UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Thompson Lab

Publication Date

2017-05-09

Document Type

Article

Disciplines

Biochemistry | Cancer Biology | Enzymes and Coenzymes | Medicinal and Pharmaceutical Chemistry | Medicinal Chemistry and Pharmaceutics | Molecular Biology | Oncology

Abstract

Microvesicle (MV) release from tumour cells influences drug retention, contributing to cancer drug resistance. Strategically regulating MV release may increase drug retention within cancer cells and allow for lower doses of chemotherapeutic drugs. The contribution of exosomes to drug retention still remains unknown. Potential exosome and MV (EMV) biogenesis inhibitors, tested on human prostate cancer (PC3) cells for their capacity to inhibit EMV release, were also tested on PC3 and MCF-7 (breast cancer) cells for improving chemotherapy. Agents inhibiting EMV release most significantly, whilst maintaining cell viability, were chloramidine (Cl-amidine; 50 microM) and bisindolylmaleimide-I (10 microM). Apoptosis mediated by the chemotherapy drug 5-fluorouracil (5-FU) was significantly enhanced in PC3 cells in the presence of both these EMV inhibitors, resulting in a 62% (Cl-amidine + 5-FU) and 59% (bisindolylmaleimide-I + 5-FU) decrease in numbers of viable PC3 cells compared to 5-FU alone after 24 h. For MCF-7 cells, there were similar increased reductions of viable cells compared to 5-FU treatment alone ranging from 67% (Cl-amidine + 5-FU) to 58% (bisindolylmaleimide-I + 5-FU). Using combinatory treatment, the two EMV inhibitors further reduced the number of viable cancer cells tested. Neither inhibitor affected cell viability. Combining selected EMV inhibitors may pose as a novel strategy to enhance the efficacy of chemotherapeutic drug-mediated apoptosis.

Keywords

5-fluorouracil, bisindolylmaleimide-I, chloramidine, drug retention, exosomes, microvesicles, multidrug resistance, peptidylarginine deiminase, prostate cancer

Rights and Permissions

Copyright © 2017 by the authors. Licensee MDPI, Basel, Switzerland.

DOI of Published Version

10.3390/ijms18051007

Source

Int J Mol Sci. 2017 May 9;18(5). pii: E1007. doi: 10.3390/ijms18051007. Link to article on publisher's site

Journal/Book/Conference Title

International journal of molecular sciences

Related Resources

Link to Article in PubMed

PubMed ID

28486412

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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