Search results for "pharmacogenomic"
showing 10 items of 59 documents
Betulinic Acid Exerts Cytotoxic Activity Against Multidrug-Resistant Tumor Cells via Targeting Autocrine Motility Factor Receptor (AMFR).
2018
Betulinic acid (BetA) is a naturally occurring pentacyclic triterpene isolated from the outer bark of white-barked birch trees and many other medicinal plants. Here, we studied betulinic acid's cytotoxic activity against drug-resistant tumor cell lines. P-glycoprotein (MDR1/ABCB1) and BCRP (ABCG2) are known ATP-binding cassette (ABC) drug transporters that mediating MDR. ABCB5 is a close relative to ABCB1, which also mediates MDR. Constitutive activation of the EGF receptor is tightly linked to the development of chemotherapeutic resistance. BetA inhibited P-gp, BCRP, ABCB5 and mutation activated EGFR overexpressing cells with similar efficacy as their drug-sensitive parental counterparts. …
Repurposing of Bromocriptine for Cancer Therapy
2018
Bromocriptine is an ergot alkaloid and dopamine D2 receptor agonist used to treat Parkinson’s disease, acromegaly, hyperprolactinemia, and galactorrhea, and more recently diabetes mellitus. The drug is also active against pituitary hormone-dependent tumors (prolactinomas and growth-hormone producing adenomas). We investigated, whether bromocriptine also inhibits hormone-independent and multidrug-resistant (MDR) tumors. We found that bromocriptine was cytotoxic towards drug-sensitive CCRF-CEM, multidrug-resistant CEM/ADR5000 leukemic cells as well as wild-type or multidrug-resistant ABCB5-transfected HEK293 cell lines, but not sensitive or BCRP-transfected multidrug-resistant MDA-MB-231 brea…
Molecular Determinants of Sensitivity or Resistance of Cancer Cells Toward Sanguinarine.
2018
For decades, natural products represented a significant source of diverse and unique bioactive lead compounds in drug discovery field. In Clinical oncology, complete tumors remission is hampered by the development of drug-resistance. Therefore, development of cytotoxic agents that may overcome drug resistance is urgently needed. Here, the natural benzophenanthridine alkaloid sanguinarine has been studied for its cytotoxic activity against multidrug resistance (MDR) cancer cells. We investigated the role of the ATP-binding cassette (ABC) transporters BCRP/ABCG2, P-glycoprotein/ABCB1 and its close relative ABCB5 in drug resistance. Further drug resistance mechanisms analyzed in this study wer…
Multifactorial Modes of Action of Arsenic Trioxide in Cancer Cells as Analyzed by Classical and Network Pharmacology
2018
Arsenic trioxide is a traditional remedy in Chinese Medicine since ages. Nowadays, it is clinically used to treat acute promyelocytic leukemia (APL) by targeting PML/RARA. However, the drug’s activity is broader and the mechanisms of action in other tumor types remain unclear. In this study, we investigated molecular modes of action by classical and network pharmacological approaches. CEM/ADR5000 resistance leukemic cells were similar sensitive to As2O3 as their wild-type counterpart CCRF-CEM (resistance ratio: 1.88). Drug-resistant U87.MG ΔEGFR glioblastoma cells harboring mutated epidermal growth factor receptor were even more sensitive (collateral sensitive) than wild-type U87.MG cells (…
Drug Repurposing of the Anthelmintic Niclosamide to Treat Multidrug-Resistant Leukemia
2017
Multidrug resistance, a major problem that leads to failure of anticancer chemotherapy, requires the development of new drugs. Repurposing of established drugs is a promising approach for overcoming this problem. An example of such drugs is niclosamide, a known anthelmintic that is now known to be cytotoxic and cytostatic against cancer cells. In this study, niclosamide showed varying activity against different cancer cell lines. It revealed better activity against hematological cancer cell lines CCRF-CEM, CEM/ADR5000, and RPMI-8226 compared to the solid tumor cell lines MDA-MB-231, A549, and HT-29. The multidrug resistant CEM/ADR5000 cells were similar sensitive as their sensitive counterp…
As-needed anti-inflammatory reliever therapy for asthma management: evidence and practical considerations
2021
Asthma is a chronic respiratory disease in which airway inflammation is a key feature, even in the milder expressions of the disease. The conventional pharmacological approach to mild asthma has long relied on reliever therapy with as-needed short-acting beta-agonists (SABAs), while anti-inflammatory maintenance with inhaled corticosteroids (ICSs) has been reserved for patients with more persistent asthma. Poor adherence to maintenance treatment is an important issue in asthma management, and can partly explain suboptimal symptom control. Over-reliance on SABA bronchodilators for rapid symptom relief is common in real life and potentially leads to an increased risk of asthma morbidity and m…
Oridonin Targets Multiple Drug-Resistant Tumor Cells as Determined by in Silico and in Vitro Analyses
2018
Drug resistance is one of the main reasons of chemotherapy failure. Therefore, overcoming drug resistance is an invaluable approach to identify novel anticancer drugs that have the potential to bypass or overcome resistance to established drugs and to substantially increase life span of cancer patients for effective chemotherapy. Oridonin is a cytotoxic diterpenoid isolated from Rabdosia rubescens with in vivo anticancer activity. In the present study, we evaluated the cytotoxicity of oridonin toward a panel of drug-resistant cancer cells overexpressing ABCB1, ABCG2, or ΔEGFR or with a knockout deletion of TP53. Interestingly, oridonin revealed lower degree of resistance than the control dr…
I10 The anticancer activity of the antimalarial artesunate
2017
More than a decade ago, we initiated a research program on the molecular pharmacology of phytochemicals derived from Chinese medicinal herbs. A promising compound was artemisinin from Artemisia annua L. and its semisynthetic compound artesunate [1] . Artemisinin and artesunate are anti-malarial drugs. Our data indicated profound activity against cancer cells, but also against various viruses, Schistosoma, Trypanosoma, and even plant crown gall tumors. To elucidate the molecular mode of actions against cancer, we applied molecular biological and pharmacogenomic approaches in vitro and in vivo. Different signalling pathways were identified not only in cancer cells but also in cells infected w…
Involvement of non-coding RNAs in chemo- and radioresistance of colorectal cancer
2016
Despite recent progress in understanding the cancer signaling pathways and in developing new therapeutic strategies, however, the resistance of colorectal cancer (CRC) cells to chemo- and radiotherapy represents the main hurdle to the successful treatment, leading to tumor recurrence and, consequently, a poor prognosis. Therefore, overcoming drug and radiation resistance, enhancing drug and radiation sensitivity of CRC cells, and improving the effi cacy of chemo- and radiotherapy have an important signifi cance in the treatment of CRC. The identifi cation of new molecular biomarkers which can predict therapy response and prognosis is one of the most signifi cant aims in pharmacogenomics and…
Usefulness of current candidate genetic markers to identify childhood cancer patients at risk for platinum-induced ototoxicity: Results of the Europe…
2020
Background Irreversible sensorineural hearing loss is a common side effect of platinum treatment with the potential to significantly impair the neurocognitive, social and educational development of childhood cancer survivors. Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in the FDA drug label and a pharmacogenetic guideline. The aim of this cross-sectional cohort study was to confirm the genetic associations in a large pan-European population and to evaluate the diagnostic accuracy of the genetic…