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Antigenotoxic, antiproliferative and antimetastatic properties of a combination of native medicinal plants from Argentina.

ETHNOPHARMACOLOGICAL RELEVANCE: Jarilla is the common name of an appreciated group of native plants from the semi-arid region in Argentina (Larrea cuneifolia Cav., Larrea divaricata Cav. and Zuccagnia punctata Cav.) that have been historically consumed to heal respiratory, musculoskeletal and skin ailments, as well as recommended for weakness/tiredness, hypertension, diabetes and cancer treatment. It was previously reported that some biological properties could be improved when these plants are used jointly. Infusions of a defined mixture, composed by three Jarilla species, L. cuneifolia: L. d

The role of glycocalyx-protein corona interactions in the cell type-specific uptake of mRNA nanocarriers.

Non-viral nanocarriers for oligonucleotide delivery have enormous therapeutic potential, but the factors determining cell type-specific uptake remain incompletely understood. One major cell surface component that delivery vectors encounter is the glycocalyx. While membrane glycans are established interactors for many viruses, their impact on non-viral particles has remained underexplored. Here, we show that the role of membrane glycosaminoglycans (GAGs) in mRNA delivery differs across nanocarrier categories and cell types. We employed novel glycosylation inhibitors as well as enzymatic strateg

VALD-3 Induces GSDME-Dependent Pyroptosis via ROS/JNK/Bax Pathway in Triple-Negative Breast Cancer Cells.

Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, known for its high malignancy, elevated risk of recurrence and metastasis, and limited therapeutic options, resulting in the poorest prognosis among breast cancer types. This study explores the anticancer effects of VALD-3, a Schiff base ligand derivative, on breast cancer cells. While VALD-3 exhibited cytotoxic effects on both triple-negative breast cancer (TNBC) and estrogen receptor-positive (ER+) MCF-7 cells, it more potently inhibited TNBC cell viability. More importantly, VALD-3 induced characteri…

Overcoming ABCB1-mediated multidrug resistance by transcription factor BHLHE40.

Multidrug resistance (MDR) hinders treatment efficacy in cancer therapy. One typical mechanism contributing to MDR is the overexpression of permeability-glycoprotein (P-gp) encoded by ATP-binding cassette subfamily B member 1 (ABCB1). Basic helix-loop-helix family member e40 (BHLHE40) is a well-known transcription factor that has pleiotropic effects including the regulation of cancer-related processes. However, whether BHLHE40 regulates MDR is still unknown. Chromatin immunoprecipitation-seq study revealed BHLHE40 occupancy in the promoter of ABCB1 gene. Adriamycin (ADM)-resistant human chroni

Synthesis and Anticancer Activity of Novel Dual Inhibitors of Human Protein Kinases CK2 and PIM-1.

CK2 and PIM-1 are serine/threonine kinases involved in the regulation of many essential processes, such as proliferation, differentiation, and apoptosis. Inhibition of CK2 and PIM-1 kinase activity has been shown to significantly reduce the viability of cancer cells by inducing apoptosis. A series of novel amino alcohol derivatives of parental DMAT were designed and synthesized as potent dual CK2/PIM-1 inhibitors. Concomitantly with the inhibition studies toward recombinant CK2 and PIM-1, the influence of the obtained compounds on the viability of three human carcinoma cell lines, i.e., acute

Enhancing Tamoxifen Therapy with α-Mangostin: Synergistic Antiproliferative Effects on Breast Cancer Cells and Potential Reduced Endometrial Impact.

Breast cancer is the most prevalent neoplasia among women worldwide. For the estrogen receptor-positive (ER+) phenotype, tamoxifen is the standard hormonal therapy; however, it carries the risk of promoting endometrial carcinoma. Hence, we aimed to evaluate the antiproliferative effect of the phytochemical α-mangostin (AM) as a co-adjuvant alongside tamoxifen on breast cancer cells to improve its efficacy while reducing its adverse effects on endometrium. For this, ER+ breast cancer cells (MCF-7 and T-47D) and endometrial cells (N30) were treated with AM, 4-hydroxytamoxifen (4-OH-TMX), and the

Antiproliferative activity of Vallaris glabra Kuntze (Apocynaceae).

BACKGROUND: Our earlier study on the antiproliferative (APF) activity of leaf extracts of ten Apocynaceae species showed that leaves of Vallaris glabra possessed strong and broad-spectrum properties. MATERIALS AND METHODS: In this study, sequential extracts of leaves, flowers and stems, and fractions and isolated compounds from dichloromethane (DCM) leaf extract of V. glabra were assessed for APF activity using the sulphorhodamine B (SRB) assay. Apoptotic effect of MDA-MB-231 cancer cells treated with DCM leaf extract of V. glabra was studied using Hoechst 33342 dye and caspase colorimetry.

