Anti-breast Cancer Research Articles

Evaluation of cytotoxic potential of silver nanoparticles biosynthesized using essential oils of Jasminum sambac against breast cancer and bacterial cells.

Essential oils (EOs) which cover about 91% whole biomolecules formulated from Jasminum sambac leaves based on Gas chromatography-mass spectrometry were employed to identify structures. EOs were observed as good agents in the preparation of Silver nanoparticles (AgNPs) through the proposed mechanism that was attempted to interpret the pathway of the bio-preparation process. The characterization of EOs-AgNPs carried via ultraviolet-visible to reveal surface plasmon resonance at 420nm, Fourier transform infrared to observe functional groups EOs compared to EOs-AgNPs. X-ray diffraction (XRD) revealed a broad chart owing to the small size of AgNPs in average size less than 10nm calculated relying on image J software, spherical AgNPs with a small dispersive size observed by transmission electron microscopy. Quasi near spherical surface morphology of EOs-AgNPs had detected by field emission scanning electron microscope. EOs-AgNPs were assessed for their antibacterial potential against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria as suppressing bacterial agents. EOs-AgNPs had their anti-breast cancer MCF-7 cell line ability investigated by DNA fragmentation; cycle flow cytometry (apoptosis) at half maximal inhibitory concentration (IC50) was determined at 260µg/mL which has been stated by cytotoxicity (MTT) assay. EOs-AgNPs have antibacterial and anticancer therapeutic potential, and it is safe, inexpensive, and scalable in the nanoscale range.

2-(1H-indol-3-yl)ethyl]-(4-nitrobenzylidene)amine: Investigating the inhibition of breast cancer: Synthesis, structure, in-silico–Computational predictions & potent antibacterial properties

The synthesis and characterization of a novel Schiff base compound, [2-(1H-indol-3-yl)ethyl]-(4-nitrobenzylidene)amine (2IE4NBA), are described and characterized by 1H, 13C NMR, FT-IR, and UV–VIS spectroscopic analysis. The crystal structure was determined by monoclinic space group P21/c, with lattice parameters a = 15.8372(8) Å, b = 11.0720(5) Å, c = 8.5464(4) Å, β = 97.780(2) °, and Z = 4. The intermolecular interactions in the Schiff base 2IE4NBA were theoretically examined by Hirshfeld surface analysis. The optimized structure, HOMO and LUMO energy gap, mulliken population analysis, and molecular Electrostatic Potential (MEP) of the compound were calculated by Density Functional Theory (DFT) calculation with the B3LYP/6–311 G basis set method. In addition, we compared calculated and experimental spectral values. Molecular docking studies indicated that the synthesized compound, 2IE4NBA, interacts with the binding pocket of mutated TP53 with a binding affinity of -8.0 kcal/mol. The docking results demonstrated favourable molecular-level interactions with the anticancer drug target, exhibiting strong interactions with active site residues. In vitro studies revealed that the compound exhibited the best minimum inhibitory concentration (MIC) value against Staphylococcus aureus and demonstrated an effect on MDA-MB-231 cancer cell lines. This study investigated its potential as a breast cancer therapeutic agent. 2IE4NBA exhibited promising anti-breast cancer activity against the MDA-MB-231 breast cancer cell line, as confirmed by MTT assay.

Synthesis, molecular docking, and anti-breast cancer study of 1-H-indol-3-Carbohydrazide and their derivatives

