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CDKN1A Gene Expression in Two Multiple Myeloma Cell Lines With Different P53 Functionality

Denisa Hrckova Drozdkova1,2, Jan Gursky3, Jiri Minarik4,5

  • 1Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic denisa.drozdkova@seznam.cz katerina.smesny@upol.cz.

Anticancer Research
|September 4, 2020
PubMed
Abstract

Insights

Suberoylanilide hydroxamic acid (SAHA) shows potential as an anticancer drug for multiple myeloma. It effectively targets cancer cells regardless of their TP53 status, indicating broad applicability.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Multiple myeloma is a complex plasma cell cancer.
  • Histone deacetylase (HDAC) inhibitors are promising cancer treatments.
  • The exact mechanisms of HDAC inhibitors are not fully understood.

Purpose of the Study:

  • To investigate the effects of HDAC inhibitors on multiple myeloma cells.
  • To analyze cell-cycle regulation and apoptosis induced by SAHA and SBHA.
  • To explore the role of TP53 status in the response to HDAC inhibitors.

Main Methods:

  • Utilized multiple myeloma cell lines (RPMI8226 and U266) with different TP53 statuses.
  • Administered two HDAC inhibitors: suberohydroxamic acid (SAHA) and suberoylanilide hydroxamic acid (SBHA).
  • Performed gene-expression analysis to assess cellular responses.

Main Results:

  • SAHA treatment upregulated CDKN1A/p21 in TP53-deleted U266 cells, suggesting P53-independent activation.
  • Both SAHA and SBHA significantly increased CDKN1A gene expression in TP53-mutated RPMI8226 cells.
  • HDAC inhibitors demonstrate differential effects based on TP53 genetic status.

Conclusions:

  • SAHA exhibits potential as a pro-apoptotic and anticancer agent for multiple myeloma.
  • SAHA may be effective across diverse multiple myeloma patient populations.
  • Further research into HDAC inhibitors' mechanisms is warranted.
Keywords:
Multiple myelomaapoptosisgene expressionmyeloma cell lines

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