Propofol may increase caspase and MAPK pathways, and suppress the Akt pathway to induce apoptosis in MA‑10 mouse Leydig tumor cells

Kang,Fu‑Chi; Wang,Shu‑Chun; So,Edmund   Cheung; Chang,Ming‑Min; Wong,Kar‑Lok; Cheng,Ka  Shun; Chen,Yung‑Chia; Huang,Bu‑Miin

doi:10.3892/or.2019.7129

Propofol may increase caspase and MAPK pathways, and suppress the Akt pathway to induce apoptosis in MA‑10 mouse Leydig tumor cells

Authors:
- Fu‑Chi Kang
- Shu‑Chun Wang
- Edmund Cheung So
- Ming‑Min Chang
- Kar‑Lok Wong
- Ka Shun Cheng
- Yung‑Chia Chen
- Bu‑Miin Huang
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Affiliations: Department of Anesthesia, Chi Mei Medical Center, Chiali, Tainan 70722, R.O.C., Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan 70101, R.O.C., Department of Anesthesia, China Medical University, Taichung 40406, R.O.C., Department of Anatomy, School of Medicine, Kaohsiung Medical University, Kaohsiung 80807, R.O.C.
Published online on: April 18, 2019 https://doi.org/10.3892/or.2019.7129
Pages: 3565-3574

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Abstract

In the western world, there is an increasing trend of occurrence in testicular cancer. Treatment of malignant testicular cancer is primarily combined surgery with various chemical drugs. Propofol has been frequently used as an anesthetic and sedative induction agent, which could modulate different γ‑aminobutyric acid receptors in the central nervous system. Studies demonstrated that propofol activates endoplasmic reticulum stress to induce apoptosis in lung cancer. However, it remains elusive whether propofol regulates caspase and/or mitogen‑activated protein kinase (MAPK) pathways to induce apoptosis in Leydig tumor cells. In the present study, MA‑10 mouse Leydig tumor cells were treated with propofol, and possible signal pathways associated with apoptosis were investigated. Results demonstrated that increasing dosage of propofol (300‑600 µM) for 24 h significantly decreased cell viability in MA‑10 cells (P<0.05). In flow cytometry analysis, the amount of sub‑G1 phase cell numbers in MA‑10 cells was significantly increased by propofol (P<0.05). Additionally, Annexin V/propidium iodide double staining further confirmed that propofol could induce MA‑10 cell apoptosis. Furthermore, cleaved caspase‑8, ‑9 and ‑3, and/or poly(ADP‑ribose) polymerase were significantly activated following treatment of propofol in MA‑10 cells. In addition, c‑Jun N‑terminal kinase, extracellular signal‑regulated kinase 1/2, and p38 were significantly activated by propofol in MA‑10 cells (P<0.05), indicating that propofol may induce apoptosis through the MAPK pathway. Additionally, propofol diminished the phosphorylation of Akt to activate apoptosis in MA‑10 cells. In conclusion, propofol may induce MA‑10 cell apoptosis by activating caspase and MAPK pathways, and inhibiting the Akt pathway in MA‑10 cells, demonstrating that propofol may be a potential anticancer agent against Leydig cell cancer.

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