A prominent heterocyclic system found in medications and natural goods is indoles. Due to the significance of this important ring system, a fresh batch of unique indole derivatives was created using indole carbohydrazide. The triazole moiety of indole derivative (3) is produced by reacting carbohydrazide with carbon disulfide in alkaline conditions, followed by hydrazine treatment. In addition to synthesizing additional derivatives, indole-bearing triazole (3) was condensed with aromatic aldehydes to create the indole derivatives (4a–c). Mass spectra, 1HNMR, 13CNMR, and infrared spectroscopy were used to diagnose all produced derivatives. An MTT assay was employed to test the derivatives against MCF-7 cells. The findings demonstrated the inhibitory action of compounds 5a and 5b, with IC50 values of 42.6 ± 0.33 µM and 27.3 ± 0.28, respectively. Affinity energy and the interaction between the investigated chemicals and receptor (CDK4 ID: 2w96) were ascertained by studying molecular docking. The chemical structure-physicochemical-pharmacokinetic relationship provides useful insight for medicinal chemists to design indole-triazole derivatives with acceptable drug-like and pharmacokinetic properties.

Evaluation of the anti-breast cancer properties of Origanum majorana aqueous extract green-mediated nanoparticles

This research details the synthesis of biogenic silver nanoparticles utilizing Origanum majorana as a supporting material. The leaves of the plant served as a natural reducing agent and a proficient stabilizer for the generated silver nanoparticles (Ag NPs). The formulated NPs were analyzed through the analysis of their physicochemical properties utilizing UV–Vis, FT-IR, and FE-SEM techniques. The investigation of the antioxidant characteristics of the Ag NPs was followed using the DPPH assay. The results revealed that the silver nanoparticles exhibited considerable antioxidant activity, as evidenced by the IC50 value. Recent findings suggest that the effectiveness of nanoparticles in treating human breast cancer can be linked to their antioxidant characteristics. An evaluation was followed on the ability of biologically synthesized Ag NPs to combat breast cancer in various cell lines. The silver nanoparticles exhibited significant anti-breast cancer properties, successfully eradicating the MCF10 cancer cell line in a manner that was influenced by both time and concentration, as assessed through the MTT assay. Ag NPs facilitate cell apoptosis, a process linked to elevated levels of pro-apoptotic markers, including Bax and cleaved caspase-8, while concurrently reducing the concentration of the anti-apoptotic marker Bcl-2. Furthermore, silver nanoparticles exhibit a decrease in colony formation in comparison to the respective control group. The examination of molecular pathways in cells exposed to Ag NPs revealed a significant elevation in p53 expression, coupled with a decrease in both total and phosphorylated levels of Signal Transducer and Activator of Transcription 3 (STAT3) in the studied cell lines. This suggests that p53 and STAT3 play essential roles in the biological responses triggered by the extract in human breast cancer cells.

Spectroscopic, computational, docking, and cytotoxicity investigations of 5-chloro-2-mercaptobenzimidazole as an anti-breast cancer medication

The vibrations were attributed to 5-chloro-2-mercaptobenzimidazole using FTIR and FT-Raman spectroscopy. The optimized geometrical parameters, IR intensity, and the Raman activity of the vibrational bands were estimated using the Becke three-parameter Lee-Yang-Parr functional and the 6-311++G(d,p) level of theory. These findings are compared with the experimental data. The molecule’s HOMO-LUMO energy gap is found to be 4.418 eV. UV-Vis analysis reveals that the π→π* transition, which happens when electron density shifts from nitrogen, sulfur, and chlorine atoms in the molecule, to the electrons of the C-C bonds of the ring. Total density of states was used to assess the molecular orbital contributions. There are 47α and 47β electrons totaling 94 electrons in the DOS spectrum. NBO investigations indicate that a considerable stabilizing energy of 30.37 and 30.90 Kcal/mol was revealed by the lone pair transition of N1 and N3 atoms to π*(C7-C8) and π*(C4-C9). The more electrophilic region, as seen by the red zone in MEP mapping, lies in the vicinity of the nitrogen and sulfur atoms. The molecule’s hydrogen atoms are found in the blue nucleophilic area. The theoretical chemical shifts for 1H and 13C NMR ranged from 7.03 to 8.23 ppm and 113.10 to 207.31 ppm, respectively. The docking research showed that the molecule attached to protein 1AQU with a greater binding energy of −6.8 Kcalmol−1. The cytotoxicity of the sample was evaluated against a MCF-7 cell line (IC50 = 16.54 µg/ml) and exhibited a good breast cancer action. In addition, ADMET prediction has been used to estimate the medicinal applicability of the chemical.

