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Updated: Aug 23, 2026
Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel
Published on: May 14, 2018
Paclitaxel induces primary and postmitotic G1 arrest in human arterial smooth muscle cells
Mikhail V Blagosklonny1, Zbigniew Darzynkiewicz, H Dorota Halicka
1Brander Cancer Research Institute, New York Medical College, Hawthorne, New York, USA.
Abstract:
Paclitaxel (PTX), a microtubule-active drug, causes mitotic arrest leading to apoptosis in certain tumor cell lines. Here we investigated the effects of PTX on human arterial smooth muscle cell (SMC) cells. In SMC, PTX caused both (a) primary arrest in G(1) and (b) post-mitotic arrest in G(1). Post-mitotic cells were multinucleated (MN) with either 2C (near-diploid) or 4C (tetraploid) DNA content. At PTX concentrations above 12 ng/ml, MN cells had 4C DNA content consistent with the lack of cytokinesis during abortive mitosis. Treatment with 6-12 ng/ml PTX yielded MN cells with 2C DNA content. Finally, 1-6 ng/ml of PTX, the lowest concentrations that affected cell proliferation, caused G(1) arrest without multinucleation. It is important that PTX did not cause apoptosis in SMC. The absence of apoptosis could be explained by mitotic exit and G(1) arrest as well as by low constitutive levels of caspase expression and by p53 and p21 induction. Thus, following transient mitotic arrest, SMC exit mitosis to form MN cells. These post-mitotic cells were subsequently arrested in G(1) but maintained normal elongated morphology and were viable for at least 21 days. We conclude that in SMC PTX causes post-mitotic cell cycle arrest rather than cell death.
Insights
Paclitaxel (PTX) causes cell cycle arrest in human arterial smooth muscle cells (SMCs), leading to multinucleated cells. Importantly, PTX does not induce apoptosis in SMCs, indicating cell cycle arrest rather than cell death.
Area of Science:
- Cell Biology
- Pharmacology
- Cardiovascular Research
Background:
- Paclitaxel (PTX) is a microtubule-active drug known to induce apoptosis in cancer cells.
- The effects of PTX on non-cancerous cells, such as smooth muscle cells, are less understood.
Purpose of the Study:
- To investigate the impact of Paclitaxel (PTX) on human arterial smooth muscle cells (SMCs).
- To determine if PTX induces apoptosis or cell cycle arrest in SMCs.
Main Methods:
- Exposure of human arterial SMCs to varying concentrations of PTX.
- Cell cycle analysis (G1, G2/M phases) and DNA content measurement.
- Assessment of apoptosis markers and cell viability over time.
Main Results:
- PTX induced both primary G1 arrest and post-mitotic G1 arrest in SMCs.
- Higher PTX concentrations (>12 ng/ml) resulted in multinucleated (MN) cells with 4C DNA content due to failed cytokinesis.
- Lower PTX concentrations (1-12 ng/ml) led to MN cells with 2C DNA content or G1 arrest without multinucleation.
- Crucially, PTX did not induce apoptosis in SMCs, with cells remaining viable and maintaining morphology.
Conclusions:
- Paclitaxel (PTX) treatment leads to post-mitotic cell cycle arrest in human arterial smooth muscle cells (SMCs).
- SMCs exit mitosis and arrest in G1, forming viable multinucleated cells, rather than undergoing apoptosis.
- These findings highlight a differential response of SMCs to PTX compared to typical cancer cell responses.
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