ANTI-INVASIVE ACTIVITY OF ALKALOIDS AND POLYPHENOLICS IN-VITRO

Invasiveness, the ability of certain tumour cells to migrate beyond th eir natural tissue boundaries, often leads to metastasis, and usually determines the fatal outcome of cancer. The need for anti-invasive age nts has led us to search for possibly active compounds among alkaloids and polyphenolics. One hundred compounds were screened in an assay ba sed on the confrontation of invasive human MCF-7/6 mammary carcinoma c ells with fragments of normal embryonic chick heart in vitro. Anti-inv asive activity was frequently found among chalcones having a prenyl gr oup. Six compounds were found to inhibit invasion when added to the cu lture medium at concentrations as low as 1 mu M. For at least three of them the anti-invasive effect could be associated with a cytotoxic ef fect on the MCF-7/6 cells, but not on the heart tissue. This selective cytotoxicity was substantiated by different methods, such as histolog y and growth assays (volume measurements, cell counts, MTT and sulforh odamine B assays). The anti-invasive effects of the compounds could ne ither be ascribed to induction of apoptosis nor to the promotion of ce ll-cell adhesion. Our data indicate that among the alkaloids and polyp henolics a number of molecules can inhibit growth and invasion of huma n mammary cancer cells via selective cytotoxicity. (C) 1997 Elsevier S cience Ltd.