Acetogenins-Rich Fractions of <i>Annona coriacea</i> Suppress Human Glioblastoma Viability and Migration by Regulating Necroptosis and MMP-2 Activity In Vitro
Lorena R. Sousa,
Ana Gabriela S. Oliveira,
Antônio Arantes,
João Gabriel M. Junqueira,
Gerso P. Alexandre,
Vanessa G. P. Severino,
Rui Manuel Reis,
Bonglee Kim,
Rosy I. M. A. Ribeiro
Affiliations
Lorena R. Sousa
Experimental Pathology Laboratory, Federal University of São João del Rei (UFSJ), 400, Sebastião Gonçalves Coelho, Chanadour, Divinópolis 35501-296, MG, Brazil
Ana Gabriela S. Oliveira
Experimental Pathology Laboratory, Federal University of São João del Rei (UFSJ), 400, Sebastião Gonçalves Coelho, Chanadour, Divinópolis 35501-296, MG, Brazil
Antônio Arantes
Experimental Pathology Laboratory, Federal University of São João del Rei (UFSJ), 400, Sebastião Gonçalves Coelho, Chanadour, Divinópolis 35501-296, MG, Brazil
João Gabriel M. Junqueira
Institute of Chemistry, Federal University of Goiás (UFG), University Campus, Goiânia 74968-755, GO, Brazil
Gerso P. Alexandre
Institute of Chemistry, Federal University of Goiás (UFG), University Campus, Goiânia 74968-755, GO, Brazil
Vanessa G. P. Severino
Institute of Chemistry, Federal University of Goiás (UFG), University Campus, Goiânia 74968-755, GO, Brazil
Rui Manuel Reis
Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos 14784-400, SP, Brazil
Bonglee Kim
College of Medicine, Kyung Hee University, Seoul 02453, Republic of Korea
Rosy I. M. A. Ribeiro
Experimental Pathology Laboratory, Federal University of São João del Rei (UFSJ), 400, Sebastião Gonçalves Coelho, Chanadour, Divinópolis 35501-296, MG, Brazil
Glioblastoma (GBM) is an incurable primary brain tumor with a poor prognosis. Resection, radiation therapy, and temozolomide (TMZ) are insufficient to increase survival, making the treatment limited. Thus, the search for more effective and specific treatments is essential, making plants a promising source for elucidating new anti-glioblastoma compounds. Accordingly, this study investigated the effects of four fractions of hexane and ethyl acetate extract of Annona coriacea Mart., enriched with acetogenins, against GBM cell lines. All four fractions were selectively cytotoxic to GBM cells when compared to TMZ. Moreover, A. coriacea fractions delayed cell migration; reduced cytoplasmic projections, the metalloproteinase 2 (MMP-2) activity; and induced morphological changes characteristic of necroptosis, possibly correlated with the increase in receptor-interacting protein kinase 1 and 3 (RIP-1 and RIP-3), apoptosis-inducing factor (AIF), and the non-activation of cleaved caspase 8. The present findings reinforce that fractions of A. coriacea Mart. should be considered for more studies focusing treatment of GBM.
