Evaluation of Induced Apoptosis by Biosynthesized Zinc Oxide Nanoparticles in MCF-7 Breast Cancer Cells Using Bak1 and Bclx Expression.

Zinc oxide nanoparticles (ZnO NPs) have peaked interests in many researches in these recent years due to their advantageous application in modern health care applications. Therefore, we successfully synthesized ZnO NPs by Acacia luciana flower extract as stabilizing, reducing and capping agent, to investigate the antiproliferative potential and apoptosis induction in breast cancer cell lines. The involvements of Acacia luciana bioactive compounds in the stabilization of the ZnO NPs were confirmed by FTIR analysis. FESEM and EDS instruments confirmed that biosynthesized nanoparticles have an irregular morphology and mostly composed of Zn, C, and O respectively. The TEM and zeta potential instruments confirmed that biosynthesized nanoparticles have slight negative charges with particle size of 40 nm. The survivorship of MCF-7 cells were examined by MTT assay and revealed that ZnO NPs inhibited cell viability in a dose- and time-dependent effect with IC50 value of 3.1 µg/mL after 72 h exposure. Also, as a novel work onto ZnO NPs obtained by Acacia extracts, the Bak1/Bclx expression ratio was elucidated utilizing RT-PCR technique. The results demonstrated that ZnO NPs could enhance the expression ratio; therefore they have the potential to induce apoptosis in breast cancer cells via mitochondria-mediated apoptotic pathway.

Multifunctional mitoxantrone-conjugated magnetic nanosystem for targeted therapy of folate receptor-overexpressing malignant cells.

BACKGROUND: Targeted delivery of anticancer chemotherapeutics such as mitoxantrone (MTX) can significantly intensify their cytotoxic effects selectively in solid tumors such as breast cancer. In the current study, folic acid (FA)-armed and MTX-conjugated magnetic nanoparticles (MNPs) were engineered for targeted eradication of folate receptor (FR)-positive cancerous cells. Polyethylene glycol (PEG), FA and MTX were covalently conjugated onto the MNPs to engineer the PEGylated FA-MTX-MNPs. The internalization studies were performed using fluorescein isothiocyanate (FITC)-labeled FA-decorated MNPs (FA-FITC-MNPs) in both FR-positive MCF-7 cells and FR-negative A549 cells by means of fluorescence microscopy and flow cytometry. The cellular and molecular impacts of FA-MTX-MNPs were examined using trypan blue cell viability and FITC-labeled annexin V apoptosis assays and 4',6-diamidino-2-phenylindole (DAPI) staining, DNA ladder and quantitative polymerase chain reaction (qPCR) assays. RESULTS: The FR-positive MCF-7 cells showed significant internalization of the FA-FITC-MNPs, but not the FR-negative A549 cells. The FR-positive cells treated with the PEGylated FA-MTX-MNPs exhibited the IC50 values of 3 µg/mL and 1.7 µg/mL, 24 h and 48 h post-treatment, respectively. DAPI staining and DNA ladder assays revealed significant condensation of nucleus and fragmentation of genomic DNA in the FR-positive MCF-7 cells treated with the PEGylated FA-MTX-MNPs as compared to the FR-negative A549 cells. The FITC-labeled annexin V assay confirmed emergence of late apoptosis (>80%) in the FR-positive MCF-7 cells treated with the PEGylated FA-MTX-MNPs, but not in the FR-negative A549 cells. The qPCR analysis confirmed profound cytotoxic impacts via alterations of apoptosis-related genes induced by MTX-FA-MNPs in MCF-7 cells, but not in the A549 cells. CONCLUSION: Our findings evince that the engineered PEGylated FA-MTX-MNPs can be specifically taken up by the FR-positive malignant cells and effectively demolish them through up-regulation of Bcl-2-associated X protein (Bax) and Caspase 9 and down-regulation of AKt. Hence, the engineered nanosystem is proposed for simultaneous targeted imaging and therapy of various cancers overexpressing FRs.

Corrigendum to: Investigation of the Apoptosis Inducing and ß-catenin Silencing by Tetradentate Schiff Base Zinc(II) Complex on the T-47D Breast Cancer Cells.

A typographical error appeared in the author affiliation titled "Investigation of the Apoptosis Inducing and ß-catenin Silencing by Tetradentate Schiff Base Zinc(II) Complex on the T-47D Breast Cancer Cells", published in Anti-Cancer Agents in Medicinal Chemistry, 2023, 23(15) [1]. Details of the error and a correction are provided here. Original: Author Affiliation: 2Department of Breast Medicine, Cancer Hospital Chinese Academy of Medical Science, Liaoning Provincial Cancer Hospital, Shenyang, Liaoning, 110042, China Corrected: Author Affiliation: 2Department of Breast Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China We regret the error and apologize to readers. The original article can be found online at https://www.eurekaselect.com/article/131718.

Investigation of the Apoptosis Inducing and ß-catenin Silencing by Tetradentate Schiff Base Zinc(II) Complex on the T-47D Breast Cancer Cells.

