference compound 5-FU (IC50 14.8 ± 0.2 μM). Mechanistic studies indicated that 17 could cause G2/M phase arrest in MDA-MB-231 cells and induce apoptosis accompanied by increased ROS levels.

Development of Statistically Optimized Piperine-Loaded Polymeric Nanoparticles for Breast Cancer: In Vitro Evaluation and Cell Culture Studies.

Piperine (PPN) is a natural alkaloid derived from black pepper (Piper nigrum L.) and has garnered substantial attention for its potential in breast cancer therapy due to its diverse pharmacological properties. However, its highly lipophilic characteristics and poor dissolution in biological fluids limit its clinical application. Therefore, to overcome this limitation, we formulate and evaluate PPN-encapsulated polycaprolactone (PCL) nanoparticles (PPN-PCL-NPs). The nanoparticles were prepared by a single-step nanoprecipitation method and further optimized by a formulation design approach. The influence of selected independent variables PCL (X1), poloxamer 188 (P-188; X2), and stirring speed (SS; X3) were investigated on the particle size (PS), polydispersity index (PDI), and % encapsulation efficiency (EE). The selected optimized nanoparticles were further assessed for stability, in vitro release, and in vitro antibreast cancer activity in the MCF-7 cancer cell line. The PS, PDI, zeta potential, and % EE of the optimized PPN-PCL-NPs were observed to be 107.61 ± 5.28 nm, 0.136 ± 0.011, -20.42 ± 1.82 mV, and 79.53 ± 5.22%, respectively. The developed PPN-PCL-NPs were stable under different temperature conditions with insignificant changes in their pharmaceutical attributes. The optimized PPN-PCL-NPs showed a burst release for the first 6 h and later showed sustained release for 48 h. The PPN-PCL-NPs exhibit exceptional cytotoxic effects in MCF-7 breast tumor cells in comparison with the native PPN. Thus, the formulation of PPN-loaded PCL-NPs can be a promising approach for better therapeutic efficacy against breast cancer.

Development of Gefitinib-Loaded Solid Lipid Nanoparticles for the Treatment of Breast Cancer: Physicochemical Evaluation, Stability, and Anticancer Activity in Breast Cancer (MCF-7) Cells.

In the current study, the toxic effects of gefitinib-loaded solid lipid nanoparticles (GFT-loaded SLNs) upon human breast cancer cell lines (MCF-7) were investigated. GFT-loaded SLNs were prepared through a single emulsification-evaporation technique using glyceryl tristearate (Dynasan™ 114) along with lipoid® 90H (lipid surfactant) and Kolliphore® 188 (water-soluble surfactant). Four formulae were developed by varying the weight of the lipoid™ 90H (100-250 mg), and the GFT-loaded SLN (F4) formulation was optimized in terms of particle size (472 ± 7.5 nm), PDI (0.249), ZP (-15.2 ± 2.3), and EE (83.18 ± 4.7%). The optimized formulation was further subjected for in vitro release, stability studies, and MTT assay against MCF-7 cell lines. GFT from SLNs exhibited sustained release of the drug for 48 h, and release kinetics followed the Korsmeyer-Peppas model, which indicates the mechanism of drug release by swelling and/or erosion from a lipid matrix. When pure GFT and GFT-SLNs were exposed to MCF-7 cells, the activities of p53 (3.4 and 3.7 times), caspase-3 (5.61 and 7.7 times), and caspase-9 (1.48 and 1.69 times) were enhanced, respectively, over those in control cells. The results suggest that GFT-loaded SLNs (F4) may represent a promising therapeutic alternative for breast cancer.

Network pharmacology-based approach to investigate the molecular targets of essential oil obtained from lavender for treating breast cancer

Lavender essential oil (LEO) is known for its medicinal use in the development of pharmaceuticals. Further investigations were demonstrated that LEO has many biological properties including apoptosis. However, The anti-breast cancer activity and mechanism of LEO are still unclear. we aim to elucidate the elusive anti-breast cancer activity and mechanism of LEO by unveiling the intricate molecular targets that it engages with, thereby priming it for effective therapeutic intervention against breast carcinoma. In this paper, we extracted LEO from lavender and analyzed it's chemical constituents by using hydro-distillation and gas chromatography-mass spectrometry (GS-MS/MS) method, respectively. The active components against breast cancer and it's molecular targets were selected and biological process, molecular function, cellular component and involving pathways were evaluated via network pharmacology approach. Cell viability, apoptosis and cell cycle assay were used to evaluate anti-breast cancer effect of LEO. Employing the western blotting method to validate target protein expression following LEO treatment in vitro. We found the 21 effective components and 213 drug-disease common targets of LEO. Amoung them, 7 active components and 19 targets were identified as potential therapeutic targets. Gene ontology results revealed that the drug-disease common targets of LEO were mainly distributed in membrane region, involved in peptide-tyrosine phosphorylation, and primarily associated with protein tyrosine kinase. We also found that drug-disease common targets might contribute to the regulation of PI3K-AKT signaling pathway by using KEGG pathway analysis. Besides, our study demonstrated reduced cell viability, induced apoptosis in MCF-7 and MDA-MB-231 treated with LEO while cell cycle arrest was not altered. The AKT1 expression down-regulated while PIK3CA expression was increased in both cell lines. Our findings indicate that LEO has the ability to induce apoptosis by modulating the expression of PI3K-AKT signaling pathway in these cell lines.