Effect of chelidonine on growth, invasion, angiogenesis and gene expression in head and neck cancer cell lines

Abstract

The greater celandine ‘Chelidonium majus’ and its main alkaloid chelidonine have previously been shown to exert high cytotoxicity against cancer cells. Furthermore, chelidonine is proposed to possess pro-apoptotic and anti-metastatic properties. Within the present study, the effects chelidonine on several HNSCC cell lines, as well as primary cells, were analyzed with respect to growth, migration, angiogenesis and apoptosis. Chelidonine suppressed the growth of all tested HNSCC cell lines, including a paclitaxel-resistant and P-glycoprotein (MDR1) overexpressing cell line, but not in a clear dose-dependent manner. Mucosal keratinocytes were also strongly affected by chelidonine, while fibroblasts proved to be much more resistant. Chelidonine failed to trigger apoptosis at physiological concentrations in HNSCC cell lines. Based on a spheroid invasion model chelidonine suppressed invasion of FaDu cells effectively on gelatin, fibronectin, collagen I, laminin and Matrigel®. However, invasion inhibition of the more aggressively invading cell line HLaC78 largely failed. Using the tube formation assay, chelidonine effectively inhibited angiogenesis. Expression analysis revealed an upregulation of the xenobiotic metabolism genes CYP1A1 and MDR1 by chelidonine. In summary, chelidonine appeared to exert only minor impact on head and neck cancer cells. Chelidonine did not produce clear dose-dependent and cell-type specific cytotoxicity nor did it trigger apoptosis strongly.

The Effects of Traditional Chinese Medicine on P-Glycoprotein–Mediated Multidrug Resistance and Approaches for Studying the Herb–P-Glycoprotein Interactions

“…Besides, there exists a large number of natural alkaloids possessing potent inhibition of the P-gp responsible for the development of Pusztai et al, 2005 resistance (Joshi et al, 2017). Chelidonine, isolated from Chelidonium majus, could also inhibit the function of P-gp and consequently upregulate the xenobiotic metabolism genes CYP1A1 and MDR1 (Herrmann et al, 2018). Matrine, isolated from Sophora flavescens, is another quinolizidine alkaloid that has an inhibition effect on P-gp.…”

Effects of Abiotic Elicitors on Expression and Accumulation of Three Candidate Benzophenanthridine Alkaloids in Cultured Greater Celandine Cells

“…Greater Celandine ( Chelidonium majus L.) is a biennial/perennial plant native to Europe and North Asia [ 1 ]. It is a promising medicinal plant in terms of traditional and modern pharmacology, which covers a range of valuable phytochemicals, most notably anti-cancer chelidonine [ 2 ], anti-inflammatory berberine [ 3 ], and anti-bacteria sanguinarine [ 4 ]. This plant is well-known for its lead in the industry of anti-cancer plant-derived medicines [ 5 , 6 ].…”

Chelidonine Induces Apoptosis via GADD45a-p53 Regulation in Human Pancreatic Cancer Cells

“… 1 , 2 Chelidonine is known for its broad pharmacological activities that lead to anti-inflammation, anti-viral and anti-cancer effects. 3 - 5 To be specific, chelidonine treatment induced apoptosis in T98G glioma cells, MCF-7 and SK-BR-3 breast adenocarcinoma, HepG2 hepatoma, HeLa cervical cancer, SW620 colon cancer, head and neck squamous cell carcinoma HNSCC, human gastric carcinoma SGC-7901, and leukemia MT-4 cells, through caspase, cell cycle checkpoints and MAP Kinase pathways. 3 , 6 - 12 In colon cancer Caco-2 and leukemia cell line CEM/ADR 5000, metabolic enzyme regulation by chelidonine reversed doxorubicin resistance.…”