CTPS cytoophidia formation affects cell cycle progression and promotes TSN‑induced apoptosis of MKN45 cells

Fu,Xuepeng; Chen,Wen; Pan,Yang; Liu,Chang; Zhang,Zhenzhu; Shao,Shuli; Zhang,Weiwei

doi:10.3892/mmr.2022.12835

CTPS cytoophidia formation affects cell cycle progression and promotes TSN‑induced apoptosis of MKN45 cells

Authors:
- Xuepeng Fu
- Wen Chen
- Yang Pan
- Chang Liu
- Zhenzhu Zhang
- Shuli Shao
- Weiwei Zhang
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Affiliations: Department of Life Science and Agroforestry, Qiqihar University, Qiqihar, Heilongjiang 161006, P.R. China
Published online on: August 29, 2022 https://doi.org/10.3892/mmr.2022.12835
Article Number: 319
Copyright: © Fu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cytidine triphosphate synthase (CTPS) forms filamentous structures termed cytoophidia in numerous types of cell. Toosendanin (TSN) is a tetracyclic triterpenoid and induces CTPS to form cytoophidia in MKN45 cells. However, the effects of CTPS cytoophidia on the proliferation and apoptosis of human gastric cancer cells remain poorly understood. In the present study, CTPS‑overexpression and R294D‑CTPS mutant vectors were generated to assess the effect of CTPS cytoophidia on the proliferation and apoptosis of gastric cancer MKN45 cells. Formation of CTPS cytoophidia significantly inhibited MKN45 cell proliferation (evaluated using EdU incorporation assay), significantly blocked the cell cycle in G₁ phase (assessed using flow cytometry) and significantly decreased mRNA and protein expression levels of cyclin D1 (assessed by reverse transcription‑quantitative PCR and western blotting, respectively). Furthermore, the number of apoptotic bodies and apoptosis rate were markedly elevated and mitochondrial membrane potential was markedly decreased. Moreover, mRNA and protein expression levels of Bax increased and Bcl‑2 decreased markedly in MKN45 cells following transfection with the CTPS‑overexpression vector. The proliferation rate increased, percentage of G₁/G₀‑phase cells decreased and apoptosis was attenuated in cells transfected with the R294D‑CTPS mutant vector and this mutation did not lead to formation of cytoophidia. The results of the present study suggested that formation of CTPS cytoophidia inhibited proliferation and promoted apoptosis in MKN45 cells. These results may provide insights into the role of CTPS cytoophidia in cancer cell proliferation and apoptosis.

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