Lycorine hydrochloride inhibits metastatic melanoma cell-dominant vasculogenic mimicry.

Abstract

Melanoma cells actively participate in tumor angiogenesis and vasculogenic mimicry. However, anti-angiogenic therapy in patients with melanoma has not shown a significant survival gain. Thus, new anti-melanoma angiogenic and vasculogenic drugs are highly desired. Using the metastatic melanoma cell line C8161 as a model, we explored melanoma vasculogenic inhibitors and found that lycorine hydrochloride (LH) effectively suppressed C8161 cell-dominant formation of capillary-like tubes in vitro and generation of tumor blood vessels in vivo with low toxicity. Mechanistic studies revealed that LH markedly hindered expression of VE-cadherin in C8161 cells, but did not affect expression of six other important angiogenic and vasculogenic genes. Luciferase assays showed that LH significantly impeded promoter activity of the VE-cadherin gene in a dose-dependent manner. Together, these data suggest that LH inhibits melanoma C8161 cell-dominant vasculogenic mimicry by reducing VE-cadherin gene expression and diminishing cell surface exposure of the protein.

• Authors: Ruifang Liu, Zhifei Cao, Jian Tu, Yanyan Pan, Bingxue Shang, Gaochuan Zhang, Meimei Bao, Shasha Zhang, Ping Yang, Quansheng Zhou
• Journal: Pigment cell & melanoma research (Pigment Cell Melanoma Res) Vol. 25 Issue 5 Pg. 630-8 (Sep 2012) ISSN: 1755-148X [Electronic] England
• PMID: 22781316 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 John Wiley & Sons A/S.

Chemical References

• Amaryllidaceae Alkaloids
• Antigens, CD
• Cadherins
• Phenanthridines
• cadherin 5
• lycorine

Topics

• Amaryllidaceae Alkaloids (pharmacology, therapeutic use)
• Animals
• Antigens, CD (genetics, metabolism)
• Cadherins (genetics, metabolism)
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic
• Humans
• Melanoma (blood supply, drug therapy, genetics, pathology)
• Mice
• Models, Biological
• Neoplasm Metastasis
• Neovascularization, Pathologic (drug therapy, pathology)
• Phenanthridines (pharmacology, therapeutic use)
• Promoter Regions, Genetic (genetics)
• Skin Neoplasms (blood supply, drug therapy, genetics, pathology)