Universal response in the RKO colon cancer cell line to distinct antimitotic therapies

Alexander Lorz; Dana-Adriana Botesteanu; Doron Levy

doi:10.1038/s41598-018-27267-7

Universal response in the RKO colon cancer cell line to distinct antimitotic therapies

Alexander Lorz, Dana-Adriana Botesteanu, Doron Levy

Computer, Electrical and Mathematical Sciences and Engineering

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1 Scopus citations

Abstract

Both classic and newer antimitotics commonly induce a prolonged mitotic arrest in cell culture. During arrest, cells predominantly undergo one of two fates: cell death by apoptosis, or mitotic slippage and survival. To refine this binary description, a quantitative understanding of these cell responses is needed. Herein, we propose a quantitative description of the kinetics of colon carcinoma RKO cell fates in response to different antimitotics, using data from the single cell experiments of Gascoigne and Taylor (2008). The mathematical model is calibrated using the in vitro experiments of Gascoigne and Taylor (2008). We show that the time-dependent probability of cell death or slippage is universally identical for monastrol, nocodazole and two different doses of AZ138, but significantly different for taxol. Death and slippage responses across drugs can be characterized by Gamma distributions. We demonstrate numerically that these rates increase with prolonged mitotic arrest. Our model demonstrates that RKO cells exhibit a triphasic response - first, remain in mitosis, then undergo fast and slow transition, respectively- dependent on the length of mitotic arrest and irrespective of cell fate, drug type or dose.

Original language	English (US)
Journal	Scientific Reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-27267-7
State	Published - Jun 12 2018

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): BAS/1/1648-01-01, BAS/1/1648-01-02
Acknowledgements: The work of AL was supported by the King Abdullah University of Science and Technology (KAUST) baseline and start-up funds (BAS/1/1648-01-01 and BAS/1/1648-01-02). The work of DAB was partially supported by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute as part of a seed grant from the UMD-NCI Partnership for Cancer Technology. The work of DL was supported in part by the National Science Foundation under Grant Number DMS-1713109 and the Jayne Koskinas Ted Giovanis Foundation. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

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10.1038/s41598-018-27267-7

https://repository.kaust.edu.sa/bitstream/10754/628447/1/s41598-018-27267-7.pdf

Cite this

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title = "Universal response in the RKO colon cancer cell line to distinct antimitotic therapies",

abstract = "Both classic and newer antimitotics commonly induce a prolonged mitotic arrest in cell culture. During arrest, cells predominantly undergo one of two fates: cell death by apoptosis, or mitotic slippage and survival. To refine this binary description, a quantitative understanding of these cell responses is needed. Herein, we propose a quantitative description of the kinetics of colon carcinoma RKO cell fates in response to different antimitotics, using data from the single cell experiments of Gascoigne and Taylor (2008). The mathematical model is calibrated using the in vitro experiments of Gascoigne and Taylor (2008). We show that the time-dependent probability of cell death or slippage is universally identical for monastrol, nocodazole and two different doses of AZ138, but significantly different for taxol. Death and slippage responses across drugs can be characterized by Gamma distributions. We demonstrate numerically that these rates increase with prolonged mitotic arrest. Our model demonstrates that RKO cells exhibit a triphasic response - first, remain in mitosis, then undergo fast and slow transition, respectively- dependent on the length of mitotic arrest and irrespective of cell fate, drug type or dose.",

author = "Alexander Lorz and Dana-Adriana Botesteanu and Doron Levy",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledged KAUST grant number(s): BAS/1/1648-01-01, BAS/1/1648-01-02 Acknowledgements: The work of AL was supported by the King Abdullah University of Science and Technology (KAUST) baseline and start-up funds (BAS/1/1648-01-01 and BAS/1/1648-01-02). The work of DAB was partially supported by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute as part of a seed grant from the UMD-NCI Partnership for Cancer Technology. The work of DL was supported in part by the National Science Foundation under Grant Number DMS-1713109 and the Jayne Koskinas Ted Giovanis Foundation. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript",

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N2 - Both classic and newer antimitotics commonly induce a prolonged mitotic arrest in cell culture. During arrest, cells predominantly undergo one of two fates: cell death by apoptosis, or mitotic slippage and survival. To refine this binary description, a quantitative understanding of these cell responses is needed. Herein, we propose a quantitative description of the kinetics of colon carcinoma RKO cell fates in response to different antimitotics, using data from the single cell experiments of Gascoigne and Taylor (2008). The mathematical model is calibrated using the in vitro experiments of Gascoigne and Taylor (2008). We show that the time-dependent probability of cell death or slippage is universally identical for monastrol, nocodazole and two different doses of AZ138, but significantly different for taxol. Death and slippage responses across drugs can be characterized by Gamma distributions. We demonstrate numerically that these rates increase with prolonged mitotic arrest. Our model demonstrates that RKO cells exhibit a triphasic response - first, remain in mitosis, then undergo fast and slow transition, respectively- dependent on the length of mitotic arrest and irrespective of cell fate, drug type or dose.

AB - Both classic and newer antimitotics commonly induce a prolonged mitotic arrest in cell culture. During arrest, cells predominantly undergo one of two fates: cell death by apoptosis, or mitotic slippage and survival. To refine this binary description, a quantitative understanding of these cell responses is needed. Herein, we propose a quantitative description of the kinetics of colon carcinoma RKO cell fates in response to different antimitotics, using data from the single cell experiments of Gascoigne and Taylor (2008). The mathematical model is calibrated using the in vitro experiments of Gascoigne and Taylor (2008). We show that the time-dependent probability of cell death or slippage is universally identical for monastrol, nocodazole and two different doses of AZ138, but significantly different for taxol. Death and slippage responses across drugs can be characterized by Gamma distributions. We demonstrate numerically that these rates increase with prolonged mitotic arrest. Our model demonstrates that RKO cells exhibit a triphasic response - first, remain in mitosis, then undergo fast and slow transition, respectively- dependent on the length of mitotic arrest and irrespective of cell fate, drug type or dose.

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Universal response in the RKO colon cancer cell line to distinct antimitotic therapies

Abstract

Bibliographical note

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