UNASSIGNED: Metal nanoclusters are emerging nanomaterials applicable for drug delivery. Here, the toxicity and oxidative stress induction of divalent cationic cadmium (Cd2+) was compared with a Cd in the form of nanocluster. Then, it was used for targeted drug delivery into breast cancer cell lines.
UNASSIGNED: Using a green chemistry route, a Cd nanocluster (Cd-NC) was synthesized based on bovine serum albumin. After characterization, its genotoxicity and oxidative stress induction were studied in both in vitro and in vivo. After that, it was conjugated with hyaluronic acid (HA). The efficiency of hyaloronized-Cd-CN (HA-Cd-NC) for loading and releasing crocin (Cro), an anticancer phytochemical, was studied. Finally, it was applied for cell death induction in a panel of breast cancer cell lines.
UNASSIGNED: The comet assay results indicated that, unlike Cd2+ and potassium permanganate (KMnO4), no genotoxicity and oxidative stress was induced by Cd-NC in vitro. Then, the pharmacokinetics of this Cd-NC was studied in vivo. The data showed that Cd-NC has accumulated in the liver and excreted from the feces of mice. Unlike Cd2+, no toxicity and oxidative stress were induced by this Cd-NC in animal tissues. Then, the Cd-NC was targeted toward breast cancer cells by adding HA, a ligand for the CD44 cell surface receptor. After that, Cro was loaded on HA-Cd-NC and it was used for the treatment of a panel of human breast cancer cell lines with varying degrees of CD44. The half-maximal drug inhibitory concentration (IC50) of Cro was significantly decreased when it was loaded on HA-Cd-NC, especially in MDA-MB-468 with a higher degree of CD44 at the surface. These results indicate the higher toxicity of Cro toward breast cancers when carried out by HA-Cd-NC.
UNASSIGNED: The Cd-NC was completely safe and is a promising candidate for delivering anticancer drugs/phytochemicals into the targeted breast tumors.

Background Heliotropium bacciferum, often known as wild heliotrope or wild quailplant, is a flowering plant from the borage family. This study examines the anti-metastatic impact of H. bacciferum on Michigan Cancer Foundation-7 (MCF-7) breast cancer cells and its ability to disrupt signaling pathways. Aim To explore the anti-metastatic effect of H. bacciferum on the MCF-7 breast cancer cell line. Materials and methods For this research, MCF-7 breast cancer cells were used. Cells were cultured and subjected to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, as well as gene expression analysis for glycogen synthase kinase 3 beta (GSK3β), wingless-related integration site 2 (Wnt2), and β-catenin. The plant extract was tested to determine if it successfully blocked the signalling pathway or not.  Results The MTT test was performed to study the cytotoxic impact of H. bacciferum. At an increasing concentration of 100 μg/mL, the extract inhibited growth by 55%, whereas at 150 μg/mL, it inhibited growth by 52.5%. Maximum inhibition was seen at 150 μg/mL. H. bacciferum suppressed the GSK3β and Wnt2 signaling pathways in MCF-7 breast cancer cell lines, acting as an anti-metastatic and anticancer agent. The heliotrine compound in H. bacciferum showed high binding energy to metastatic targets such as GSK3β, Wnt2, and β-catenin. Moreover, chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties also support the study. Conclusion In this study, we can infer that H. bacciferum has a favourable anticancer impact on MCF-7 breast cancer cell lines and may be utilised as an anticancer drug against breast cancer cells. It can also be further evaluated for different breast cancers and cell lines.

Beauvericin (BEA) is a cyclic depsipeptide secondary metabolite of Fusarium species. It causes chemical hazards in food products and exists in an environment containing soil and various food types. On the other hand, the purified BEA has various biological activities and is regarded as a potential candidate for pharmaceutical research. This study was performed to assess the anti-proliferation activity of BEA against human breast cancer cells by regulating the estrogen receptor-alpha (ERα)/p38 pathway. TA and BA assays verified that BEA is a completed ER antagonist. Additionally, BEA suppressed cell proliferation in the anti-proliferation assay involving ER-positive human breast cancer cells co-treated with BPA and BEA. In respect to an anti-proliferation activity, the BPA-induced phosphorylation of p38 protein was inhibited in the presence of BEA. These results suggested that BEA exerts inhibitory potentials on endocrine disrupting effect and possibly acts as a natural therapeutic material for human estrogen hormonal health.

