Anti-invasive activity of alkaloids and polyphenolics in vitro

• Published in: Bioorganic & medicinal chemistry Vol. 5; no. 8; pp. 1609 - 1619
• Main Authors: Parmar, Virinder S., Bracke, Marc E., Philippe, Jan, Wengel, Jesper, Jain, Subhash C., Olsen, Carl E., Bisht, Kirpal S., Sharma, Nawal K., Courtens, Andy, Sharma, Sunil K., Vennekens, Krist'l, Van Marck, Veerle, Singh, Sanjay K., Kumar, Naresh, Kumar, Ajay, Malhotra, Sanjay, Kumar, Rajesh, Rajwanshi, Vivek K., Jain, Rajni, Mareel, Marc M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.1997
• Subjects: Alkaloids - chemistry; Alkaloids - pharmacology; Animals; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Chick Embryo; Flavonoids - chemistry; Flavonoids - pharmacology; Heart - drug effects; Humans; Models, Molecular; Myocardium - cytology; Neoplasm Invasiveness; Phenols - chemistry; Phenols - pharmacology; Structure-Activity Relationship; Tumor Cells, Cultured - drug effects
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/S0968-0896(97)00091-6

Invasiveness, the ability of certain tumour cells to migrate beyond their natural tissue boundaries, often leads to metastasis, and usually determines the fatal outcome of cancer. The need for anti-invasive agents has led us to search for possibly active compounds among alkaloids and polyphenolics. One hundred compounds were screened in an assay based on the confrontation of invasive human MCF-7/6 mammary carcinoma cells with fragments of normal embryonic chick heart in vitro. Anti-invasive activity was frequently found among chalcones having a prenyl group. Six compounds were found to inhibit invasion when added to the culture medium at concentrations as low as 1 μM. For at least three of them the anti-invasive effect could be associated with a cytotoxic effect on the MCF-7/6 cells, but not on the heart tissue. This selective cytotoxicity was substantiated by different methods, such as histology and growth assays (volume measurements, cell counts, MTT and sulforhodamine B assays). The anti-invasive effects of the compounds could neither be ascribed to induction of apoptosis nor to the promotion of cell-cell adhesion. Our data indicate that among the alkaloids and polyphenolics a number of molecules can inhibit growth and invasion of human mammary cancer cells via selective cytotoxicity. Among 100 alkaloids and flavonoids tested for anti-invasive activity, six compounds inhibited the invasion of human MCF-7/6 mammary carcinoma cells in confronting cultures with embryonic chick heart fragments at a concentration of 1 μM. Chalcones bearing prenyl group(s) have shown the best activity.