MOLECULAR DESIGN OF SUGAR-FREE MIGRACIN ANALOG MIGRACINAL THAT INHIBITS OVARIAN CANCER CELL MIGRATION AND INVASION

Abstract

Introduction. Cancer metastasis consists of several steps including detachment from the primary tumor, migration, invasion, transport in the blood or lymphatic vessels, attachment at the secondary site, and growth of secondary tumor. Migration and invasion areinvolved in the mechanism of all types of cancer metastasis. We previously isolated novel cellular migration inhibitor migracin A and B from a culture filtrate of Streptomyces sp. Migracin A was shown to inhibit IGF-1-mediated cellular migration and invasion in ovarian carcinoma cells. However, it is difficult to prepare large amount of migracin A. Migracin A consists of substituted benzene and an alkylated sugar moiety. In the present research, we have designed and synthesized a simplified dialdehydederivative of migracin called migracinal having no sugar moiety. Material and methods. Migracinal was purchased from Techno Chem Co., Ltd., Tokyo, Japan. Migracinal was prepared from 2,4-dihydroxybenzaldehyde (2,4-DHBA). The structure was confirmed by proton and carbon NMR spectra and ESI mass spectroscopy. The antitumor activity of the new derivative was studied by standard tests under conditions in vitro. Results. Migracinal inhibited cellular migration and invasion in ovarian clear cell carcinoma ES-2 cells. It also inhibited IGF-1 expression as migracin A. Moreover, it induced anoikis rather than apoptosis in ES-2 cells.Conclusions. Migracinal is easier to prepare than migracins, and it may be useful for the mechanistic study and suppression of metastasis.

Keywords

• migracinal
• migracin
• миграции
• инвазия
• аноикис
• рак яичника