Curcumin induces apoptotic cell death via Oct4 inhibition and GSK-3β activation in NCCIT cells

Ji Ho Yun1,2, Young Gyun Park1,3, Kyung-Mi Lee1

  • 1Natural Products Research Center, KIST Gangneung Institute, Gangneung, Gangwon-do, Korea.

Abstract

Insights

Curcumin (CUR) inhibits Octamer-binding transcription factor 4 (Oct4) in cancer cells, promoting apoptosis and potentially enhancing cancer prevention and chemoresistance by targeting cancer stem cells (CSCs).

Area of Science:

  • Cancer Biology
  • Stem Cell Research
  • Pharmacology

Background:

  • Octamer-binding transcription factor 4 (Oct4) is crucial for embryonic stem cell maintenance.
  • Oct4 is also found in cancer stem cells (CSCs), correlating with tumor progression and chemoresistance.
  • Curcumin (CUR) is a known cancer chemopreventive agent.

Purpose of the Study:

  • To investigate if CUR induces apoptotic cell death by inhibiting Oct4 levels in NCCIT human embryonic carcinoma cells.
  • To elucidate the molecular mechanisms underlying CUR's effects on Oct4 and apoptosis.
  • To explore the potential of CUR as a therapeutic agent against CSCs.

Main Methods:

  • Dual luciferase assays to measure Oct4 transcription levels.
  • Quantitative analysis of Oct4 mRNA and protein expression.
  • Apoptosis assays (subG0/G1 content, caspase cleavage) and loss-of-function experiments (Oct4 siRNA).
  • Western blot analysis for glycogen synthase kinase 3 beta (GSK-3β) levels and evaluation using GSK-3β inhibitors.

Main Results:

  • CUR significantly inhibited Oct4 transcription, mRNA, and protein levels in a dose-dependent manner.
  • CUR treatment increased apoptotic cell death, including caspase activation and pro-apoptotic protein expression.
  • CUR induced GSK-3β activation, contributing to increased apoptotic cell death.

Conclusions:

  • CUR induces apoptotic cell death in cancer cells by inhibiting Oct4 and activating GSK-3β.
  • CUR demonstrates potential as a cancer chemopreventive agent by suppressing tumor progression and enhancing chemoresistance.
  • Eliminating CSCs through CUR treatment may offer a strategy to combat cancer recurrence and improve treatment outcomes.

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