Aplidin-resistant IGROV-1/APL cells were derived from the human ovarian cancer IGROV-1 cell line by exposing the cells to increasing concentration of Aplidin for eight months, starting from a concentration of 10 nM to a final concentration of 4 microM. IGROV-1/APL cell line possesses five fold relative resistance to Aplidin. IGROV-1/APL resistant cell line shows the typical MDR phenotype: (1) increased expression of membrane-associated P-glycoprotein, (2) cross-resistance to drugs like etoposide, doxorubicin, vinblastine, vincristine, taxol, colchicin and the novel anticancer drug Yondelis (ET-743). The Pgp inhibitor cyclosporin-A restored the sensitivity of IGROV-1/APL cells to Aplidin by increasing the drug intracellular concentration. The resistance to Aplidin was not due to the other proteins, such as LPR-1 and MRP-1, being expressed at the same level in resistant and parental cell line. The finding that cells over-expressing Pgp are resistant to Aplidin was confirmed in CEM/VLB 100 cells, that was found to be 5-fold resistant to Aplidin compared to the CEM parental cell line.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.4161/cbt.4.12.2157 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Marine Cyclic Peptides: Antimicrobial Activity and Synthetic Strategies.
Mar Drugs
June 2022
Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
Oceans are a rich source of structurally unique bioactive compounds from the perspective of potential therapeutic agents. Marine peptides are a particularly interesting group of secondary metabolites because of their chemistry and wide range of biological activities. Among them, cyclic peptides exhibit a broad spectrum of antimicrobial activities, including against bacteria, protozoa, fungi, and viruses.
View Article and Find Full Text PDFPreclinical Activity of Plitidepsin Against Clear Cell Carcinoma of the Ovary.
Anticancer Res
September 2021
Department of Obstetrics and Gynecology, Nara Medical University, Nara, Japan
Background/aim: To evaluate the antitumor effects of Plitidepsin against clear cell carcinoma (CCC) of the ovary.
Materials And Methods: The expression of eEF1A2 in ovarian cancer was assessed by immunohistochemistry. Using ovarian CCC cell lines, the antitumor effect of Plitidepsin was assessed both in vitro and in vivo.
There is an urgent need to identify therapeutics for the treatment of Coronavirus disease 2019 (COVID-19). Although different antivirals are given for the clinical management of SARS-CoV-2 infection, their efficacy is still under evaluation. Here, we have screened existing drugs approved for human use in a variety of diseases, to compare how they counteract SARS-CoV-2-induced cytopathic effect and viral replication Among the potential 72 antivirals tested herein that were previously proposed to inhibit SARS-CoV-2 infection, only 18 % had an IC below 25 µM or 10 IU/ml.
View Article and Find Full Text PDFHost-directed therapies against early-lineage SARS-CoV-2 retain efficacy against B.1.1.7 variant.
bioRxiv
February 2021
Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG), San Francisco, CA 94158, USA.
Article Synopsis
- COVID-19, caused by the virus SARS-CoV-2, has led to millions of deaths and significant global challenges, with a new concerning variant named B.1.1.7 emerging from the UK.
- Research has shown that host-directed therapies, like plitidepsin and ralimetinib, may be effective against both the original virus and the new variant, showing promise against resistance.
- Plitidepsin is notably more potent than remdesivir in treating these viral infections, emphasizing the need to develop host-targeted treatments to manage current and future coronavirus outbreaks.
Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A.
Science
February 2021
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins interact with the eukaryotic translation machinery, and inhibitors of translation have potent antiviral effects. We found that the drug plitidepsin (aplidin), which has limited clinical approval, possesses antiviral activity (90% inhibitory concentration = 0.88 nM) that is more potent than remdesivir against SARS-CoV-2 in vitro by a factor of 27.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!