Modulation of POPDC1 Expression by Phenothiazine and Trifluoperazine Suppress Colon Cancer Growth and Migration

Fiona Macniesia Thomas1, Suhaini Sudi1, Falah Abas Muhamad Salih1,2

  • 1Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu 88400, Sabah, Malaysia.

Abstract

Insights

Calmodulin (CaM) antagonists, like PTZ and TFP, inhibit colon cancer cell proliferation and migration by downregulating PCNA and CD1. POPDC protein shows potential as a colon cancer biomarker, with CaM inhibition regulating POPDC1 expression for therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Colon cancer remains a significant global health challenge.
  • Calmodulin (CaM) plays a crucial role in various cellular processes, including proliferation and migration.
  • Understanding molecular targets for colon cancer therapy is essential.

Purpose of the Study:

  • To investigate the effects of CaM antagonists (PTZ, TFP) on colon cancer cell proliferation and migration.
  • To assess the impact of CaM antagonists on POPDC protein expression in colon cancer cells.
  • To explore the therapeutic potential of targeting CaM and POPDC1 in colon cancer.

Main Methods:

  • Utilized MTT assays to determine the 50% inhibitory concentration (IC50) of PTZ and TFP in multiple colon cancer cell lines.
  • Employed Western blot and immunocytochemistry to analyze the expression of proliferation markers (PCNA, CD1) and POPDC proteins.
  • Assessed cell migration using scratch wound-healing assays.

Main Results:

  • PTZ and TFP demonstrated dose-dependent inhibition of colon cancer cell growth.
  • Significant suppression of proliferation markers (PCNA, CD1) and cell migration was observed.
  • POPDC protein expression was notably reduced in all tested colon cancer cell lines, particularly SW480.
  • CaM antagonists were found to upregulate POPDC1 expression.

Conclusions:

  • CaM antagonists effectively suppress colon cancer cell proliferation by downregulating CD1 and PCNA.
  • POPDC protein emerges as a potential biomarker for colon cancer.
  • CaM antagonists can modulate POPDC1 expression, suggesting a therapeutic avenue.
  • Targeting POPDC1 via CaM inhibition presents a promising strategy for colon cancer treatment.