Parthenolide-induced apoptosis in multiple myeloma cells involves reactive oxygen species generation and cell

Wei Wang1, Masaaki Adachi, Rina Kawamura

  • 1Division of Molecular Oncology and Molecular Diagnosis, Graduate School of Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-Ku, Sapporo, 060-8543, Japan.

Insights

Parthenolide (PTL) induces cancer cell death through oxidative stress. Intracellular catalase levels determine multiple myeloma cell sensitivity to PTL, offering a potential therapeutic target.

Area of Science:

  • Biochemistry
  • Oncology
  • Cell Biology

Background:

  • Parthenolide (PTL), a sesquiterpene lactone, exhibits potent anticancer properties.
  • Multiple myeloma (MM) is a cancer of plasma cells, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To investigate the mechanism of PTL-induced apoptosis in multiple myeloma cells.
  • To identify factors influencing differential sensitivity of MM cells to PTL.

Main Methods:

  • Treatment of MM cell lines and primary MM cells with PTL.
  • Assessment of apoptosis, reactive oxygen species (ROS) generation, and catalase activity.
  • Inhibition of ROS with L-N-acetylcysteine (L-NAC) and catalase inhibition/knockdown.

Main Results:

  • PTL induced apoptosis in MM cells, correlating with increased ROS generation.
  • Normal lymphocytes were less sensitive to PTL compared to MM cells.
  • Lower catalase activity in sensitive MM cell lines (KMM-1, MM1S) compared to less sensitive ones (KMS-5, NCI-H929) and normal lymphocytes.
  • Catalase inhibition or knockdown sensitized MM cells to PTL-induced cell death.

Conclusions:

  • PTL-induced apoptosis in MM cells is mediated by ROS.
  • Intracellular catalase activity is a key determinant of MM cell sensitivity to PTL.
  • Targeting catalase may enhance the efficacy of PTL in multiple myeloma treatment.

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