Casticin Attenuates Stemness in Cervical Cancer Stem-Like Cells by Regulating Activity and Expression of DNMT1

Xue-Li Wang1, Xiao-Zheng Cao2,3, Dao-Yuan Wang4,5

  • 1Medical College, Hunan University of Medicine, Huaihua, Hunan Province, 418000, China.

Abstract

Insights

Casticin (CAS) effectively suppresses cancer stem-like cell (CSLC) stemness in cervical cancer by inhibiting DNA methyltransferase 1 (DNMT1) activation. This suggests CAS is a promising candidate for cervical cancer prevention and therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Stem Cell Research

Background:

  • Cancer stem-like cells (CSLCs) drive tumor growth and recurrence in cervical cancer.
  • DNA methyltransferase 1 (DNMT1) is implicated in maintaining stemness and cancer progression.
  • Understanding mechanisms to target CSLCs is crucial for effective cervical cancer treatment.

Purpose of the Study:

  • To investigate the effect of casticin (CAS) on the stemness of human cervical cancer stem-like cells (CCSLCs).
  • To elucidate the underlying molecular mechanism involving DNA methyltransferase 1 (DNMT1).

Main Methods:

  • CCSLCs were derived from HeLa and CaSki cells.
  • DNMT1 activity, mRNA levels, and stemness markers (Nanog, Sox2, CD133, CD44) were assessed.
  • DNMT1 knockdown and overexpression were performed to study CAS mechanism of action.

Main Results:

  • DNMT1 activity was elevated in CCSLCs.
  • DNMT1 knockdown reduced stemness and proliferation in CCSLCs, while overexpression had the opposite effect.
  • CAS significantly inhibited DNMT1 activity, transcription, and stemness in CCSLCs, with enhanced effects upon DNMT1 knockdown.

Conclusions:

  • Casticin (CAS) inhibits stemness in cervical cancer stem-like cells (CCSLCs) by suppressing DNMT1 activation.
  • CAS demonstrates potential as a preventive and therapeutic agent for cervical cancer.
  • Targeting DNMT1 is a viable strategy for controlling CSLC-driven cervical cancer.

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