The Antibacterial and Anti-Breast Cancer Activities of Caulerpa racemosa from the Minahasa Peninsula Water and North Sulawesi, Indonesia

The Antibacterial and Anti-Breast Cancer Activities of Caulerpa racemosa from the Minahasa Peninsula Water and North Sulawesi, Indonesia

High β-sitosterol-D-glucoside content in sweet potato varieties and its anti-breast cancer potential through multiple metastasis-associated signals

β-Sitosterol-D-glucoside (β-SDG) is a phytosterol compound whose antitumor activity has been confirmed by previous studies. However, its suppression on breast cancer remains unclear. To that purpose, we isolated β-SDG from sweet potato and investigated the breast-cancer-inhibiting mechanism using proteomic analysis. The sweet potato species S6 with high β-SDG content were chosen form 36 species and β-SDG was isolated by HPLC. Afterwards, an in situ animal model of breast cancer was established, and β-SDG significantly reduced the tumor volume of MCF-7 xenograft mice. Proteomic analysis of tumor tissues revealed that 127 of these proteins were upregulated and 80 were downregulated. Gene ontology and network analysis showed that regulatory proteins were mainly associated with epithelial-mesenchymal transition (EMT), myogenesis, cholesterol homeostasis, oxidative phosphorylation and reactive oxygen pathways, while Vimentin, NDUF, VDAC1, PPP2CA and SNX9 were the most significant 5 node degree genes. Meanwhile, in vitro and in vivo results showed that the protein expression of PPP2CA and Vimentin, which are markers of EMT, were involved in breast cancer cell metastasis and could be reversed by β-SDG. This work highlights β-SDG as a bioactive compound in sweet potato and the potential therapeutic effect of β-SDG for the treatment of breast cancer by inhibiting metastasis.

Unveiling the Therapeutic Potential of Paclitaxel Combinations Against Breast Carcinoma and Identification of InVivo Biomarkers.

Breast cancer (BC) is one of the leading causes of high mortality rates in women worldwide. Although advancements have been made in the design of therapeutic strategies and drug discovery, drug resistance remains one of the key challenges. One of the ways to overcome drug resistance is finding potential drug combinations since the efficacy of combined drugs is higher than their individual efficacies if the combination is a synergistic pair. Therefore, the current study uses a BC patient-derived xenograft (PDX) dataset to evaluate the effects of various cancer drugs on breast cancer invivo models. The drug effects are further validated by four machine learning models, namely Elastic Net, Least Absolute Shrinkage and Selection (LASSO), Support Vector Machine (SVM), Random Forests (RF), as well as exploring the shortlisted drugs in combination with paclitaxel, a baseline drug for enhanced efficacy on tumor volume reduction. Additionally, the study also shortlists the top 50 invivo biomarkers correlated with the effects of the drugs. The outcomes could be significantly important for the design of an effective anti-breast cancer therapy.

Development of New N- and S-substituted-imidazolidin-4-one Analogues with Potent Anti-breast Cancer Activity: In vitro Molecular Docking Assessment

: 2-Thioxoimidazolidin-4-one derivatives 3, 4, 7, 8, and 9 have been synthesized from 3- (benzylideneamino)-2-thioxoimidazolidin-4-one (2) as a starting material. Compounds 3, 4, 7, 8, and 9 were obtained via the reaction of compound (2) with ethyl chloroacetate, methyl acrylate, and chlorophenacyl bromide, respectively. Elemental analysis and several spectroscopy techniques were used to confirm the synthesized compounds. The synthesized compounds, particularly compounds 7 and 8, exhibited significant cytotoxic influences on MCF-7 cells, surpassing staurosporine. Compounds 7 and 8 can induce apoptosis in those treated MCF-7 cells. Studying molecular docking approved that compounds 7 and 8 bind in two and three dimensions to the aromatase binding pockets. Molecular modeling indicates compounds 7 and 8 have a strong affinity for human topoisomerase II beta, establishing its promise as a multifaceted antitumor agent for breast cancer.

