Glaucocalyxin B Attenuates Ovarian Cancer Cell Growth and Cisplatin Resistance In Vitro via Activating Oxidative Stress

Oxid Med Cell Longev. 2022 Feb 25:2022:6324292. doi: 10.1155/2022/6324292. eCollection 2022.

Abstract

Ovarian cancer is one of the fatal gynecological cancers around the world. Cisplatin is the first-line chemotherapy drug for the clinical treatment of ovarian cancer. However, many patients with ovarian cancer are still suffering from resistance to cisplatin. Therefore, the new drug combinations or treatment strategies for ovarian cancer are urgently needed. Glaucocalyxin B (GLB), a diterpenoid isolated from the aerial parts of Rabdosia japonica, has shown antitumor activity in some tumors. However, the mechanisms by which GLB inhibits ovarian cancer remain unclear. In the present study, we showed that GLB potently inhibits ovarian cancer cell growth in a dose-dependent manner. Furthermore, we found that GLB has a notably synergistic antitumor effect with cisplatin. Mechanistically, we found that GLB enhances the sensitivity of ovarian cancer cells to cisplatin via increasing reactive oxygen species (ROS) levels, the phosphorylation of c-Jun N-terminal kinase (JNK), and DNA damage. Interestingly, a synergistic inhibitory effect of GLB with cisplatin was also observed in the cells which were resistance to cisplatin. Together, these data suggest that GLB can sensitize ovarian cancer cells to cisplatin by increasing ROS levels.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cisplatin / pharmacology*
  • DNA Damage / drug effects
  • Diterpenes, Kaurane / pharmacology*
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Synergism
  • Female
  • Humans
  • Isodon / chemistry*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Signaling System / drug effects*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Oxidative Stress / drug effects*
  • Phytochemicals / pharmacology*
  • Plant Extracts / pharmacology*
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents
  • Diterpenes, Kaurane
  • Phytochemicals
  • Plant Extracts
  • Reactive Oxygen Species
  • glaucocalyxin B
  • JNK Mitogen-Activated Protein Kinases
  • Cisplatin