In this study we presented a novel series of NNO tridentate ligands generating imino, amido and oxo donor pocket for Pd(II) coordination. All the compounds were meticulously characterized by elemental analysis and advanced spectroscopic techniques, including FTIR, proton and carbon NMR. The synthesized compounds underwent rigorous evaluation for their potential as anti-cancer agents, utilizing the aggressive breast cancer cell lines MDA-MB (ATCC) and MCF-7 as a crucial model for assessing growth inhibition in cancer cells. Remarkably, the MTT assay unveiled the robust anti-cancer activity for all palladium complexes against MDA-MB-231 and MCF-7 cells. Particularly, complex [Pd(L1)(CH3CN)] exhibited exceptional potency with an IC50 value of 25.50 ± 0.30 µM (MDA-MB-231) and 20.76 ± 0.30 µM (MCF-7), compared to respective 27.00 ± 0.80 µM and 24.10 ± 0.80 µM for cisplatin, underscoring its promising therapeutic potential. Furthermore, to elucidate the mechanistic basis for the anti-cancer effects, molecular docking studies on tyrosine kinases, an integral target in cancer research, were carried out. The outcome of these investigations further substantiated the remarkable anticancer properties inherent to these innovative compounds. This research offers a compelling perspective on the development of potent anti-cancer agents rooted in the synergy between ligands and Pd(II) complexes and presenting a promising avenue for future cancer therapy endeavors.

In the current study, the squid, Sepioteuthis lessoniana ink was used as a raw material. It summarizes physicochemical, elemental, and spectral properties (UV/Visible spectroscopy and FT-IR) of crude ink, whereas the biochemical analysis was performed with crude ink (CI) as well as melanin-free ink (MFI). The percentage yield was analyzed using various solvent extracts of CI and MFI. GC-MS was performed for the chemical constituents of the methanolic extract of ink. Furthermore, the methanolic extract was subjected to various biological applications. The physicochemical analysis defines the presence of moisture, ash, extractive value, solubility, and thermal stability of CI. The biochemical analysis reveals protein, lipid, and carbohydrate of 2.5, 2.2, and 2.37 mg/ml for CI and 2.8, 3.7, and 4.51 mg/ml for MFI respectively. The extract showed the highest zone of inhibition at 100 μg/ml. The antioxidant activity reveals the highest percentage of radical-scavenging activity in nitric oxide (NO) (89%), and total antioxidant capacity (TAC) assay showed the highest inhibition activity of 0.41 nm at 100 µg/ml. The cytotoxic ability of methanolic extract against MDA-MB-231 breast cancer cell line revealed an IC50 value of 10.13 μg/ml. Toxicity assay showed increased mortality of Artemia nauplii at higher concentrations (1000 ppm/40%) of extract. These findings indicate that S. lessoniana ink is a novel prospective product that needs to be characterized in order to increase its pharmacological activity.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s13205-023-03830-6.

Glutathione transferase Pi (GSTP1) expression is increased in many cancer types and is associated with multidrug resistance and apoptosis inhibition. Inhibitors of GSTP1-1 have the potential to overcome drug resistance and improve chemotherapy efficacy as adjuvant agents. This study investigated the effects of catechin and gossypol on human glutathione transferase Pi (GSTP1-1) activity and their cytotoxic effects on breast cancer cells (MCF-7) individually and in combination with tamoxifen (TAM). Gossypol effectively inhibited the enzyme with an IC50 value of 40 μM, compared to 200 μM for catechin. Gossypol showed stronger inhibition of GSTP1-1 activity (Ki = 63.3 ± 17.5 μM) compared to catechin (Ki = 220 ± 44 μM). Molecular docking analysis revealed their binding conformations to GSTP1-1, with gossypol binding at the subunit interface in an un-competitive manner and catechin showing mixed non-competitive inhibition. Gossypol had severe cytotoxic effects on both MCF-7 cells and normal BJ1 cells, while catechin had a weak cytotoxic effect on MCF-7 cells only. Combination therapy with TAM resulted in cytotoxicity of 27.3% and 35.2% when combined with catechin and gossypol, respectively. Gossypol showed higher toxicity to MCF-7 cells, but its strong effects on normal cells raised concerns about selectivity and potential side effects.

UNASSIGNED: The present study evaluated the protein-based analysis to unravel the role and mechanism behind the Dendropthae falcata plant extract treatment in breast cancer cells.
UNASSIGNED: The protein sample was extracted from the cancer cells after treatment with the plant extract and subjected to two-dimensional electrophoresis for protein separation. Further, the proteins that were differentially regulated among the samples which were treated and non-treated were selected and processed further for protein identification using a tandem mass spectrometry approach.
UNASSIGNED: Using these strategies, we identified 16 potential candidates which were showing remarkable changes in treated samples. All the candidates were analyzed further for gene ontology analysis, and it was observed that all proteins were involved in multiple pathways pertaining to the carcinogenesis process. Specifically, apoptotic pathway proteins including BAD, BIK, BID, CASP8, MCL1, BCL2, and BAK1 were highly impacted by treatment with D. falcata plant extract. All these protein hits were further taken for validation experiments using RT PCR analysis.
UNASSIGNED: Initiation of these apoptotic proteins by D. falcata plant extract treatment in breast cancer cells shows a positive direction toward nature-based alternative medicine.

