Blocking NF-κB nuclear translocation leads to p53-related autophagy activation and cell apoptosis

Bao-Song Zhu1, Chun-Gen Xing, Fang Lin

  • 1Department of General Surgery, The Second Affiliated Hospital, Soochow University, Suzhou, Jiangsu Province, China.

Abstract

Insights

Nuclear factor-κB (NF-κB) inhibitor SN50 demonstrated anti-tumor effects on gastric cancer cells by inducing apoptosis and autophagy. This cell death was dependent on p53-mediated activation of autophagy, highlighting a novel therapeutic pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Gastric carcinoma is a significant global health concern.
  • Nuclear factor-κB (NF-κB) signaling pathways are implicated in cancer progression.
  • Targeting NF-κB offers a potential therapeutic strategy for gastric cancer.

Purpose of the Study:

  • To investigate the anti-tumor effects of the NF-κB inhibitor SN50 in SGC7901 human gastric carcinoma cells.
  • To elucidate the underlying mechanisms, including apoptosis and autophagy.
  • To determine the role of p53 in SN50-induced anti-cancer activity.

Main Methods:

  • Cytotoxicity was assessed using MTT assays.
  • Apoptosis was detected via Hoechst 33258 staining.
  • Autophagy activation was monitored using monodansylcadaverine (MDC) and LC3 immunofluorescence.
  • Mitochondrial membrane potential was measured using JC-1.
  • Protein expression (p53, PUMA, DRAM, LC3, Beclin 1) was analyzed by Western blotting.
  • The role of p53 was investigated using the inhibitor pifithrin-α.

Main Results:

  • SN50 significantly inhibited SGC7901 cell viability.
  • SN50 treatment induced apoptosis and autophagy, evidenced by increased p53, PUMA, DRAM, LC3, and Beclin 1 expression.
  • Morphological changes indicated increased apoptosis and autophagosome formation.
  • Mitochondrial membrane potential collapse was observed.
  • p53 inhibition by pifithrin-α blocked SN50-induced autophagy and cell death.

Conclusions:

  • SN50 exhibits potent anti-tumor activity against gastric cancer cells.
  • The anti-tumor effects are mediated through the induction of p53-dependent apoptosis and autophagy.
  • Targeting NF-κB with SN50 represents a promising therapeutic approach for gastric carcinoma.

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