Different cell death responses induced by eupomatenoid-5 in MCF-7 and 786-0 tumor cell lines

Author(s)

Longato, Giovanna Barbarini ^{[1, 2]} ; Fiorito, Giovanna Francisco ^[1] ; Vendramini-Costa, Debora Barbosa ^[1] ; de Oliveira Sousa, Ilza Maria ^[3] ; Tinti, Sirlene Valerio ^[1] ; Tasca Gois Ruiz, Ana Lucia ^[1] ; Vitalino de Almeida, Sinara Monica ^{[4, 5, 6]} ; Ribeiro Padilha, Rafael Jose ^{[4, 5]} ; Foglio, Mary Ann ^[3] ; de Carvalho, Joao Ernesto ^{[1, 7]}

Affiliation

^[1] Univ Estadual Campinas, Ctr Pluridisciplinar Pesquisas Quim Biol & Agr CP, Div Farmacol & Toxicol, BR-13083970 Campinas, SP - Brazil

^[2] Univ Estadual Campinas UNICAMP, Programa Posgrad Biol Celular & Estrutural, Inst Biol, BR-13083872 Campinas, SP - Brazil

^[3] Univ Estadual Campinas, CPQBA, Div Fitoquim, BR-13083970 Campinas, SP - Brazil

^[4] Univ Fed Pernambuco UFPE, LIKA, BR-50670901 Recife, PE - Brazil

^[5] Univ Fed Pernambuco UFPE, Dept Bioquim, BR-50670901 Recife, PE - Brazil

^[6] Univ Pernambuco UPE, Fac Ciencias Educ & Tecnol Garanhuns FACETEG, BR-55290000 Garanhuns, PE - Brazil

^[7] Univ Estadual Campinas, Fac Ciencias Farmaceut, BR-13083872 Campinas, SP - Brazil

• Document type: Journal article
• Source: TOXICOLOGY IN VITRO; v. 29, n. 5, p. 1026-1033, AUG 2015.
• Web of Science Citations: 12

Abstract

Natural products remain an important source of new drugs, including anticancer drugs. Recently, our group reported the anticancer activity of eupomatenoid-5 (eup-5), a neolignan isolated from Piper regnellii (Miq.) C. DC. var. regnellii leaves. In vitro studies demonstrated that MCF-7 (breast) and 786-0 (kidney) were among the cancer cell lines most sensitive to eup-5 treatment. The current results demonstrate that mitochondrial membrane depolarization and generation of reactive oxygen species are implicated in eup-5-mediated cytotoxic effects on these cancer cells lines. In MCF-7 cells, eup-5 led to phosphatidylserine externalization and caspase activation, whereas the same did not occur in 786-0 cells. Scanning electron microscopy revealed a reduction of microvilli density, as well as cell morphology alterations. Moreover, treated MCF-7 cells exhibited well-characterized apoptosis alterations, while treated 786-0 cells exhibited characteristics of programmed necroptosis process. These findings support the possibility that different mechanisms may be targeted by eup-5 in cell death response. (C) 2015 Elsevier Ltd. All rights reserved. (AU)