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Bullatine A suppresses glioma cell growth by targeting SIRT6

Zhi Wang1,2, Yushuai Zhu1,2, Can Luo1,2

  • 1Department of Cerebrovascular Disease, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570311, PR China.

Heliyon
|January 23, 2025
PubMed

Insights

Bullatine A (BLA) shows potential in treating malignant gliomas by inhibiting cancer cell proliferation and inducing apoptosis. This diterpenoid alkaloid targets SIRT6, offering a promising therapeutic avenue for brain tumors.

Area of Science:

  • Neuro-oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Gliomas are primary brain tumors with poor prognosis, necessitating novel therapeutic strategies.
  • Current treatments like chemotherapy offer limited efficacy for highly malignant gliomas.

Purpose of the Study:

  • To investigate the anti-glioma effects of Bullatine A (BLA).
  • To elucidate the molecular mechanisms underlying BLA's action in human glioblastoma cells.

Main Methods:

  • In vitro studies using U87MG and U251 glioblastoma cell lines.
  • Assessment of cell proliferation, survival, apoptosis, cell cycle, and protein expression.
  • Histone acetylation and SIRT6 activity analysis.
  • SIRT6 knockout experiments to confirm mechanism.

Main Results:

  • BLA inhibited glioblastoma cell proliferation and survival in a dose-dependent manner.
  • BLA induced apoptosis by modulating caspase and Bcl-2 family proteins.
  • BLA caused G2/M cell cycle arrest and affected ERK/Myc pathways.
  • BLA inhibited histone acetylation and upregulated SIRT6, with SIRT6 being crucial for its anti-glioma effects.

Conclusions:

  • BLA demonstrates significant anti-glioma activity by inhibiting proliferation and inducing apoptosis.
  • The therapeutic effects of BLA are mediated through the SIRT6 pathway.
  • BLA represents a potential novel therapeutic agent for glioma treatment.
Keywords:
ApoptosisBullatine aCell proliferationGliomaSIRT6

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