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Investigational New Drugs
Published in: Investigational New Drugs 6/2017

01-12-2017 | PRECLINICAL STUDIES

Induction of accelerated senescence by the microtubule-stabilizing agent peloruside A

Authors: Ariane Chan, Connie Gilfillan, Nikki Templeton, Ian Paterson, Peter T. Northcote, John H. Miller

Published in: Investigational New Drugs | Issue 6/2017

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Summary

Chemotherapeutic agents can induce accelerated senescence in tumor cells, an irreversible state of cell cycle arrest. Paclitaxel, a microtubule-stabilizing agent used to treat solid tumors of the breast, ovary, and lung and discodermolide, another stabilizing agent from a marine sponge, induce senescence in cultured cancer cells. The aim of this study was to determine if the microtubule-stabilizing agent peloruside A, a polyketide natural product from a marine sponge, can induce accelerated senescence in a breast cancer cell line MCF7. Doxorubicin, a DNA-damaging agent, paclitaxel, and discodermolide were used as positive controls. Senescence-associated-β-galactosidase activity was increased by peloruside A, similar to paclitaxel, discodermolde, and doxorubicin, with a potency heirarchy of doxorubicin > paclitaxel > discodermolide > peloruside, based on IC25 concentrations that inhibit proliferation. Clonogenic survival was significantly decreased by peloruside A, similar to doxorubicin and the two other microtubule-stabilizing agents. The tumor suppressor protein p53 increased after treatment, whereas pRb decreased in response to all four compounds. It was concluded that in addition to apoptosis, peloruside A causes accelerated senescence in a subpopulation of MCF7 cells that contributes to its potential anticancer activity in a breast cancer cell line.
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Metadata
Title
Induction of accelerated senescence by the microtubule-stabilizing agent peloruside A
Authors
Ariane Chan
Connie Gilfillan
Nikki Templeton
Ian Paterson
Peter T. Northcote
John H. Miller
Publication date
01-12-2017
Publisher
Springer US
Published in
Investigational New Drugs / Issue 6/2017
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-017-0493-5

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