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Coix seed oil regulates mitochondrial functional damage to induce apoptosis of human pancreatic cancer cells via the PTEN/PI3K/AKT signaling pathway

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Abstract

Background

Coix seed oil (CSO) has a wide range of anticancer effects. However, the mechanism of action against pancreatic cancer (PC) and regulation of mitochondria in vitro is still unclear.

Materials and results

This research investigated the possible mechanism of CSO induction of PC cell apoptosis and regulating mitochondrial functional damage. Proliferation of PC cells, mitochondrial membrane potential (MMP), qualitative and quantitative analysis of PC cell apoptosis, openness of mitochondrial permeability transition pore, related protein expression, generation of reactive oxygen species (ROS), and gene expression were determined by cell counting kit-8, JC-1 staining, acridine orange and ethidium bromide staining, flow cytometry, calcein-AM/cobalt staining, western blotting, dichlorofluorescein diacetate probe, and quantitative real-time reverse transcription-polymerase chain reaction, respectively. We confirmed that PTEN protein was involved in CSO-induced PANC-1 cell apoptosis and mitochondrial functional damage. CSO induced depolarization of MMP, increased opening of the mitochondrial permeability transition pore, increased ROS production, and further increased mitochondrial damage. Additionally, CSO downregulated expression of p-AKT and p-PI3K proteins; upregulated protein expression of cleaved caspase-9, Bax, cleaved caspase-3 and cytochrome c; and downregulated expression of Bcl-2 by upregulating the PTEN gene. The corresponding protein expression was consistent with the gene expression level. Furthermore, the loss of function of PTEN protein reduces the ability of CSO to induce apoptosis of PANC-1 cells and damage to mitochondrial function.

Conclusions

CSO induces apoptosis of PANC-1 PC cells by modulating mitochondrial functional impairment and related apoptotic molecules via PTEN, which may be closely related to the PI3K/AKT signaling pathway.

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Data Availability

All datasets for the analysis in the present study are available upon reasonable request to the corresponding author.

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Acknowledgements

This study was supported by Qiqihar Academy of Medical Sciences (Grant Number QMSI2019M-12), and thanks to the Third Affiliated Hospital of Qiqihar Medical University for funding this research.

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Authors and Affiliations

  1. Department of General Surgery, The First Affiliated Hospital, Jiamusi University, 154003, Jiamusi, Heilongjiang Province, China

    Jian Yang

  2. Department of Medical Oncology, The Third Affiliated Hospital, Qiqihar Medical University, 161099, Qiqihar, Heilongjiang Province, China

    Ying Liu

  3. Department of Ultrasound, The Third Affiliated Hospital, Qiqihar Medical University, 161099, Qiqihar, Heilongjiang Province, China

    Shengnan Lu

  4. Department of Radiology, The Third Affiliated Hospital, Qiqihar Medical University, 161099, Qiqihar, Heilongjiang Province, China

    Xuejia Sun

  5. Department of Science and Education, The Third Affiliated Hospital, Qiqihar Medical University, 161099, Qiqihar, Heilongjiang Province, China

    Yue Yin

  6. Department of Vascular surgery, The First Affiliated Hospital, Jiamusi University, 154003, Jiamusi, Heilongjiang Province, China

    Kaifeng Wang

  7. Central Laboratory, The Third Affiliated Hospital, Qiqihar Medical University, 27 Taishun Street, Tiefeng District, 161099, Qiqihar, Heilongjiang Province, China

    Shi Liu

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  1. Jian Yang
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Contributions

JY: conceptualization, methodology, software, validation, and writing—original draft preparation; YL: formal analysis and resources; S-NL: investigation and data curation; X-JS: software; YY: investigation and data curation; K-FW: conceptualization, formal analysis, and supervision; SL: project administration, funding application, and writing—review & editing and supervision; All authors reviewed the paper and approved the submitted version.

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Correspondence to Shi Liu.

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Yang, J., Liu, Y., Lu, S. et al. Coix seed oil regulates mitochondrial functional damage to induce apoptosis of human pancreatic cancer cells via the PTEN/PI3K/AKT signaling pathway. Mol Biol Rep 49, 5897–5909 (2022). https://doi.org/10.1007/s11033-022-07371-8

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