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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.
Objective:
The aim of this study was to investigate the effects of CaM antagonist, PTZ, and TFP on cell proliferation and migration of colon cancer cells and its impact on POPDC protein expression.
Methods:
The 50% inhibitory concentration (IC50) of PTZ and TFP in SW1116, SW480, HCT-15, and COLO205 colon cancer cell lines are measured using MTT. Western blot and immunocytochemistry were used to determine the expression of PCNA, cyclin D1 (CD1), and POPDC proteins. Cell migration was observed using a scratch wound-healing assay.
Results:
Treatment with PTZ and TFP inhibited colon cancer cells growth in a dose-dependent manner. PTZ and TFP significantly inhibited the activation of proliferation markers, PCNA and CD1, and the migration of colon cancer cells. Furthermore, POPDC protein was significantly suppressed in all cell types of colon cancer, particularly in SW480. Finally, the CaM antagonist upregulates the POPDC1 expression in colon cancer cells.
Conclusion:
These findings suggest that CaM antagonists suppress colon cancer cells proliferation via downregulation of CD1 and PCNA. In addition, POPDC protein could be used as a biomarker in colon cancer, and CaM antagonist could be used to regulate POPDC1 expression. This study suggests that targeting POPDC1 with CaM inhibition could be a potential therapeutic strategy for colon cancer treatment.
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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.
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