Search results for "drug resistance"

The broad-spectrum antiinfective drug artesunate interferes with the canonical nuclear factor kappa B (NF-κB) pathway by targeting RelA/p65.

2015

Infection with human cytomegalovirus (HCMV) is a serious medical problem, particularly in immunocompromised individuals and neonates. The success of standard antiviral therapy is hampered by low drug compatibility and induction of viral resistance. A novel strategy is based on the exploitation of cell-directed signaling inhibitors. The broad antiinfective drug artesunate (ART) offers additional therapeutic options such as oral bioavailability and low levels of toxic side-effects. Here, novel ART-derived compounds including dimers and trimers were synthesized showing further improvements over the parental drug. Antiviral activity and mechanistic aspects were determined leading to the followi…

Utilizing inherent fluorescence of therapeutics to analyze real-time uptake and multi-parametric effector kinetics.

2011

Abstract The precise detection of pharmaceutical drug uptake and knowledge of a drug’s efficacy at the single-cell level is crucial for understanding a compound’s performance. Many pharmaceutical drugs, like the model substances Doxorubicin, Mitoxantrone or Irinotecan, have a distinctive natural fluorescence that can be readily exploited for research purposes. Utilizing this respective natural fluorescence, we propose a method analyzing simultaneously in real-time the efficiency, effects and the associated kinetics of compound-uptake and efflux in mammalian cells by flow cytometry. We show that real-time flow cytometric quantification of compound-uptake is reliably measured and that analyzi…

Impact of microRNAs in Resistance to Chemotherapy and Novel Targeted Agents in Non-Small Cell Lung Cancer

2014

Despite recent advances in understanding the cancer signaling pathways and in developing new therapeutic strategies, non-small cell lung cancer (NSCLC) shows grim prognosis and high incidence of recurrence. Insufficient dis- ruption of oncogenic signaling and drug resistance are the most common causes of tumor recurrence. Drug resistance, in- trinsic or acquired, represents a main obstacle in NSCLC therapeutics by limiting the efficacy both of conventional che- motherapeutic compounds and new targeted agents. Therefore, novel and more innovative approaches are required for treatment of this tumor. MicroRNAs (miRNAs) are a family of small non-coding RNAs that regulate gene expression by sequ…

Commentary. Regulation of drug and immune resistance by YY1 in cancer.

2010

Therapeutic targeting of SNAIL, RKIP, and YY1 in tumor metastasis and drug resistance

2020

Abstract Cancer is the leading cause of deaths worldwide and is of great importance. Metastasis-inducing the majority of cancer related deaths is a principal problem in cancer treatment. Therefore, therapy regimes preventing metastasis formation are of prominent importance to improve the outcome of malignant diseases. The epithelial-mesenchymal transition (EMT) is a predominant process associated with the onset of metastasis and converts epithelial cells to mesenchymal cells. In this chapter, we concentrated on three proteins involved in the metastasis and EMT: RKIP, SNAIL, and YY1. Briefly, SNAIL and YY1 are overexpressed in many cancers, while RKIP is downregulated. Therefore, these prote…

Identification of chemosensitizers by drug repurposing to enhance the efficacy of cancer therapy

2020

Abstract The progressively rising drug resistance has driven the development of chemosensitizers, which aim to enhance the current chemotherapeutic efficacy through either quantitatively increasing intracellular drug concentration by inhibiting drug efflux, vesicle sequestration, and metabolic inactivation or qualitatively exerting concomitant effects on cellular regulation to promote apoptosis. Given the high failure rates and costs during standard drug development, drug repurposing represents an effective and economic approach for chemosensitizer identification. By applying drug repurposing, a wide range of existing clinic drugs including anticardiovascular agents, immunosuppressants, ant…

Relevance of Multidrug Resistance Proteins on the Clinical Efficacy of Cancer Therapy

2005

Variations in drug uptake and efflux, as well as changes in intracellular drug entrapment and distribution may represent important resistance mechanisms to cancer therapy. A variety of ATP binding cassette transporters (ABC) localised in multiple cell membranes is implied in those phenomena, representing a mechanism of protection of cells against xenobiotics. Many cancer cell lines over express some ABC transporters, especially p-glycoprotein, MRP1 and BCRP. This over expression is related to worse cancer treatment outcome and, in some cases, reduced overall survival of cancer patients. This paper reviews the location and physiological role of the three transporters mentioned and also descr…

Selected Secondary Plant Metabolites for Cancer Therapy

2015

Secondary plant metabolites reveal numerous biological activities making them attractive as resource for drug development of human diseases. As the majority of cancer drugs clinically established during the past half century is derived from nature, cancer researchers worldwide try to identify novel natural products as lead compounds for cancer therapy. Natural products are considered as promising cancer therapeutics, either as single agents or in combination protocols, to enhance the antitumor activity of additional therapeutic modalities. Most natural compounds exert pleotrophic effects and modulate various signal transduction pathways. A better understanding of the complex mechanisms of a…

Molecular interaction of artemisinin with translationally controlled tumor protein (TCTP) of Plasmodium falciparum

2012

Malaria causes millions of death cases per year. Since Plasmodium falciparum rapidly develops drug resistance, it is of high importance to investigate potential drug targets which may lead to novel rational therapy approaches. Here we report on the interaction of translationally controlled tumor protein of P. falciparum (PfTCTP) with the anti-malarial drug artemisinin. Furthermore, we investigated the crystal structure of PfTCTP. Using mass spectrometry, bioinformatic approaches and surface plasmon resonance spectroscopy, we identified novel binding sites of artemisinin which are in direct neighborhood to amino acids 19-46, 108-134 and 140-163. The regions covered by these residues are know…

Antitumor Effect of Glandora rosmarinifolia (Boraginaceae) Essential Oil through Inhibition of the Activity of the Topo II Enzyme in Acute Myeloid Le…

2022

It was previously shown that the antitumor and cytotoxic activity of the essential oil (EO) extracted from the aerial parts of Glandora rosmarinifolia appears to involve a pro-oxidant mechanism in hepatocellular carcinoma (HCC) and in triple-negative breast cancer (TNBC) cell lines. Its most abundant compound is a hydroxy-methyl-naphthoquinone isomer. Important pharmacological activities, such as antitumor, antibacterial, antifungal, antiviral and antiparasitic activities, are attributed to naphthoquinones, probably due to their pro-oxidant or electrophilic potential; for some naphthoquinones, a mechanism of action of topoisomerase inhibition has been reported, in which they appear to act b…