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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)3565-3574
Number of pages10
JournalOncology Reports
Volume41
Issue number6
DOIs
Publication statusPublished - 2019 Jun 1

Fingerprint

Leydig Cell Tumor
Propofol
Caspases
Mitogen-Activated Protein Kinases
Apoptosis
Testicular Neoplasms
Aminobutyrates
Western World
Endoplasmic Reticulum Stress
Mitogen-Activated Protein Kinase 3
Poly(ADP-ribose) Polymerases
Caspase 9
Caspase 8
Leydig Cells
Propidium
JNK Mitogen-Activated Protein Kinases
Annexin A5
Mitogen-Activated Protein Kinase 1
G1 Phase
Hypnotics and Sedatives

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kang, Fu Chi ; Wang, Shu Chun ; So, Edmund Cheung ; Chang, Ming Min ; Wong, Kar Lok ; Cheng, Ka Shun ; Chen, Yung Chia ; Huang, Bu-Miin. / Propofol may increase caspase and MAPK pathways, and suppress the Akt pathway to induce apoptosis in MA‑10 mouse Leydig tumor cells. In: Oncology Reports. 2019 ; Vol. 41, No. 6. pp. 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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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.

In: Oncology Reports, Vol. 41, No. 6, 01.06.2019, p. 3565-3574.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Propofol may increase caspase and MAPK pathways, and suppress the Akt pathway to induce apoptosis in MA‑10 mouse Leydig tumor cells

AU - Kang, Fu Chi

AU - Wang, Shu Chun

AU - So, Edmund Cheung

AU - Chang, Ming Min

AU - Wong, Kar Lok

AU - Cheng, Ka Shun

AU - Chen, Yung Chia

AU - Huang, Bu-Miin

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AB - 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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