Targeting dysregulated molecular pathways in cancer cell lines using small molecule inhibitors as a promising therapeutic strategy.

Biologically active heterocycles hold considerable potential in modulating cellular pathways associated with cancer progression. The present study focuses on the design and synthesis of novel thiadiazole-thiazolidinone hybrid scaffolds aimed at inhibiting the proliferation of cancer cells. The synthesized compounds were evaluated for their cytotoxic efficacy against human cancer cell lines, including HepG2 (hepatocellular carcinoma), MCF-7 (breast adenocarcinoma), HCT-116 (colorectal carcinoma), and W138 (lung fibroblast-derived carcinoma). Doxorubicin was used as a reference standard. Among t

An enzyme-mediated controlled release system for curcumin based on cyclodextrin/cyclodextrin degrading enzyme.

In this study, an enzyme-triggered system based on β-cyclodextrin (β-CD) has been developed to achieve controlled release of hydrophobic drugs in the presence of maltogenic amylase (MAase). The inclusion complex formation of curcumin (CUR), as a model anticancer compound, with β-CD was characterized by fluorescence and Fourier transform infrared (FTIR) spectroscopy. CUR was loaded into β-CD with an encapsulation efficiency of approximately 30 %. The in vitro profiles of CUR release from β-CD showed that 100 % of the drug was released after one hour incubation in the presence of MAase with cycl

Structure-based identification of a non-covalent thioredoxin reductase inhibitor with proven ADMET suitability.

Thioredoxin reductase 1 (TrxR1), a selenoprotein enzyme crucial for redox homeostasis in mammals, has emerged as a promising target for anticancer therapy. In this study, we present a non-covalent TrxR1 inhibitor, identified through an integrated experimental and computational approach. After identifying a plausible druggable cavity, a molecular docking-based virtual screening of over 90,000 lead-like compounds was performed. The selected compounds were evaluated for their impact on TrxR1 activity, leading to the identification of the most promising candidate, C55. The identified compound, alr

Design and synthesis of kidjoranin neoglycoside derivatives as potent anticancer agents.

Kidjoranin (1), one of the major C21-steroidal aglycones isolated from Cynanchum otophyllum in our previous work, was used as the substrate for the preparation of a series of 3β-O-neoglycoside derivatives via the CdCO3-mediated Koenigs-Knorr reaction. The resulting compounds were evaluated for cytotoxicity against a panel of human cancer cell lines (MCF-7, HCT-116, HeLa, and HepG2). Among them, compounds 2b, 2l, and 4a displayed significant cytotoxic effects, with IC50 values ranging from 6.00 to 9.41 μM, 2.58 to 3.20 μM, and 3.02 to 4.48 μM, respectively. Preliminary mechanistic studies revea

Organotin(IV) carboxylates-derivatives of bexarotene: synthesis, characterization, anti/prooxidant activity, and high cytotoxicity.

New organotin(IV) mono- and bis-carboxylate complexes derivatives of Bexarotene (bex), viz. R3Sn(bex) (where R = Ph (1); Cy (2); nBu (3)), and R2Sn(bex)2 (where R = Et (4), tBu (5), Ph (6)) were synthesized. Compounds were fully characterized using spectroscopic techniques. The molecular structure for the Ph3Sn(bex) (1) in crystalline form was established by single-crystal X-ray diffraction. Electrochemical properties of tin complexes and bexarotene were investigated by cyclic voltammetry. The target compounds are characterized by the high oxidation potentials in the mixture of aprotic solvent

In vitro synergistic cytoreductive effects of zoledronic acid and radiation on breast cancer cells.

IntroductionBisphosphonates are mostly used in the treatment of bone metastases. They have been shown to act synergistically with other chemotherapeutic agents. It is not known, however, whether similar synergistic effects exist with radiation on breast cancer cells.MethodsHuman MCF-7 breast cancer cells were treated with up to 100 microM zoledronic acid, were irradiated with up to 800 cGy or were exposed to combinations of both treatments to determine the antiproliferative effects of zoledronic acid and radiation.ResultsZoledronic acid and radiation caused a dose-dependent and time-dependent

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… -7 cell viability. … Figure 2 Radiation dose effect on MCF-7 cells. (a) MCF 7 cells treated with radiation alone. (b) The cytotoxic effect of radiation on MCF-7 cells increased steadily after incubating the cells with higher zoledronic acid concentrations. Ctl, control. …

Suramin-induced growth inhibition and insulin-like growth factor-I binding blockade in human breast carcinoma cell lines: potentially related events.

