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Updated: Jan 3, 2026
A Time-lapse, Label-free, Quantitative Phase Imaging Study of Dormant and Active Human Cancer Cells
Published on: February 16, 2018
Identifying fates of cancer cells exposed to mitotic inhibitors by quantitative phase imaging
Dian Huang1, Irena J Roy, Graeme F Murray
1Department of Bioengineering, University of California, Los Angeles, CA 90095, USA. mteitell@mednet.ucla.edu.
Abstract:
Cell cycle deregulation is a cancer hallmark that has stimulated the development of mitotic inhibitors with differing mechanisms of action. Quantitative phase imaging (QPI) is an emerging approach for determining cancer cell sensitivities to chemotherapies in vitro. Cancer cell fates in response to mitotic inhibitors are agent- and dose-dependent. Fates that lead to chromosomal instabilities may result in a survival advantage and drug resistance. Conventional techniques for quantifying cell fates are incompatible with growth inhibition assays that produce binary live/dead results. Therefore, we used QPI to quantify post-mitotic fates of G0/G1 synchronized HeLa cervical adenocarcinoma and M202 melanoma cells during 24 h of escalating-dose exposures to mitotic inhibitors, including microtubule inhibitors paclitaxel and colchicine, and an Aurora kinase A inhibitor, VX-680. QPI determined cell fates by measuring changes in cell biomass, morphology, and mean phase-shift. Cell fates fell into three groups: (1) bipolar division from drug failure; (2) cell death or sustained mitotic arrest; and (3) aberrant endocycling or multipolar division. In this proof-of-concept study, colchicine was most effective in producing desirable outcomes of sustained mitotic arrest or death throughout its dosing range, whereas both paclitaxel and VX-680 yielded dose-dependent multipolar divisions or endocycling, respectively. Furthermore, rapid completion of mitosis associated with bipolar divisions whereas prolonged mitosis associated with multipolar divisions or cell death. Overall, QPI measurement of drug-induced cancer cell fates provides a tool to inform the development of candidate agents by quantifying the dosing ranges over which suboptimal inhibitor choices lead to undesirable, aberrant cancer cell fates.
Insights
Quantitative phase imaging (QPI) effectively measures cancer cell fates after mitotic inhibitor treatment. Colchicine showed promise by inducing cell death or arrest, unlike other agents that caused aberrant cell divisions.
Area of Science:
- Cell biology
- Cancer research
- Quantitative imaging
Background:
- Cell cycle deregulation is a key hallmark of cancer, driving the development of mitotic inhibitors.
- Quantitative phase imaging (QPI) is an emerging technology for assessing cancer cell responses to chemotherapy in vitro.
- Traditional methods for quantifying cell fates are limited, especially in growth inhibition assays yielding binary live/dead results.
Purpose of the Study:
- To utilize QPI for quantifying post-mitotic cell fates in response to various mitotic inhibitors.
- To compare the efficacy of different mitotic inhibitors (paclitaxel, colchicine, VX-680) in inducing specific cancer cell fates.
- To establish QPI as a tool for informing the development of novel anti-cancer agents.
Main Methods:
- G0/G1 synchronized HeLa and M202 cancer cells were exposed to escalating doses of paclitaxel, colchicine, and VX-680 over 24 hours.
- Quantitative phase imaging (QPI) was employed to measure changes in cell biomass, morphology, and mean phase-shift.
- Cell fates were categorized into bipolar division, cell death/mitotic arrest, or aberrant endocycling/multipolar division.
Main Results:
- Colchicine demonstrated the most effectiveness, inducing sustained mitotic arrest or cell death across its dosing range.
- Paclitaxel and VX-680 showed dose-dependent induction of undesirable fates, including multipolar divisions and endocycling, respectively.
- Rapid mitosis correlated with bipolar divisions, while prolonged mitosis was associated with multipolar divisions or cell death.
Conclusions:
- QPI provides a valuable method for quantifying drug-induced cancer cell fates, offering insights beyond simple live/dead assays.
- The study highlights colchicine's potential for inducing favorable cell fates (arrest/death) compared to paclitaxel and VX-680.
- This approach can guide the selection of anti-cancer agents by identifying dosing ranges that avoid aberrant cell fates.
