A tetraprenylated benzophenone 7-epiclusianone induces cell cycle arrest at G1/S transition by modulating critical regulators of cell cycle in breast cancer cell lines

Author(s):Show less -

Lamartine-Hanemann, Simone da Silva ^[1] ; Ferreira-Silva, Guilherme Alvaro ^[1] ; Horvath, Renato de Oliveira ^[1] ; Soncini, Roseli ^[1] ; Caixeta, Ester Siqueira ^[1] ; Rocha-Sales, Bianca ^[2] ; Niero, Evandro Luis ^[2] ; Machado-Santelli, Glaucia Maria ^[2] ; dos Santos, Marcelo Henrique ^[3] ; de Oliveira, Jaqueline Carvalho ^[4] ; Miyazawa, Marta ^[5] ; Ionta, Marisa ^[1]

Affiliation

^[1] Univ Fed Alfenas, Inst Ciencias Biomed, Rua Gabriel Monteiro da Silva 700, Alfenas, MG - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Sao Paulo, SP - Brazil

^[3] Univ Fed Vicosa, Dept Quim, Vicosa, MG - Brazil

^[4] Univ Fed Parana, Dept Genet, Setor Ciencias Biol, Curitiba, Parana - Brazil

^[5] Univ Fed Alfenas, Fac Odontol, Rua Gabriel Monteiro da Silva 700, Alfenas, MG - Brazil

• Document type: Journal article
• Source: TOXICOLOGY IN VITRO; v. 68, OCT 2020.
• Web of Science Citations: 0

Abstract

Breast cancer is a complex disease and encompassing different types of tumor. Although advances in understanding of the molecular bases of breast cancer biology, the therapeutic proposals available still are not effective. In this scenario, the present study aimed to evaluate the mechanisms associated to antitumor activity of 7-Epiclusianone (7-Epi), a tetraprenylated benzophenone, on luminal A (MCF-7) and claudin-low (Hs 578T) breast cancer cell lines. We found that 7-Epi efficiently inhibited cell proliferation and migration of these cells; however MCF-7 was slightly more responsive than Hs 578T. Cell cycle analysis showed accumulation of cells at G0/G1 phase with drastic reduction of S population in treated cultures. This effect was associated to down-regulation of CDKN1A (p21) and cyclin E in both cell lines. In addition, 7-Epi reduced cyclin D1 and p-ERK expression levels in MCF-7 cell line. Cytotoxic effect of 7-Epi on breast cancer cell lines was associated to its ability to increase BAX/BCL-2 ratio. In conclusion, our findings showed that 7-Epi is a promising antitumor agent against breast cancer by modulating critical regulators of the cell cycle and apoptosis. (AU)

• FAPESP's process: 09/53840-0 - Fluorescence system for investigations of physiological and pathophysiological aspects in cellular models
• Grantee: Adriana Karaoglanovic Carmona
• Support Opportunities: Multi-user Equipment Program