A role for RIO kinases in the crosshair of cancer research and therapy.

RIO (right open reading frame) family of kinases including RIOK1, RIOK2 and RIOK3 are known for their role in the ribosomal biogenesis. Dysfunction of RIO kinases have been implicated in malignancies, including acute myeloid leukemia, glioma, breast, colorectal, lung and prostatic adenocarcinoma suggesting RIO kinases as potential targets in cancer. In vitro, in vivo and clinical studies have demonstrated that RIO kinases are overexpressed in various types of cancers suggesting important roles in tumorigenesis, especially in metastasis.

An Immunoinformatic Strategy to Develop New Multi-epitope Vaccine.

causes a life-threatening disease known as tuberculosis (TB). In 2021, tuberculosis was the second cause of death after COVID-19 among infectious diseases. Latent life cycle and development of multidrug resistance in one hand and lack of an effective vaccine in another hand have made TB a global health issue.

Quercetin ameliorates Di (2-ethylhexyl) phthalate-induced nephrotoxicity by inhibiting NF-κB signaling pathway.

This study aimed to evaluate the possible protective effects of quercetin, a natural flavonoid, against nephrotoxicity induced by Di (2-ethylhexyl) phthalate (DEHP) in kidney tissue of rats and human embryonic kidney (HEK) 293 cell line. The HEK-293 cells were treated with different concentrations of quercetin 24 h before treatment with monoethylhexyl phthalate (MEHP). Male rats were treated with 200-mg/kg DEHP, 200-mg/kg DEHP plus quercetin (50 and 100 mg/kg), and 200-mg/kg DEHP plus vitamin E (20 mg/kg) for 45 days by gavage.

Comparative proteomics study of proteins involved in induction of higher rates of cell death in mitoxantrone-resistant breast cancer cells MCF-7/MX exposed to TNF-α.

Objectives: Resistance to medications is one of the main complications in chemotherapy of cancer. It has been shown that some multidrug resistant cancer cells indicate more sensitivity against cytotoxic effects of TNF-α compared to their parental cells. Our previous findings indicated vulnerability of the mitoxantrone-resistant breast cancer cells MCF-7/MX to cell death induced by TNF-α compared to the parent cells MCF-7.

The implication of mitochondrial dysfunction and mitochondrial oxidative damage in di (2-ethylhexyl) phthalate induced nephrotoxicity in both and models.

Di-(2-ethylhexyl) phthalate (DEHP) and its main metabolite, monoethylhexyl phthalic acid (MEHP), are a serious threat to human and animals' health in the current century. However, their exact mechanism to induce nephrotoxicity is not clear. In the current study, we addressed toxic effects of MEHP and DEHP on embryonic human kidney cells (HEK-293 cell line) and kidney tissue of rats, respectively.

Colchicine-like β-acetamidoketones as inhibitors of microtubule polymerization: Design, synthesis and biological evaluation of anticancer activity.

Objectives: In this study a series of novel colchicine-like β-acetamidoketones was designed and synthesized as potential tubulin inhibitors.

Materials And Methods: The cytotoxicity of the novel synthesized β-acetamidoketones was assessed against two cancerous cell lines including MCF-7 (human breast cancer cells) and A549 (adenocarcinomic human alveolar basal epithelial cells) employing the MTT test. Tubulin polymerization test was done by using a commercial kit (tubulin polymerization assay kit).

Wnt-β-catenin Signaling Pathway, the Achilles' Heels of Cancer Multidrug Resistance.

Background: Most of the anticancer chemotherapies are hampered via the development of multidrug resistance (MDR), which is the resistance of tumor cells against cytotoxic effects of multiple chemotherapeutic agents. Overexpression and/or over-activation of ATP-dependent drug efflux transporters is a key mechanism underlying MDR development. Moreover, enhancement of drug metabolism, changes in drug targets and aberrant activation of the main signaling pathways, including Wnt, Akt and NF-κB are also responsible for MDR.

TNF-α exerts cytotoxic effects on multidrug resistant breast cancer MCF-7/MX cells via a non-apoptotic death pathway.

Tumor necrosis factor-α (TNF-α) is a cytokine involved in the various physiopathological processes such as autoimmune disorders and inflammation related diseases. Some multidrug resistant (MDR) cancer cell lines including MCF-7/MX are more vulnerable to cytotoxic effects of TNF-α than their parental lines. In this study, breast cancer cell line MCF-7 and its MDR derivative MCF-7/MX were exposed to TNF-α afterward various downstream signaling mediators of TNF-α were analyzed.

evaluation of dihydropyridine-3-carbonitriles as potential cytotoxic agents through PIM-1 protein kinase inhibition.

