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HDACi induces apoptosis of osteosarcoma cells by inhibiting the MAPK pathway

Chao Qin1, Tao-Tao Lin1, Yi-Min Lin1

  • 1Department of orthopedics, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, P. R. China.

Scientific Reports
|January 30, 2026
PubMed

Insights

4-phenylbutyric acid (4-PA), a histone deacetylase inhibitor (HDACi), significantly inhibits osteosarcoma (OS) cell growth and induces apoptosis. This occurs by suppressing the MAPK/ERK pathway, offering a potential therapeutic strategy for OS.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Osteosarcoma (OS) is a primary bone malignancy with limited effective treatments.
  • Histone deacetylase inhibitors (HDACi) show potential anti-cancer properties.
  • Understanding the molecular mechanisms of HDACi in OS is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the anti-cancer effects of 4-phenylbutyric acid (4-PA), an HDACi, on osteosarcoma (OS) cells.
  • To elucidate the underlying molecular mechanisms, particularly the involvement of the MAPK/ERK pathway.
  • To evaluate the in vivo efficacy of 4-PA in an OS animal model.

Main Methods:

  • Cell viability, invasion, migration, and colony formation assays were performed.
  • Apoptosis and cell cycle progression were analyzed using flow cytometry.
  • mRNA sequencing and Western blotting were employed to study molecular changes.
  • In vivo experiments in animal models validated the findings.

Main Results:

  • 4-PA significantly inhibited OS cell proliferation, invasion, migration, and colony formation.
  • 4-PA induced significant apoptosis and cell cycle arrest in OS cells.
  • mRNA sequencing and Western blot revealed 4-PA suppresses the MAPK/ERK pathway.
  • In vivo studies confirmed 4-PA's inhibitory effect on OS tumor growth and its pro-apoptotic action.

Conclusions:

  • 4-PA effectively suppresses malignant biological behaviors of OS cells.
  • 4-PA induces apoptosis in OS cells, partly through the inhibition of the MAPK/ERK pathway.
  • HDACi, like 4-PA, represents a promising therapeutic avenue for osteosarcoma.
Keywords:
4-PAApoptosisHDACiMAPK/ERK signaling pathwayOsteosarcoma

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