Amaryllidaceae Alkaloids Decrease the Proliferation, Invasion, and Secretion of Clinically Relevant Cytokines by Cultured Human Colon Cancer Cells

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2022-09, Vol.12 (9), p.1267
• Main Authors: Mathieu, Veronique, Laguera, Breana, Masi, Marco, Dulanto, Sara Adriana, Bingham, Tanner W, Hernandez, Lucas W, Sarlah, David, Evidente, Antonio, Lafontaine, Denis L J, Kornienko, Alexander, Lane, Michelle A
• Format: Article
• Language: English
• Subjects: Acids; Alkaloids; Alkaloids - pharmacology; Amaryllidaceae; Amaryllidaceae Alkaloids - pharmacology; Antitumor agents; Cancer; Cancer cells; Cancer therapies; Care and treatment; Cell adhesion & migration; Cell Line; Cell Proliferation; Colon cancer; Colonic Neoplasms - drug therapy; Colorectal cancer; Colorectal carcinoma; Cytokines; Drug development; Evaluation; Experiments; haemanthamine; Health aspects; Hippocrates (460?-377? BC); Humans; Inflammation; Interstitial collagenase; Kinases; Laboratories; lycorine; Matrix metalloproteinase; Matrix Metalloproteinase 1; Metastasis; Mutation; narciclasine; pancratistatin; Pentraxins; Phenanthridines; Physiological aspects; Tumor necrosis factor-TNF; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - pharmacology
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom12091267

Alkaloids isolated from members of the plant family are promising anticancer agents. The purpose of the current study was to determine if the isocarbostyrils narciclasine, pancratistatin, lycorane, lycorine, crinane, and haemanthamine inhibit phenomena related to cancer progression in vitro. To achieve this, we examined the proliferation, adhesion, and invasion of cultured human colon cancer cells via MTT assay and Matrigel-coated Boyden chambers. In addition, Luminex assays were used to quantify the secretion of matrix metalloproteinases (MMP) and cytokines associated with poor clinical outcomes. We found that all alkaloids decreased cell proliferation regardless of TP53 status, with narciclasine exhibiting the greatest potency. The effects on cell proliferation also appear to be specific to cancer cells. Narciclasine, lycorine, and haemanthamine decrease both adhesion and invasion but with various potencies depending on the cell line. In addition, narciclasine, lycorine, and haemanthamine decreased the secretion of MMP-1, -2, and -7, as well as the secretion of the cytokines pentraxin 3 and vascular endothelial growth factor. In conclusion, the present study shows that Amaryllidaceae alkaloids decrease phenomena and cytokines associated with colorectal cancer progression, supporting future investigations regarding their potential as multifaceted drug candidates.