PIM-1 protein kinase inhibitor belongs to a novel class of serine/threonine kinases. As PIM-1 is overexpressed in cancer cells and possesses oncogenic functions, its inhibition provides a new option in cancer therapy. In this study, inhibitory effects of seven analogues of 1, 2-dihydropyridine-3-carbonitrile derivatives , on the activity of recombinant PIM-1 were evaluated using dimethylthiazol diphenyltetrazolium bromide (MTT) assay.

Inhibition of Akt phosphorylation attenuates resistance to TNF-α cytotoxic effects in MCF-7 cells, but not in their doxorubicin resistant derivatives.

Objectives: Acquisition of TNF-α resistance plays role in the onset and growth of malignant tumors. Previous studies have demonstrated that MCF-7 cell line and its doxorubicin resistant variant MCF-7/Adr are resistant against the cytotoxic effects of TNF-α. In this study, we investigated the role of Akt activation in resistance of MCF-7 and MCF-7/Adr against TNF-α cytotoxicity.

Curcumin: An Effective Inhibitor of Interleukin-6.

Curcumin is apolyphenolic compound found in the dietary spice turmeric. Anti-inflammatory effects of turmeric have been known for centuries and extensive studies over the last two to three decades revealed that curcumin is a key component in the anti-inflammatory effects of turmeric. Chronic inflammation is involved in the various pathologic states and curcumin demonstrated therapeutic effects in different inflammation-related diseases in various in vivo, in vitro and human based studies through regulation of different signaling molecules including transcription factors, chemokines, cytokines, tumor suppressor genes, adhesion molecules and microRNAs.

Synthesis and biological evaluation of quinoline analogues of flavones as potential anticancer agents and tubulin polymerization inhibitors.

A new series of 2-aryl-trimethoxyquinoline analogues was designed and synthesized as tubulin inhibitors using methoxylated flavones as the lead compounds. The cytotoxic activity of the synthesized compounds was evaluated against four human cancer cell lines including MCF-7, MCF-7/MX, A-2780, and A-2780/RCIS. All the alcoholic derivatives (6a-6e) showed significant cytotoxic activity with IC50 in the range of 7.

Reactive Oxygen Species Mediate TNF-x237A; Cytotoxic Effects in the Multidrug-Resistant Breast Cancer Cell Line MCF-7/MX.

Background: Reactive oxygen species (ROS) are not only harmful by-products of the cellular metabolism but also essential components of cell signaling, contributing to various physiologic features including cytokine and growth factor signaling. Here, we examined the role of ROS in the cytotoxic effects of tumor necrosis factor-x237A; (TNF-x237A;) in MCF-7 cells and their drug-resistant counterparts, MCF-7/MX cells.

Materials And Methods: ROS levels were evaluated following TNF-x237A; exposure using 2',7'-dichlorodihydrofluorescein diacetate (H2DCF-DA) as fluorescent probe, and the TNF-x237A; cytotoxic effects were examined using the dimethylthiazolyl-2,5-diphenyl tetrazolium bromide (MTT) assay.

Image-Based Analysis to Predict the Activity of Tariquidar Analogs as P-Glycoprotein Inhibitors: The Importance of External Validation.

Permeability glycoprotein (P-gp) is involved in the pathology of various diseases including cancer and epilepsy, mainly through the translocation of some medicines across the cell membrane. Here, we employed image-based quantitative structure-activity relationship (QSAR) models to predict the P-gp inhibitory activity of some Tariquidar derivatives. The structures of 65 Tariquidar derivatives and their P-gp inhibition activities were collected from the literature.

MicroRNA-34a and its target genes: Key factors in cancer multidrug resistance.

Following the first small non-coding RNA identification in 1993, accumulated knowledge on the biogenesis, homeostasis and functional roles of microRNAs in different physiological and pathophysiological conditions has been discovered. MicroRNAs act through epigenetic regulation of gene expression. MiR-34a is a member of the MiR-34 family that is involved in p53 pathways, and is implicated in cell death/survival signaling.

Interleukin-6: A Critical Cytokine in Cancer Multidrug Resistance.

Multidrug resistance (MDR) is a phenomenon through which tumor cells develop resistance against the cytotoxic effects of various structurally and mechanistically unrelated chemotherapeutic agents. The most consistent feature in MDR is overexpression and/or overactivity of ATP-dependent drug efflux transporters. Other mechanisms such as overexpression of drug-detoxifying enzymes and alterations in pro-survival or pro-death signaling pathways are also responsible for MDR.

