학술논문
Anticancer Activity and Molecular Targets of Piper cernuum Substances in Oral Squamous Cell Carcinoma Models.
Document Type
Academic Journal
Author
Machado TQ; Postgraduate Program in Applied Science for Health Products, Faculty of Pharmacy, Fluminense Federal University, Niteroi 24241-000, RJ, Brazil.; Lima MED; Department of Organic Chemistry, Chemistry Institute, Fluminense Federal University, Niteroi 24020-141, RJ, Brazil.; da Silva RC; Postgraduate Program in Dentistry, Health Institute of Nova Friburgo, Fluminense Federal University, Nova Friburgo 28625-650, RJ, Brazil.; Macedo AL; Pharmaceutical Sciences, Food and Nutrition Faculty, Mato Grosso do Sul Federal University, Campo Grande 79070-900, MS, Brazil.; de Queiroz LN; Postgraduate Program in Applied Science for Health Products, Faculty of Pharmacy, Fluminense Federal University, Niteroi 24241-000, RJ, Brazil.; Angrisani BRP; Department of Organic Chemistry, Chemistry Institute, Fluminense Federal University, Niteroi 24020-141, RJ, Brazil.; da Fonseca ACC; Postgraduate Program in Dentistry, Health Institute of Nova Friburgo, Fluminense Federal University, Nova Friburgo 28625-650, RJ, Brazil.; Câmara PR; Basic Science Department, Health Institute of Nova Friburgo, Fluminense Federal University, Nova Friburgo 28625-650, RJ, Brazil.; Rabelo VV; Biodiversity and Sustainability Institute, Macaé Campus, Federal University of Rio de Janeiro, Macae 21941-901, RJ, Brazil.; Carollo CA; Pharmaceutical Sciences, Food and Nutrition Faculty, Mato Grosso do Sul Federal University, Campo Grande 79070-900, MS, Brazil.; de Lima Moreira D; Research Directorate, Laboratory of Natural Products and Biochemistry, Rio de Janeiro Botanical Garden Research Institute, Rio de Janeiro 22460-030, RJ, Brazil.; de Almeida ECP; Basic Science Department, Health Institute of Nova Friburgo, Fluminense Federal University, Nova Friburgo 28625-650, RJ, Brazil.; Vasconcelos TRA; Department of Organic Chemistry, Chemistry Institute, Fluminense Federal University, Niteroi 24020-141, RJ, Brazil.; Abreu PA; Biodiversity and Sustainability Institute, Macaé Campus, Federal University of Rio de Janeiro, Macae 21941-901, RJ, Brazil.; Valverde AL; Department of Organic Chemistry, Chemistry Institute, Fluminense Federal University, Niteroi 24020-141, RJ, Brazil.; Robbs BK; Basic Science Department, Health Institute of Nova Friburgo, Fluminense Federal University, Nova Friburgo 28625-650, RJ, Brazil.
Source
Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101691304 Publication Model: Electronic Cited Medium: Print ISSN: 2227-9059 (Print) Linking ISSN: 22279059 NLM ISO Abbreviation: Biomedicines Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2227-9059
Abstract
Oral squamous cell carcinoma (OSCC) is a worldwide public health problem, with high morbidity and mortality rates. The development of new drugs to treat OSCC is paramount. Piper plant species have shown many biological activities. In the present study, we show that dichloromethane partition of Piper cernuum (PCLd) is nontoxic in chronic treatment in mice, reduces the amount of atypia in tongues of chemically induced OSCC, and significantly increases animal survival. To identify the main active compounds, chromatographic purification of PCLd was performed, where fractions 09.07 and 14.05 were the most active and selective. These fractions promoted cell death by apoptosis characterized by phosphatidyl serine exposition, DNA fragmentation, and activation of effector caspase-3/7 and were nonhemolytic. LC-DAD-MS/MS analysis did not propose matching spectra for the 09.07 fraction, suggesting compounds not yet known. However, aporphine alkaloids were annotated in fraction 14.05, which are being described for the first time in P. cernuum and corroborate the observed cytotoxic activity. Putative molecular targets were determined for these alkaloids, in silico, where the androgen receptor (AR), CHK1, CK2, DYRK1A, EHMT2, LXRβ, and VEGFR2 were the most relevant. The results obtained from P. cernuum fractions point to promising compounds as new preclinical anticancer candidates.