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Sulforaphane downregulates mitochondrial TIGAR via inhibiting mitochondrial transmembrane assembly and LONP1/CASP3

Dongxue Wu1, Sitian Zhang2, Yaheng Wu3

  • 1Neonatal Intensive Care Unit, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China.

Biochemical and Biophysical Research Communications
|March 29, 2025
PubMed

Insights

Sulforaphane (SFN) targets TP53-induced glycolysis and apoptosis regulator (TIGAR) in non-small cell lung cancer (NSCLC). SFN disrupts TIGAR

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • TP53-induced glycolysis and apoptosis regulator (TIGAR) is upregulated in non-small cell lung cancer (NSCLC).
  • High TIGAR expression correlates with poor prognosis and higher pathological grading in NSCLC patients.
  • The precise mechanism by which sulforaphane (SFN) affects TIGAR in NSCLC remains unclear.

Purpose of the Study:

  • To elucidate the mechanism of SFN's action on TIGAR in NSCLC.
  • To investigate SFN's impact on TIGAR localization and function within NSCLC cells.
  • To explore the potential of targeting TIGAR for anti-NSCLC therapy.

Main Methods:

  • Western blot analysis of cytosolic and mitochondrial fractions.
  • Immunoprecipitation to assess protein interactions.
  • Analysis of reactive oxygen species (ROS) and apoptosis markers.

Main Results:

  • SFN downregulates TIGAR, α-tubulin, Timm23, and Timm17A.
  • SFN disrupts microtubule-mediated mitochondrial import of TIGAR by reducing α-tubulin interactions.
  • SFN downregulates LONP1, leading to TIGAR cleavage, decreased NADPH, elevated ROS, and apoptosis.

Conclusions:

  • SFN inhibits NSCLC progression by targeting TIGAR.
  • Disruption of TIGAR's mitochondrial import and subsequent cleavage are key mechanisms.
  • Targeting TIGAR and its related pathways presents a promising therapeutic strategy for NSCLC.
Keywords:
ApoptosisLONP1MicrotubuleTIGARTimm23

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