Suramin, a polyanionic drug used in the treatment of trypanosomiasis and onchocerciasis, inhibits growth factor-induced mitogenesis in several human tumours. We have investigated the effect of suramin on human breast cancer cell lines (HBCCL). By cell counts and thymidine incorporation we found that 50 to 400 micrograms/ml suramin inhibits the proliferation of HBCCL in a dose-dependent and reversible fashion (ID50 approximately 200 micrograms/ml for MCF-7 and MDA-MB 231). Radioreceptor and affinity cross-linking assays showed that suramin was also able to reduce the binding of insulin-like gro

Essential oil composition, in vitro antidiabetic, cytotoxicity, antimicrobial, antioxidant activity, and in silico molecular modeling analysis of secondary metabolites from Justicia schimperiana.

Justicia schimperiana, known as "Dhumuugaa" in Afan Oromo and "Sensel" or "Smiza" in Amharic, is traditionally used to treat ailments such as scabies, fever, asthma, diarrhea, malaria, and more. This study explored the chemical composition and biological activity of its extracts and isolated compounds. The essential oils were extracted using the hydrodistillation method, and their chemical composition was evaluated using GC-MS. GC-MS analysis identified 54 and 52 chemical components in the essential oils (EOs) from roots and leaves, respectively. The structures of the isolated compounds have b

Synthesis and characterization of Schiff base containing bovine serum albumin-gum arabic aldehyde hybrid nanogels via inverse miniemulsion for delivery of anticancer drug.

The periodate modified gum arabic was used as a natural-based, non-toxic cross-linker to synthesize hybrid bovine serum albumin-gum arabic a … assay revealed the in vitro hemocompatibility of the hybrid nanogels which inhibited the growth of MCF-7 cells with an IC50 value of 16.21 μM. The present study suggested that these biobased hybrid nanogels could have a great potential in drug delivery and other biomedical applications.

Augment of Oxidative Damage with Enhanced Photodynamic Process and MTH1 Inhibition for Tumor Therapy.

Tumor cells adapt to reactive oxygen species (ROS) attacking by launching DNA damage repairing mechanisms such as nucleotide pool sanitizing enzyme mutt homologue 1 (MTH1) to mitigate the oxidatively induced DNA lesions, which could greatly limit the therapeutic efficiency of current oxidation therapy. Here, an amplified oxidative damage strategy for tumor therapy was proposed that was focused not only on the enhancement of ROS generation but also the inhibition of subsequent MTH1 enzyme activity simultaneously. In our formulation, mesoporous silica-coated Prussian blue nanoplatforms (PB@MSN)

Amino acid response by Halofuginone in Cancer cells triggers autophagy through proteasome degradation of mTOR.

BACKGROUND: In the event of amino acid starvation, the cell activates two main protective pathways: Amino Acid starvation Response (AAR), to … pes of human cancer cells (thyroid cancer WRO cells, ovarian cancer OAW-42 cells, and breast cancer MCF-7 cells), HF induced both the AAR and the autophagy pathways time-dependently. In WRO cells, which showed the strongest induction of autophagy and of AAR, global protein synthesis was little if any affected. Consistently, 4E-BP1 and (rp)S6 were phosphorylat …

A Network Pharmacology-Based Analysis of Multi-Target, Multi-Pathway, Multi-Compound Treatment for Ovarian Serous Cystadenocarcinoma.

BACKGROUND AND OBJECTIVES: Pharmacological control against ovarian serous cystadenocarcinoma has received increasing attention. The purpose of this study was to investigate multi-drug treatments as synergetic therapy for ovarian serous cystadenocarcinoma and to explore their mechanisms of action by the network pharmacology method. METHODS: Genes acting on ovarian serous cystadenocarcinoma were first collected from GEPIA and DisGeNET. Gene Ontology annotation, Kyoto Encyclopedia of Genes and Genomes pathway, Reactome pathway, and Disease Ontology analyses were then conducted. A connectivity ma

An anionic phthalocyanine decreases NRAS expression by breaking down its RNA G-quadruplex.

Aberrant activation of RAS signalling pathways contributes to aggressive phenotypes of cancer cells. The RAS-targeted therapies for cancer, therefore, have been recognised to be effective; however, current developments on targeting RAS have not advanced due to structural features of the RAS protein. Here, we show that expression of NRAS, a major isoform of RAS, can be controlled by photo-irradiation with an anionic phthalocyanine, ZnAPC, targeting NRAS mRNA. In vitro experiments reveal that ZnAPC binds to a G-quadruplex-forming oligonucleotide derived from the 5'-untranslated region of NRAS mR