Combined Protein and Alkaloid Research of Chelidonium majus Latex Reveals CmMLP1 Accompanied by Alkaloids with Cytotoxic Potential to Human Cervical Carcinoma Cells.

Robert Nawrot,Katarzyna Magdalena Dolata,Anna Goździcka-Józefiak,Piotr Józef Rudzki,Oskar Musidlak,Elżbieta Urszula Stolarczyk,Alicja Warowicka,Jacek Musijowski

doi:10.3390/ijms222111838

Abstract

Chelidonium majus L. is a latex-bearing plant used in traditional folk medicine to treat human papillomavirus (HPV)-caused warts, papillae, and condylomas. Its latex and extracts are rich in many low-molecular compounds and proteins, but there is little or no information on their potential interaction. We describe the isolation and identification of a novel major latex protein (CmMLP1) composed of 147 amino acids and present a model of its structure containing a conserved hydrophobic cavity with high affinity to berberine, 8-hydroxycheleritrine, and dihydroberberine. CmMLP1 and the accompanying three alkaloids were present in the eluted chromatographic fractions of latex. They decreased in vitro viability of human cervical cancer cells (HPV-negative and HPV-positive). We combined, for the first time, research on macromolecular and low-molecular-weight compounds of latex-bearing plants in contrast to other studies that investigated proteins and alkaloids separately. The observed interaction between latex protein and alkaloids may influence our knowledge on plant defense. The proposed toolbox may help in further understanding of plant disease resistance and in pharmacological research.

Highlights

Extracts and latex of C. majus are used to treat warts and condylomas caused by human papillomavirus (HPV) [9]
The results suggest that the fractions containing CmMLP1 accompanied by alkaloids present the highest cytotoxic activity against cervical cancer HPV positive cells—less than 10% living cells left for each fraction (Figure 7a,c; Table 3)
The cell viability was the lowest for human epithelial cancer cell line (HeLa) HPV positive cells—with less than 10%

Summary

Introduction

Chelidonium majus L. is a perennial herbal plant belonging to the family Papaveraceae that grows across Europe, western Asia, and North America [1,2,3]. It is a rich source of different biologically active substances (alkaloids, flavonoids, phenolic acids) and has been used in folk medicine for centuries. The medicinal interest in C. majus is based mainly on small molecules such as alkaloids, flavonoids, and phenolic acids, which may act synergistically [4,5,10] These compounds exhibit antitumor, antiviral, and antibacterial activities [5,11]. Nucleases present in milky sap were found to exert apoptotic effects on a human cervical cancer HeLa cell line [12,13]

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