BACKGROUND: Breast cancer is the most fatal type of cancer in women worldwide. Many chemotherapeutics targeted breast cancer however, they have frightening side effects. One method of controlling cancer cell growth is targeting apoptosis.
OBJECTIVE: This study aimed to induce apoptosis in breast cancer cells by purifying L-asparaginase from human breast milk Lactobacillus reuteri isolates via inhibition of Caspases 8 and 9.
METHODS: The best L. reuteri isolates producing L-asparagine with the highest enzyme activity were identified from human breast milk and chosen for L-asparaginase purification. The MTT cell viability assay used for measure the toxicity of the enzyme. Breast cancer cell line was used to study the effect of the enzyme on the caspase 8 and caspase 9 gene expression.
RESULTS: The MTT cell viability assay showed the inhibition rates ranged between 30% and 80%, of cell death, occurred when 3.125, 6.25, 12.5, 25, 50, and 100 μg/ml of the enzyme used and IC50 was 4.305 μg/ml. The breast cell lines were treated with the enzyme at a concentration of IC50 value. The Cas8 and Cas9 genes expression in L-asparagine treated breast cancer cell line at a concentration of IC50 value were upregulated (the fold of gene expression are 2.071 and 1.197 respectively).
CONCLUSIONS: Breast milk L. reuteri L-asparaginase induces apoptosis via Cas8 and Cas9 upregulation in the breast cancer cell line. L. reuteri L-asparaginase treatment may be the hopeful approach for the management of breast cancer. Furthermore, the results may highlight the fact that the presence of L-asparaginase-producing L. reuteri isolates in human breast milk may aid in breast cancer improvement or even prevention.

Obstacles to the successful treatment of breast cancer patients with chemotherapeutic agents can be overcome with effective new strategies. It is still unclear how folic acid affects the onset and spread of breast cancer. The purpose of this study was to determine how folic acid affected the apoptotic and autophagic pathways of the breast cancer cell lines MCF-7 and MDA-MB-231. In the present study, folic acid was applied to MCF-7 and MDA-MB-231 breast cancer cell lines at different concentrations and for different durations. MTT analysis was used to investigate cytotoxic activity. All groups underwent the Tunel staining procedure to identify apoptosis and the immunofluorescence staining approach to identify the autophagic pathway. 24-hour folic acid values were accepted as the most appropriate cytotoxic dose. In MCF-7, cell cycle arrest was observed in the S phase and MDA-MB-231 G1/G0 phases. When apoptotic TUNEL staining was evaluated in both cell lines, folic acid significantly increased apoptosis. While a significant difference was observed between the groups in terms of Beclin 1 immunoreactivity in the MDA-MB-231 cell line, there was no significant difference in the MCF-7 cell line. In addition, statistical significance was not observed LC3 immunoreactivity in both cell lines. In the study, it was observed that folic acid induced autophagy at the initial stage in the MDA-MB-231 cell line but had no inductive effect in the MCF-7 cell line. In conclusion, our findings showed that folic acid has a potential cytotoxic and therapeutic effect on MCF-7 and MDA-MB-231 breast cancer cell lines.

BACKGROUND: Hydrogel nanoparticles, also known as nanogels (NGs), have been recently proposed as alternative supramolecular vehicles for the delivery of biologically relevant molecules like anticancer drugs and contrast agents. The inner compartment of peptide based NGs can be opportunely modified according to the chemical features of the cargo, thus improving its loading and release. A full understanding of the intracellular mechanism involved in nanogel uptake by cancer cells and tissues would further contribute to the potential diagnostic and clinical applications of these nanocarriers, allowing the fine tuning of their selectivity, potency, and activity. The structural characterization of nanogels were assessed by Dynamic Light Scattering (DLS) and Nanoparticles Tracking Analysis (NTA) analysis. Cells viability of Fmoc-FF nanogels was evaluated by MTT assay on six breast cancer cell lines at different incubation times (24, 48, and 72 h) and peptide concentrations (in the range 6.25 × 10-4 ÷ 5·10-3 × wt%). The cell cycle and mechanisms involved in Fmoc-FF nanogels intracellular uptake were evaluated using flow cytometry and confocal analysis, respectively. Fmoc-FF nanogels, endowed with a diameter of ~130 nm and a zeta potential of ~-20.0/-25.0 mV, enter cancer cells via caveolae, mostly those responsible for albumin uptake. The specificity of the machinery used by Fmoc-FF nanogels confers a selectivity toward cancer cell lines overexpressing the protein caveolin1 and efficiently performing caveolae-mediated endocytosis.