Chelerythrine Chloride Downregulates β-Catenin and Inhibits Stem Cell Properties of Non-Small Cell Lung Carcinoma.

Win Sen Heng,Shiau-Chuen Cheah

doi:10.3390/molecules25010224

Abstract

Plant secondary metabolites have been seen as alternatives to seeking new medicines for treating various diseases. Phytochemical scientists remain hopeful that compounds isolated from natural sources could help alleviate the leading problem in oncology—the lung malignancy that kills an estimated two million people annually. In the present study, we characterized a medicinal compound benzophenanthridine alkaloid, called chelerythrine chloride for its anti-tumorigenic activities. Cell viability assays confirmed its cytotoxicity and anti-proliferative activity in non-small cell lung carcinoma (NSCLC) cell lines. Immunofluorescence staining of β-catenin revealed that there was a reduction of nuclear content as well as overall cellular content of β-catenin after treating NCI-H1703 with chelerythrine chloride. In functional characterizations, we observed favorable inhibitory activities of chelerythrine chloride in cancer stem cell (CSC) properties, which include soft agar colony-forming, migration, invasion, and spheroid forming abilities. Interesting observations in chelerythrine chloride treatment noted that its action abides to certain concentration-specific-targeting behavior in modulating β-catenin expression and apoptotic cell death. The downregulation of β-catenin implicates the downregulation of CSC transcription factors like SOX2 and MYC. In conclusion, chelerythrine chloride has the potential to mitigate cancer growth due to inhibitory actions toward the tumorigenic activity of CSC in lung cancer and it can be flexibly adjusted according to concentration to modulate specific targeting in different cell lines.

Highlights

In the 21st century, we still very much rely on the testing of phytochemical compounds to facilitate drug discovery
Our findings suggested that chelerythrine chloride possessed some inhibitory activity toward the Wnt/β-catenin pathway through β-catenin downregulation
Our findings suggested that chelerythrine chloride possessed some inhibitory activity toward the Wnt/β‐catenin pathway through β‐catenin downregulation

Summary

Introduction

In the 21st century, we still very much rely on the testing of phytochemical compounds to facilitate drug discovery. It is not surprising that the wonder drug hailed by Paul Ehrlich as a “magic bullet”. Growing interest sparks on plant-derived compounds because of their medicinally valuable bioactivities [1,2]. Plant products have been used in various aspects of life, most importantly for our daily needs that directly contribute to our well-being. Besides fulfilling our needs in foods and beverages, plant products have historically been used for herbs and remedies for various ailments. Phytochemical compounds are known as plant secondary metabolites. They are plants’ secondary needs that are not involved in their primary metabolism

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Conclusion