Novel Midkine Inhibitor Induces Cell Cycle Arrest and Apoptosis in Multiple Myeloma

Kodcharat Cheevapruk1,2,3, Mikinori Ueno1,4, Prin Sungwan1,2

  • 1Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.

Anticancer Research
|February 29, 2024
PubMed
Abstract

Insights

The novel midkine inhibitor, iMDK, effectively reduces multiple myeloma (MM) cell proliferation by inducing cell cycle arrest and apoptosis. This compound shows promise as a potential new treatment for this hematological malignancy.

Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Multiple myeloma (MM) is a prevalent hematological malignancy with limited curative treatment options.
  • Novel therapeutic strategies are crucial for improving outcomes in MM patients.

Purpose of the Study:

  • To investigate the anti-cancer effects of the midkine inhibitor, iMDK, on multiple myeloma cell lines.
  • To elucidate the molecular mechanisms underlying iMDK's anti-myeloma activity.

Main Methods:

  • Antiproliferative activity was assessed using the MTT assay.
  • Cell cycle progression and apoptosis were analyzed via flow cytometry.
  • Western blotting was employed to examine key cell cycle and apoptosis regulatory proteins.

Main Results:

  • iMDK demonstrated dose- and time-dependent inhibition of MM cell proliferation.
  • Treatment with iMDK induced G2/M phase cell cycle arrest, linked to reduced Cdc20 expression.
  • iMDK triggered apoptosis by down-regulating anti-apoptotic proteins (Bcl-2, Bcl-xL, Mcl-1, c-FLIP) and activating intrinsic and extrinsic apoptotic pathways.

Conclusions:

  • The midkine inhibitor iMDK exhibits significant anti-myeloma activity.
  • iMDK represents a potential therapeutic candidate for the treatment of multiple myeloma.

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