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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
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Trichostatin A promotes GLI1 degradation and P21 expression in multiple myeloma cells

Yan Geng1, Jing Liu2, Ying Xie2

  • 1Department of Clinical Laboratory, Shanxi Provincial People's Hospital, Taiyuan, Shanxi, 030012 China.

Cancer Management and Research
|September 15, 2018
PubMed
Abstract

Insights

Trichostatin A (TSA) effectively inhibits multiple myeloma (MM) cell growth and induces apoptosis by suppressing hedgehog signaling. This histone deacetylase inhibitor shows promise for MM cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Histone deacetylase inhibitors (HDACi) are promising cancer therapeutics.
  • Trichostatin A (TSA), an HDACi, demonstrates antitumor effects in various cancers.
  • The precise mechanisms of TSA in multiple myeloma (MM) require further investigation.

Purpose of the Study:

  • To investigate the effects of TSA on multiple myeloma (MM) cell lines.
  • To elucidate the underlying molecular mechanisms of TSA-induced cytotoxicity in MM.
  • To evaluate the role of hedgehog signaling in TSA's anti-MM activity.

Main Methods:

  • Cell proliferation, cell cycle, and survival assays were performed on MM cells treated with TSA.
  • Immunofluorescence, immunoprecipitation, western blots, and qPCR were used to analyze GLI1 protein and p21.
  • Proteasome-dependent degradation and mRNA transcription were assessed.

Main Results:

  • TSA exhibited time- and dose-dependent cytotoxicity, suppressed proliferation, and induced p21 upregulation while decreasing cyclin D1 in MM cells.
  • TSA downregulated GLI1, inhibited its nuclear accumulation, and weakened MYC and SURVIVIN expression, indicating hedgehog pathway inhibition.
  • TSA accelerated GLI1 degradation via the proteasome and p21 induction contributed to GLI1 downregulation; exogenous GLI1 expression rescued TSA-induced apoptosis.

Conclusions:

  • TSA effectively represses multiple myeloma cell growth and induces apoptosis.
  • Inhibition of the hedgehog signaling pathway is a key mechanism underlying TSA's cytotoxic effects in MM.
  • TSA represents a potential therapeutic agent for multiple myeloma.
Keywords:
hedgehog signalinghistone deacetylasemultiple myelomatrichostatin A

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