Annona coriacea Mart. Fractions Promote Cell Cycle Arrest and Inhibit Autophagic Flux in Human Cervical Cancer Cell Lines

Autor: Bruno G. Oliveira, Wanderson Romão, Renato José Silva-Oliveira, Rui Manuel Reis, Izabela Natalia Faria Gomes, Marcela N. Rosa, Maria Cristina Da Silva Barbosa, Fábio Vieira dos Santos, Viviane Aline Oliveira Silva, Patrik Da Silva Vital, João Gabriel M. Junqueira, Rosy Iara Maciel de Azambuja Ribeiro, Vanessa Gisele Pasqualotto Severino
Přispěvatelé: Universidade do Minho
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Cell cycle checkpoint
cervical cancer
Medicina Básica [Ciências Médicas]
Pharmaceutical Science
Uterine Cervical Neoplasms
Apoptosis
Annona
Analytical Chemistry
HeLa
0302 clinical medicine
Drug Discovery
0303 health sciences
biology
Chemistry
Cell cycle
3. Good health
Chemistry (miscellaneous)
cell cycle arrest
030220 oncology & carcinogenesis
Ciências Médicas::Medicina Básica
Molecular Medicine
Female
Intracellular
medicine.drug
Signal Transduction
autophagy
Natural compounds
Article
Cell cycle arrest
lcsh:QD241-441
03 medical and health sciences
lcsh:Organic chemistry
Autophagy
medicine
natural compounds
Humans
Physical and Theoretical Chemistry
030304 developmental biology
Cell Proliferation
Cisplatin
Science & Technology
Cell growth
Plant Extracts
Organic Chemistry
Cell Cycle Checkpoints
biology.organism_classification
Cell culture
Drug Resistance
Neoplasm
Cervical cancer
Cancer research
HeLa Cells
Zdroj: Molecules, Vol 24, Iss 21, p 3963 (2019)
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
Molecules
Volume 24
Issue 21
ISSN: 1420-3049
Popis: Plant-based compounds are an option to explore and perhaps overcome the limitations of current antitumor treatments. Annona coriacea Mart. is a plant with a broad spectrum of biological activities, but its antitumor activity is still unclear. The purpose of our study was to determine the effects of A. coriacea fractions on a panel of cervical cancer cell lines and a normal keratinocyte cell line. The antitumor effect was investigated in vitro by viability assays, cell cycle, apoptosis, migration, and invasion assays. Intracellular signaling was assessed by Western blot, and major compounds were identified by mass spectrometry. All fractions exhibited a cytotoxic effect on cisplatin-resistant cell lines, SiHa and HeLa. C3 and C5 were significantly more cytotoxic and selective than cisplatin in SiHa and Hela cells. However, in CaSki, a cisplatin-sensitive cell line, the compounds did not demonstrate higher cytotoxicity when compared with cisplatin. Alkaloids and acetogenins were the main compounds identified in the fractions. These fractions also markedly decreased cell proliferation with p21 increase and cell cycle arrest in G2/M. These effects were accompanied by an increase of H2AX phosphorylation levels and DNA damage index. In addition, fractions C3 and C5 promoted p62 accumulation and decrease of LC3II, as well as acid vesicle levels, indicating the inhibition of autophagic flow. These findings suggest that A. coriacea fractions may become effective antineoplastic drugs and highlight the autophagy inhibition properties of these fractions in sensitizing cervical cancer cells to treatment.
e FINEP (MCTI/FINEP/MS/SCTIE/DECIT-01/ 2013—FP XII-BIOPLAT), Barretos Cancer Hospital, CAPES, CNPq, FAPEMIG, UFSJ. RMR is a recipient of CNPq Productivity Grant
Databáze: OpenAIRE
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