Improving Water Solubility and Skin Penetration of Ursolic Acid through a Nanofiber Process to Achieve Better In Vitro Anti-Breast Cancer Activity.

Woman's breast cancer has always been among the top ten causes of cancer death, and nearly 2% to 5% of locally advanced breast cancers develop a fungating breast wound. Fungal breast cancer leads to skin ulcers, wound ruptures, and other bacterial infections in patients. Ursolic acid (UA), a natural pentacyclic triterpene compound, is widely distributed in many fruits. Previous studies demonstrated that UA has anti-breast cancer, antifungal, and improved wound-healing effects. UA, however, had poor water solubility and low bioavailability, restricting its clinical application. Nanofibers have the advantages of rapid dissolution, improved stability, and bioavailability of active ingredients. We had successfully prepared ursolic acid nanofibers (UANFs) and effectively improved their water solubility and skin penetration. UANFs can increase water solubility by improving the physicochemical properties, including increased surface area, intermolecular bonding with excipients, and amorphous transformation. Furthermore, UANFs had better anti-breast cancer activity than raw UA. UANFs inhibited the expression of phospho-signal transducer and activator of transcription 3 (STAT3) and phospho-extracellular regulated protein kinases (ERK)1/2, and induced cleaved caspase-3 protein expression, but had no effect on the raw UA treatment. In summary, UANFs enhanced the skin absorption of UA and improved its anti-breast cancer efficacy. We expect that UANFs can be used as an anti-breast cancer treatment and reduce the discomfort of breast cancer patients during dressing changes, but more detailed efficacy and safety trials still need to be conducted in further studies.

Screening of Anti-breast Cancer and Anti-oxidant Potentials of Selected Medicinal Plants from Sri Lanka

Screening of Anti-breast Cancer and Anti-oxidant Potentials of Selected Medicinal Plants from Sri Lanka

Synthesis of silver nanoparticles embedded into melamine polyaminal networks as antibacterial and anticancer active agents

Silver nanoparticles were successfully incorporated into a melamine-based polymer, resulting in the synthesis of (Ag NPs@Bipy-PAN) through a reverse double solvent approach. The synthesised Ag NPs@Bipy-PAN polymer underwent extensive characterisation through Powder X-ray Diffraction (PXRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy and Energy Dispersive X-ray (EDX) and Thermal Gravimetric Analysis. PXRD analysis confirmed the successful encapsulation of Ag nanoparticles and provided insights into the amorphous nature of the polymer following encapsulation. SEM and EDX analyses further corroborated the presence and distribution of Ag nanoparticles on the polymer surface. The biological efficacy of the Ag NPs@Bipy-PAN polymer was evaluated through antibacterial, anti-breast cancer, and biocompatibility assays. The results demonstrated notable antibacterial and anticancer activities, with significant efficacy against bacterial strains and breast cancer cells. Biocompatibility assessments indicated acceptable compatibility, particularly at a concentration of 2.5 mg/mL, compared to untreated control cells. These findings suggest that Ag NPs@Bipy-PAN has considerable potential as a candidate for cancer-targeted and antimicrobial drug delivery systems. The incorporation of silver nanoparticles into the melamine-based polymer enhances the safety profile of these systems in in vivo conditions, making them a viable option for advanced therapeutic applications.

