Inhibitors of microvesicle release with the potential to enhance effectivity of cancer chemotherapy

Jameel Inal, Uchini S Kosgodage, Sigrun Lange

Research output: Contribution to conferencePosterpeer-review

Abstract

Introduction: Microvesicle (MV) release from tumour cells plays an important role in cancer drug resistance. It is essential that chemotherapeutic drugs are retained within target cells for increased effectiveness in inducing apoptosis. Microvesiculation influences drug retention so minimizing drug efflux is important. Based on MV biogenesis pathways, a range of potential inhibitors were tested.

Methods: The NanoSight LM10 was used to analyse MV release from PC3 human prostate cancer cells. Cells were maintained in serumfree RPMI 1640. Washed cells were seeded in triplicate at 3.8105 cells/well initially treated with 300 mM BzATP for 1 h, and further 1 h with relevant concentrations of MV-inhibitors. MV count, annexin V staining and cell viability were assessed.

Results: The numbers of MVs released were compared to control (BzATP alone). Up to 60% clear inhibition of MV release was shown with all reagents used. The maximum MV inhibition was with 500 mM ethylene glycol tetraacetic acid (EGTA) and 10 mM bisindolymaleimide I, resulting in 48 and 34%, respectively. Cell viability was 80% in all cases except for panthethine, which only resulted in 25%. Annexin V staining confirmed the vesicles identified were indeed MVs.

Summary/conclusion: EGTA and bisindolymaleimide I are potent inhibitors of MV release. Both novel and classic reagents described may be used individually or in combination. This could be similar to calpeptin and chloramidine, which enabled prostate cancer cells to sensitize to docetaxel treatment previously. This study extends the range of inhibitors that can be utilized to enhance novel combinatory treatment options.
Original languageEnglish
Pages29-29
Number of pages1
Publication statusPublished - 30 May 2016
EventThe Fifth International Meeting of ISEV, ISEV2016,
Rotterdam, The Netherlands, 4 – 7 May, 2016: ISEV annual meeting, 2016
- Rotterdam, Netherlands
Duration: 4 May 20167 May 2016
http://www.isev.org/page/isev2016

Conference

ConferenceThe Fifth International Meeting of ISEV, ISEV2016,
Rotterdam, The Netherlands, 4 – 7 May, 2016
Abbreviated titleISEV, 2016
Country/TerritoryNetherlands
CityRotterdam
Period4/05/167/05/16
Internet address

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