Abstract
pks+ Escherichia coli (E. coli) triggers genomic instability in normal colon cells which leads to colorectal cancer (CRC) tumorigenesis. Previously, we reported a significant presentation of pks+ E. coli strains in CRC patients’ biopsies as compared to healthy cohorts. In this work, using an in vitro infection model, we further explored the ability of these strains in modulating cell cycle arrest and activation of apoptotic mediators in both primary colon epithelial cells (PCE) and CRC cells (HCT-116). Sixteen strains, of which eight tumours and the matching non-malignant tissues, respectively, from eight pks+ E. coli CRC patients were subjected to BrDU staining and cell cycle analysis via flow cytometry, while a subset of these strains underwent analysis of apoptotic mediators including caspase proteins, cellular reactive oxygen species (cROS) and mitochondrial membrane potential (MMP) via spectrophotometry as well as proinflammatory cytokines via flow cytometry. Data revealed that all strains exerted S-phase cell cycle blockade in both cells and G2/M phase in PCE cells only. Moreover, more significant upregulation of Caspase 9, cROS, proinflammatory cytokines and prominent downregulation of MMP were detected in HCT-116 cells indicating the potential role of pks related bacterial toxin as anticancer agent as compared to PCE cells which undergo cellular senescence leading to cell death without apparent upregulation of apoptotic mediators. These findings suggest the existence of discrepancies underlying the mechanism of action of pks+ E. coli on both cancer and normal cell lines. This work propounds the rationale to further understand the mechanism underlying pks+ E. coli-mediated CRC tumorigenesis and cancer killing.
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Data availability
The datasets generated during the current study will be available from the corresponding author on reasonable request.” The data will be deposited at Open Science Framework.
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Acknowledgements
We thank the surgeons from Universiti Malaya Medical Centre (UMMC), other medical staffs and research assistant involved in recruiting the patients.
Funding
This work was funded by: 1) University of Malaya Research Grant (RP016B-13HTM) and Ministry of Higher Education (MOHE), Malaysia under the High Impact Research (HIR)-MOHE Grant UM.C/625/1/HIR/MoE/CHAN/02 (H-50001-A000013) - Received by JV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Conceptualization, BM, KVV, VM, and JV: Methodology, BM, AKZ, TI, VM, KMV and JV: Validation, BM, TI and KMV: Formal analysis, BM: Resources, JV: writing—original draft preparation, AKZ, TI and BM: Writing—review and editing, AKZ, TI, BM, VM, JV, CTSJ and KMV. All authors have read and agreed to the published version of the manuscript.
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Zulpa, A.K., Barathan, M., Iyadorai, T. et al. Selective pks+ Escherichia coli strains induce cell cycle arrest and apoptosis in colon cancer cell line. World J Microbiol Biotechnol 39, 333 (2023). https://doi.org/10.1007/s11274-023-03767-1
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DOI: https://doi.org/10.1007/s11274-023-03767-1