Synthesis of N-[trisubstitutedphenyl]-4-methyl Aniline Derivatives as Novel Anti-Breast Cancer Agents

A series of N-(substituted)-4-methyl aniline derivatives (4a,b, 5a,b, 6, 7, 8, and 9) has been designed and synthesized, and their biological activities were also evaluated as potential anti-tumor and tubulin enzyme inhibitors. Among all compounds, compound (8) showed the most potent tubulin aromatase enzyme inhibitory activity in vitro with an IC50 of 157.3 pg/mL compared to the reference inhibitor Dox (IC50 = 227.4 pg/mL). A docking simulation was performed to insert compound (8) into the crystal structure of human aromatase at the active site to determine the probable binding model. Based on the previous results, compound (8) with potent inhibitory activity on tumor growth could be employed as a potential anticancer agent.

Identification and Analysis of Potential Breast Anticancer Agents in Pogostemon Cablin through Network Pharmacology

Breast cancer is one of the highest known causes of death in Indonesia, especially for women. Pogostemon cablin Benth is one of the Aceh's endemic herbal plants that has been studied to have potential such as anti-inflammatory, antiproliferative, antioxidant, antimicrobial, and proapoptotic. Network pharmacology approach was conducted to explore and analyze the potential of P. cablin as an anti-breast cancer. P. cablin plant compounds were obtained from GCMS and breast cancer genes data were obtained from OMIM, GeneCard, and DisGeNet databases. Target proteins and pathways involved were identified using STRING-DB and Metascape. Network analysis was performed using Cytoscape. A total of 65 plant compounds with 554 target proteins and 1854 disease genes were obtained. Based on the results of combining protein targets using Venn diagrams, 138 overlapping proteins between drug compounds and breast cancer disease targets were identified. Based on KEGG and GO analysis, P. cablin is known to have potential in breast cancer treatment/therapeutic mechanisms. Based on the "compound-protein target-pathway" multi-target mechanism, pogostol; 1H-Cycloprop[e]azulen-7-ol, decahydro-1,1,7-trimethyl-4-methylene-, [1ar-(1aα,4aα,7β,7aβ,7bα)]-; 3-Hexen-1-ol, 2,5-dimethyl-, acetate, (Z)-, 5β,7βH,10α-Eudesm-11-en-1α-ol; Acetic acid, 3-hydroxy-6-isopropenyl-4,8a-dimethyl 1,2,3,5,6,7,8,8a-octahydronaphthalen-2-yl ester; and Humulenol-II interacts with proteins that play a significant role in breast cancer, which are MAPK1, EGFR, TNF, AKT1, and JAK2. Hence, it can be concluded that P. cablin has good potential to be a source of therapeutic treatment against breast cancer. However, it needs to be tested clinically to further determine the effects of this P. cablin compound.

Synthesis, anticancer, α-glucosidase inhibition, molecular docking and dynamics studies of hydrazone-Schiff bases bearing polyhydroquinoline scaffold: In vitro and in silico approaches

A series of hydrazone-Schiff base derivatives of polyhydroquinoline (PHQ) nucleus have been synthesized, structurally deduced by NMR (13C- and 1H-) and HR-ESI-MS spectroscopic methods and finally subjected for anti-cancer and α-glucosidase inhibitory activities. The MTT assay's results exposed that these eight compounds (2j, 2u, 2t, 2w, 2s, 2r, 2x, and 2d) presented notable activity against breast cancer MDA-MB-231 cells having IC50 in the range of 11.4 ± 0.2 to 15.1 ± 0.4 µM, while the remaining fourteen compounds displayed significant to good anti-breast cancer activity. In case of α-glucosidase inhibition, eight compounds (2n, 2j, 2e, 2o, 2w, 2q, 2v, and 2l) exhibited superior inhibition against α-glucosidase enzyme with IC50 values ranging from 8.72 ± 0.14 to 16.16 ± 0.17 µM, compare with the standard acarbose. Additionally, the remaining eighteen derivatives showed significant to least inhibitory activity. The in silico docking, and molecular dynamic displayed the minimal divergence in MM-PBSA values for 2n, 2j, 2e, and 2o which suggests a strong and stable interaction with the protein's amino acid backbone. Pharmacokinetic profiles and anti-glucosidase ability suggested them as potential drug candidates for further studies.

