Pharmaceutica Analytica Acta

Effects of spiro-bis heterocycles on proliferation and apoptosis in human breast cancer cell lines

Joint Event on Euro Structural Biology & Clinical Trials and NanoPharma

March 18-19, 2019 | Paris, France

Lamia Hamdan Ramdani, Oualid Talhi, Nadia Taibi, Laetitia Delort, Caroline Decombat, Artur Silva and Khaldoun Bachari, Marie-PauleVasson and Florence Caldefie-Chezet

CRAPC, Algeria University Clermont Auvergne, France Research Center in Human Nutrition CRNH Auvergne, France Anticancer Center Jean-Perrin, France University of Aveiro, Portugal

Posters & Accepted Abstracts: Pharm Anal Acta

Abstract:

Breast cancer is the first cause of cancer death in women worldwide and a major concern to public health. The main axes of this work consist in studying the antiproliferative and pro-apoptotic effects of spiro-bis heterocycles on human breast cancer cell lines MCF-7 and MDA-MB-231. On the structural point of view, the compounds feature a hydantoin moiety attached either to diazole, isoxazole, diazepine, oxazepine or benzodiazepine via the privileged tetrahedral spiro-linkage. The treatment with compounds three and six, corresponding to spiro [hydantoin-isoxazole] and spiro [hydantoin-oxazepine] respectively, resulted in a significant decrease of cell proliferation and the induction of the apoptosis in both breast cancer cell lines. However, the compound four (spiro [hydantoin-diazepine]) demonstrated an antiproliferative activity only against MDA-MB-231. The qRT-PCR revealed an up-regulation of MDM2, strictly p53-dependent, and an increase of the expression of pro-apoptotic genes such as caspase 3 and BAX in MCF-7 wild-type p53 and MDA-MB-231 mutant p53 breast cancer cells. In summary, the results suggested that our compounds promoted the apoptosis of breast cancer cell lines through p53- dependent and independent pathways.

Biography :

E-mail: lamia_pharm@yahoo.fr