INTRODUCTION: Several mechanisms are known for the anticancer effects of cisplatin. However, its most wellknown function involves binding to DNA and activating the DNA damage response. METHODS: Despite its good effects, the treatment process often leads to chemoresistance and affects the mechanisms that support cell survival, such as pathways that promote cell growth, apoptosis, DNA damage repair, and endocytosis. For this reason, we investigated the effects of a new metal complex (tetradentate Schiff base zinc(II) complex) on breast cancer cells (T-47D). We evaluated its effect on cytotoxicity, apoptosis, and drug resistance in comparison to cisplatin. RESULTS: The results of the MTT test showed that tetradentate Schiff base zinc(II) complex has good cytotoxicity compared to cisplatin. The IC50 values for the [Zn(SB)]Cl2 complex and cisplatin after 72 h of exposure were equal to 42.1 and 276.1 µM, respectively. Real-time PCR assay confirmed that the [Zn(SB)]Cl2 complex activated the mitochondrial pathway of apoptosis and increased the expression of Bak1 and caspase-3 genes significantly compared to cisplatin. More importantly, the [Zn(SB)]Cl2 was able to reduce the expression of the ß-catenin gene, which plays a role in drug resistance, by 0.011 compared to the control. CONCLUSION: Therefore, we can hope for this new complex because, without the help of any ß-catenin silencing agent, it was able to inhibit the drug resistance in the T-47D cell line that overexpresses the ß-catenin gene.

Hyaluronan magnetic nanoparticle for mitoxantrone delivery toward CD44-positive cancer cells.

Hyaluronic acid (HA) is increasingly investigated for biomedical applications such as regenerative medicine, aesthetic medicine, and drug delivery. Accordingly, conjugation of HA to PEGylated MNPs could increase the active targeting ability of nano-drug carriers toward CD44 receptors and be useful in a clinical setting such as drug delivery. So, we chemically conjugated mitoxantrone (MTX) to HA-PEGylated MNPs to use concurrent advantages such as prolong the circulation time, decrease the side effects and delivery toward special tumor cells. Size of the Fe3O4-DPA-PEG-HA-MTX NPs was determined ∼200 nm utilizing FESEM and DLS. Stability analysis confirmed that prepared MNPs were stable in physiological conditions even after 8 days and only 47.3% of MTX was liberated from nanocarriers, in the event that, acidic condition and also presence of protease enzyme accelerated the amount of MTX release to 100% after 8 days of incubation. The in vitro cytotoxicity analysis by MTT assay revealed that viable cell numbers were reduced by 32% when MTX-HA-MNPs were applied against MDA-MB-231 cell lines, while they showed significant decreased cellular cytotoxic effects on cell viability in the MCF-7 cell lines which express lower levels of CD44 receptor at the cell surface. Also, results of flow cytometry analysis following 24 h exposure confirmed that MTX-HA-MNPs have significant induction of apoptosis in MDA-MB-231 cell lines (70.3%) which contains high levels of CD44 expression, whereas there was little effect on the induction of apoptosis in MCF-7 cell lines (5%). The obtained binding models through molecular docking simulation related to each single moieties of prepared MNPs clearly confirmed that MTX-HA-MNPs can easily be bonded to the CD44 receptor with more affinity value in comparison to HA ligand, and so conjugation of HA to MNPs can be a good way for MTX delivery toward special tumor cells or tissues.

Exploring isoxsuprine hydrochloride binding with human serum albumin in the presence of folic acid and ascorbic acid using multispectroscopic and molecular modeling methods.

Isoxsuprine hydrochloride (vasodilator drug), folic acid and ascorbic acid are medicines which can be utilized alone or simultaneously by pregnant women. In the present work the competitive binding of isoxsuprine hydrochloride (ISO) with human serum albumin (HSA) in the absence and presence of folic acid (FOL) and ascorbic acid (AS) was investigated using different spectroscopic probes and molecular docking studies. The results of fluorescence suggested that isoxsuprine alone or in the presence of ascorbic acid can bind to HSA and quench the fluorescence of HSA with static mechanism but For HSA-folic acid-isoxsuprine system, dynamic type of quenching mechanisms is involved. The values of binding constants (KHSA-ISO~1.2×103M-1, KHSA-AS-ISO~2.1×103M-1and KHSA-FOL-ISO~0.7×103M-1) suggested that affinity of HSA to isoxsuprine increased in the presence of ascorbic acid while the presence of folic acid reduced the affinity of protein to isoxsuprine. The results of FT-IR and circular dichroism measurements indicated that the binding of isoxsuprine to HSA in the absence and the presence of folic acid and ascorbic acid may induce conformational and microenvironmental changes of protein. Not only do these types of spectroscopy techniques provide all the information about the systems, molecular docking, also emphasizes the results and is employed for the identification of the active site residues, bioactive conformer of Isoxsuprine and their critical interactions.

Comparative study on the anticancer activities and binding properties of a hetero metal binuclear complex [Co(dipic)2Ni(OH2)5]·2H2O (dipic=dipicolinate) with two carrier proteins.

Recognizing of binding mechanisms between drugs and carrier proteins is basic for us to understand the pharmacokinetics and pharmacodynamics of them. In this research, the anticancer activities of a binuclear complex [Co(dipic)2Ni(OH2)5]·2H2O (dipic=dipicolinate) against MDA-MB-231 cell lines were studied. Results of MTT assay and flow cytometry analysis revealed that above complex can induce the cytotoxicity and the apoptosis in breast cancer cell lines. So, this complex was selected to investigate its binding to human serum albumin (HSA) and bovine ß-lactoglobulin (ßLG) by spectroscopic methods (UV-visible, fluorescence and FT-IR) along with molecular docking technique. The fluorescence data showed Co-Ni complex quench the fluorescence of both proteins by a static quenching mechanism and HSA has stronger binding affinity toward Co-Ni complex than ßLG. The binding constant (Kb), number of binding sites (n) and thermodynamic parameters were calculated and showed that the Co-Ni complex binds to protein (HSA and ßLG) through hydrogen bonding and van der Waals forces with one binding site. The results of UV-visible measurements indicated that the binding of above complex to HSA and ßLG may induce conformational and micro-environmental changes of studied proteins. Protein-ligand docking analysis confirmed that the Co-Ni complex binds to residues located in the subdomain IIA of HSA and site II of ßLG.