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[Effect of Celastrol Based on IRAK4/ERK/p38 Signaling Pathway on Proliferation and Apoptosis of Multiple Myeloma

Xiao-Meng Xu1, Di Kang2, Xin-Yu Zhu1

  • 1Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine; Nanjing 210029, Jiangsu Province, China,First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China.

Zhongguo Shi Yan Xue Ye Xue Za Zhi
|February 6, 2022
PubMed
Abstract

Insights

Celastrol inhibits multiple myeloma cell growth and promotes apoptosis by affecting the IRAK4/ERK/p38 pathway. Combining celastrol with bortezomib shows a synergistic effect, enhancing anti-myeloma activity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Multiple myeloma (MM) is a hematological malignancy characterized by uncontrolled proliferation of plasma cells.
  • Investigating novel therapeutic agents and their mechanisms of action is crucial for improving MM treatment outcomes.

Purpose of the Study:

  • To evaluate the anti-proliferative and pro-apoptotic effects of celastrol on human multiple myeloma cell lines (H929 and ARP-1).
  • To elucidate the role of the IRAK4/ERK/p38 signaling pathway in celastrol-mediated effects.
  • To determine the synergistic potential of combining celastrol with bortezomib in MM treatment.

Main Methods:

  • Cell viability was assessed using the CCK-8 assay.
  • Apoptosis and necrosis rates were determined by Annexin V/PI staining.
  • Protein expression levels of key signaling molecules were analyzed via Western blot.

Main Results:

  • Celastrol significantly inhibited H929 and ARP-1 cell proliferation and induced apoptosis in a time-dependent manner.
  • Celastrol treatment led to increased PARP and cleaved caspase-3 expression, while decreasing phosphorylation of IRAK4, ERK, and p38.
  • The combination of celastrol and bortezomib demonstrated a synergistic effect, resulting in reduced cell survival and elevated apoptosis rates compared to monotherapy.

Conclusions:

  • Celastrol exhibits anti-myeloma activity by inhibiting cell proliferation and inducing apoptosis, potentially through the IRAK4/ERK/p38 signaling pathway.
  • The combination of celastrol and bortezomib offers a synergistic therapeutic strategy for multiple myeloma, enhancing efficacy in inhibiting cell growth and inducing apoptosis.
Keywords:
ARP-1H929IRAK4/ERK/p38 signaling pathwaybortezomibcelastrolmultiple myeloma

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