Highly Oxygenated Sesquiterpene Lactones from Cousinia aitchisonii and their Cytotoxic Properties: Rhaserolide Induces Apoptosis in Human T Lymphocyte (Jurkat) Cells via the Activation of c-Jun n-terminal Kinase Phosphorylation.

Infrared-guided chromatographic fractionation of sesquiterpene lactones from the extracts of Cousinia aitchisonii and Cousinia concolor led to the isolation of five pure compounds. A new sesquiterpene lactone, namely, aitchisonolide, and two known sesquiterpene lactones (desoxyjanerin and rhaserolide) were isolated from C. aitchisonii and two known lignans (arctiin and arctigenin) from C.

TNF-α exerts higher cytotoxic effect on MCF-7 multidrug resistant derivative, role of Akt activation.

Background: TNF-α is a pleiotropic cytokine which activates different downstream signaling pathways leading cells to death or survival. In some in vitro examinations, TNF-α treatment demonstrated higher cytotoxic effects on MDR cancer cell lines compared to their parental counterparts.

Objective: This study investigated effects of TNF-α in MCF-7 and its mitoxantrone (MX) resistant variant of breast cancer cell line, MCF-7/MX.

Reversal of P-glycoprotein-mediated multidrug resistance in MCF-7/Adr cancer cells by sesquiterpene coumarins.

In the present study, fifteen sesquiterpene coumarins were isolated and purified from different Ferula species, and were tested for their MDR reversal properties. Enhancement of doxorubicin cytotoxicity in MCF-7/Adr cells (doxorubicin resistant derivatives of MCF-7 cells overexpressing P-gp), when combined with very non-toxic concentrations of the sesquiterpene coumarins (50 μM) including umbelliprenin, farnesiferol B, farnesiferol C and lehmferin, proved significant MDR reversal activity of these coumarins. Flow cytometric efflux assay confirmed that the intracellular accumulation of Rho123 was significantly increased in MCF-7/Adr cells when treated with sesquiterpene coumarins.

Synthesis and biological evaluation of novel pyridine derivatives as potential anticancer agents and phosphodiesterase-3 inhibitors.

Phosphodiesterases (PDEs) have been studied in a variety of tumours; data have suggested that the levels of PDE activities are elevated and, therefore, the ratios of cGMP to cAMP are affected. In addition, PDE inhibitors are potential targets for tumour cell growth inhibition and induction of apoptosis. Nonselective PDE inhibitors, such as theophylline or aminophylline, are known regulators of growth in a variety of carcinoma cell lines, suggesting a potential role for PDE inhibitors as anticancer drugs.

Investigation of the antibacterial activity and efflux pump inhibitory effect of co-loaded piperine and gentamicin nanoliposomes in methicillin-resistant Staphylococcus aureus.

Objective: Antibiotic resistance has stimulated the research for developing novel strategies that can prevent bacterial growth. Methicillin-resistant Staphylococcus aureus (MRSA), regarded as one of the most serious antibiotic-resistant bacteria which has been conventionally recognized as a nosocomial pathogen.

Materials And Methods: Nanoliposomal formulations of piperine and gentamicin were prepared by dehydration-rehydration (DRV) method and characterized for size, zeta potential and encapsulation efficiency.

Synthesis, Anti-Inflammatory and Anti- Nociceptive Activities and Cytotoxic Effect of Novel Thiazolidin-4-ones Derivatives as Selective Cyclooxygenase (COX-2) Inhibitors.

Objective(s): Nowadays, COX - 2 inhibitors such as valdecoxib are removed from the market because of their cardiovascular toxicity and their potential to increase the risk of strokes. In response to this, medicinal chemists have attempted to synthesize new classes of COX-2 Inhibitors.

Materials And Methods: In this study, three novel analogues of thiazolidin-4-ones derivatives 2a-c were synthesized.

Synthesis and molecular modeling of six novel monastrol analogues: evaluation of cytotoxicity and kinesin inhibitory activity against HeLa cell line.

Background And The Purpose Of The Study: A common approach in cancer chemotherapy is development of drugs that interrupt the mitosis phase of cell division. Dimethylenastron is a known kinesin inhibitor. In this study, six novel dimethylenastron analogues (4a-f), in which 3-hydroxyphenyl substituent has been replaced with substituted benzylimidazolyl, were synthesized through Biginelli reaction.