The anti-tumor effects of cosmosiin through regulating AhR/CYP1A1-PPARγ in breast cancer.

Breast cancer is one of the threatening malignant tumors with the highest mortality and incidence rate over the world. There are a lot of breast cancer patients dying every year due to the lack of effective and safe therapeutic drugs. Therefore, it is highly necessary to develop more effective drugs to overcome breast cancer. As a glycoside derivative of apigenin, cosmosiin is characterized by low toxicity, high water solubility, and wide distribution in nature. Additionally, cosmosiin has been shown to perform anti-tumor effects in cervical cancer, hepatocellular carcinoma and melanoma. However, its pharmacological effects on breast cancer and its mechanisms are still unknown. In our study, the anti-breast cancer effect and mechanism of cosmosiin were investigated by using breast cancer models invivo and invitro. The results showed that cosmosiin inhibited the proliferation, migration, and adhesion of breast cancer cells invitro and suppressed the growth of tumor invivo through binding with AhR and inhibiting it, thus regulating the downstream CYP1A1/AMPK/mTOR and PPARγ/Wnt/β-catenin signaling pathways. Collectively, our findings have made contribution to the development of novel drugs against breast cancer by targeting AhR and provided a new direction for the research in the field of anti-breast cancer therapy.

Oleanolic acid derivative self-assembled aggregates based on heparin and chitosan for breast cancer therapy

Oleanolic acid is an active ingredient from natural products with anti-breast cancer activity. However, the poor solubility in water and low bioavailability have limited its effectiveness in clinic. To improve the anticancer activity of oleanolic acid, we synthesized a novel oleanolic quaternary ammonium (QDT), which, driven by electrostatic interactions, was introduced into heparin and coated with chitosan to obtain a QDT/heparin/chitosan nanoaggregate (QDT/HEP/CS NAs). QDT/HEP/CS NAs showed the negative zeta potential (−35.01 ± 4.38 mV), suitable mean particle size (150.45 ± 0.68 nm) with strip shape, and high drug loading (36 %). The coated chitosan had strong anti-leakage characteristics toward QDT under physiological conditions. More importantly, upon sustained release in tumor cells, QDT could significantly decrease the mitochondrial membrane potential and induce apoptosis of breast cancer cells. Further in vivo antitumor study on 4 T1 tumor-bearing mice confirmed the enhanced anticancer efficacy of QDT/HEP/CS NAs via upregulation of caspase-3, caspase-9 and cytochrome C, which was attributed to the high accumulation in tumor via the enhanced permeability and retention effect. Moreover, QDT/HEP/CS NAs significantly enhanced the biosafety and biocompatibility of QDT in vitro and in vivo. Collectively, the development of QDT/HEP/CS NAs with high antitumor activity, favorable biodistribution and good biocompatibility provided a safe, facile and promising strategy to improve the anti-cancer effect of traditional Chinese medicine ingredients.

Repositioning fluphenazine as a cuproptosis-dependent anti-breast cancer drug candidate based on TCGA database

Breast cancer is one of the most prevalent malignancies among women. Enhancing the prognosis is an effective approach to enhance the survival rate of breast cancer. Cuproptosis, a copper-dependent programmed cell death process, has been associated with patient prognosis. Inducing cuproptosis is a promising approach for therapy. However, there is currently no anti-breast cancer drug that induces cuproptosis. In this study, we repositioned the clinical drug fluphenazine as a potential agent for breast cancer treatment by inducing cuproptosis. Firstly, we utilized the Cancer Genome Atlas (TCGA) database and Connectivity Map (CMap) database to identify 22 potential compounds with anti-breast cancer activity through inducing cuproptosis. Subsequently, our findings demonstrated that fluphenazine effectively suppressed the viability of MCF-7 cells. Fluphenazine also significantly inhibited the viability of triple negative breast cancer cells MDA-MB-453 and MDA-MB-231. Furthermore, our study revealed that fluphenazine significantly down-regulated the expression of potential prognostic biomarkers associated with cuproptosis, increased copper ion levels, and reduced intracellular pyruvate accumulation. Additionally, it up-regulated the expression of FDX1 at both the mRNA and protein levels, which has been reported to play a crucial role in the induction of cuproptosis. These findings suggest that fluphenazine has the potential to be used as an anti-breast cancer drug by inducing cuproptosis. Therefore, this research provides an insight for the development of novel cuproptosis-dependent anti-cancer agents.

Physicochemical, ADMET Properties, and Molecular Docking Studies of N-benzoyl-N’-naphtylthiourea Derivatives for Anti-Breast Cancer Activity

Background: N-benzoyl-N'-naphthylthiourea (BNTU) is a thiourea-derived compound that is predicted to have anti-breast cancer activity. However, their physicochemical properties, ADMET, and receptor-specific targets for their anti-breast cancer activity have not been reported. Objective: This study aimed to predict the physicochemical properties, ADMET, and anti-breast cancer activity of BNTU and its derivatives by in silico approach. Methods: The physicochemical and ADMET properties were predicted using the pkCSM online program and ProTox-II online tool. While the anti-breast cancer activity was predicted using the molecular docking method through the Molegro Virtual Docker (MVD) program on the HER-2 receptor. The parameter observed in the molecular docking method was the bond energy value or rerank score (RS). Compounds with small RS values were predicted to have a great activity. Results: Most BNTU derivatives had lower RS values than BNTU, especially 4TBBNTU, and 4CFBNTU, although their RS values were still higher than lapatinib and TAK-285. As for the reference ligand hydroxyurea, the RS value of BNTU and its derivatives was much lower. The physicochemical and pharmacokinetic properties (ADMET) of lapatinib and TAK-285 were not better than that of BNTU and its derivatives. Conclusion: Five compounds that deserve to be synthesized and tested for anti-breast cancer activity in vitro and in vivo are 4TBBNTU, 3CFBNTU, 4CFBNTU, 4OCBNTU, and the lead compound BNTU.

Synthesis and biological evaluation of imidazolium conjugated with dimethylcardamonin (DMC) as a novel potential agent against MDA-MB-231 triple-negative breast cancer cells

A new imidazolium ionic liquid (IL) halide conjugated with dimethylcardamonin (DMC, 1), namely [Bbim]Br-DMC (3), was synthesised to improve the biological activity of the natural chalcone. DMC was isolated from seeds of Syzygium nervosum A. Cunn. ex DC. which was an effective anti-breast cancer agent. The compound 1 and 3 showed anticancer activity in MDA-MB-231 cells with IC50 values of 14.54 ± 0.99 μM and 7.40 ± 0.15 μM, respectively. MTT assay showed that compound 3 had cytotoxic effect at least two-fold greater than compound 1 but was low toxic to normal cells of Hs 578Bst. After 48 h, compound 3 at concentration of IC50 value inhibited the proliferation and induced morphological changes of MDA-MB-231 cells in a time-dependent manner. The cell cycle profile also showed that compound 3 exerted anti-proliferation activity with the cell cycle arrest at G0/G1 phase and compound 3 also induced apoptosis and reduced mitochondrial membrane potential in MDA-MB-231 cells in a dose-dependent manner. In gene expression assay, compound 3 up-regulated pro-apoptotic genes such as Bax and p53 and suppressed anti-apoptotic Bcl-2 whereas there was no effect on DNA repair gene such as PARP1. The Bax/Bcl-2 ratio was significantly increased after treated with compound 3. In the molecular docking study, the interactions between compound 3 and B-DNA structure in the minor groove region via hydrogen bonds was reported. In conclusion, [Bbim]Br-DMC or compound 3 is a potential candidate to induce apoptosis and inhibits proliferation via cell cycle arrest and decreases mitochondrial membrane of triple-negative breast cancer MDA-MB-231 cells.