Anticancer Activity and Molecular Targets of <i>Piper cernuum</i> Substances in Oral Squamous Cell Carcinoma Models
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. <i>Piper</i> plant species have shown many biological activities. In the present study, we show that dichloromethane...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| 格式: | 文件 |
| 语言: | English |
| 出版: |
MDPI AG
2023-07-01
|
| 丛编: | Biomedicines |
| 主题: | |
| 在线阅读: | https://www.mdpi.com/2227-9059/11/7/1914 |
| _version_ | 1827733752865882112 |
|---|---|
| author | Thaíssa Queiróz Machado Maria Emanuelle Damazio Lima Rafael Carriello da Silva Arthur Ladeira Macedo Lucas Nicolau de Queiroz Bianca Roberta Peres Angrisani Anna Carolina Carvalho da Fonseca Priscilla Rodrigues Câmara Vitor Von-Held Rabelo Carlos Alexandre Carollo Davyson de Lima Moreira Elan Cardozo Paes de Almeida Thatyana Rocha Alves Vasconcelos Paula Alvarez Abreu Alessandra Leda Valverde Bruno Kaufmann Robbs |
| author_facet | Thaíssa Queiróz Machado Maria Emanuelle Damazio Lima Rafael Carriello da Silva Arthur Ladeira Macedo Lucas Nicolau de Queiroz Bianca Roberta Peres Angrisani Anna Carolina Carvalho da Fonseca Priscilla Rodrigues Câmara Vitor Von-Held Rabelo Carlos Alexandre Carollo Davyson de Lima Moreira Elan Cardozo Paes de Almeida Thatyana Rocha Alves Vasconcelos Paula Alvarez Abreu Alessandra Leda Valverde Bruno Kaufmann Robbs |
| author_sort | Thaíssa Queiróz Machado |
| collection | DOAJ |
| description | 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. <i>Piper</i> plant species have shown many biological activities. In the present study, we show that dichloromethane partition of <i>Piper cernuum</i> (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 <i>P. cernuum</i> 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 <i>P. cernuum</i> fractions point to promising compounds as new preclinical anticancer candidates. |
| first_indexed | 2024-03-11T01:16:33Z |
| format | Article |
| id | doaj.art-4f52034087fb4215b5dd079c8feab9bd |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T01:16:33Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-4f52034087fb4215b5dd079c8feab9bd2023-11-18T18:26:46ZengMDPI AGBiomedicines2227-90592023-07-01117191410.3390/biomedicines11071914Anticancer Activity and Molecular Targets of <i>Piper cernuum</i> Substances in Oral Squamous Cell Carcinoma ModelsThaíssa Queiróz Machado0Maria Emanuelle Damazio Lima1Rafael Carriello da Silva2Arthur Ladeira Macedo3Lucas Nicolau de Queiroz4Bianca Roberta Peres Angrisani5Anna Carolina Carvalho da Fonseca6Priscilla Rodrigues Câmara7Vitor Von-Held Rabelo8Carlos Alexandre Carollo9Davyson de Lima Moreira10Elan Cardozo Paes de Almeida11Thatyana Rocha Alves Vasconcelos12Paula Alvarez Abreu13Alessandra Leda Valverde14Bruno Kaufmann Robbs15Postgraduate Program in Applied Science for Health Products, Faculty of Pharmacy, Fluminense Federal University, Niteroi 24241-000, RJ, BrazilDepartment of Organic Chemistry, Chemistry Institute, Fluminense Federal University, Niteroi 24020-141, RJ, BrazilPostgraduate Program in Dentistry, Health Institute of Nova Friburgo, Fluminense Federal University, Nova Friburgo 28625-650, RJ, BrazilPharmaceutical Sciences, Food and Nutrition Faculty, Mato Grosso do Sul Federal University, Campo Grande 79070-900, MS, BrazilPostgraduate Program in Applied Science for Health Products, Faculty of Pharmacy, Fluminense Federal University, Niteroi 24241-000, RJ, BrazilDepartment of Organic Chemistry, Chemistry Institute, Fluminense Federal University, Niteroi 24020-141, RJ, BrazilPostgraduate Program in Dentistry, Health Institute of Nova Friburgo, Fluminense Federal University, Nova Friburgo 28625-650, RJ, BrazilBasic Science Department, Health Institute of Nova Friburgo, Fluminense Federal University, Nova Friburgo 28625-650, RJ, BrazilBiodiversity and Sustainability Institute, Macaé Campus, Federal University of Rio de Janeiro, Macae 21941-901, RJ, BrazilPharmaceutical Sciences, Food and Nutrition Faculty, Mato Grosso do Sul Federal University, Campo Grande 79070-900, MS, BrazilResearch Directorate, Laboratory of Natural Products and Biochemistry, Rio de Janeiro Botanical Garden Research Institute, Rio de Janeiro 22460-030, RJ, BrazilBasic Science Department, Health Institute of Nova Friburgo, Fluminense Federal University, Nova Friburgo 28625-650, RJ, BrazilDepartment of Organic Chemistry, Chemistry Institute, Fluminense Federal University, Niteroi 24020-141, RJ, BrazilBiodiversity and Sustainability Institute, Macaé Campus, Federal University of Rio de Janeiro, Macae 21941-901, RJ, BrazilDepartment of Organic Chemistry, Chemistry Institute, Fluminense Federal University, Niteroi 24020-141, RJ, BrazilBasic Science Department, Health Institute of Nova Friburgo, Fluminense Federal University, Nova Friburgo 28625-650, RJ, BrazilOral 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. <i>Piper</i> plant species have shown many biological activities. In the present study, we show that dichloromethane partition of <i>Piper cernuum</i> (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 <i>P. cernuum</i> 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 <i>P. cernuum</i> fractions point to promising compounds as new preclinical anticancer candidates.https://www.mdpi.com/2227-9059/11/7/1914oral cancerPiperaceaeGNPSantitumorapoptosisisocorydine |
| spellingShingle | Thaíssa Queiróz Machado Maria Emanuelle Damazio Lima Rafael Carriello da Silva Arthur Ladeira Macedo Lucas Nicolau de Queiroz Bianca Roberta Peres Angrisani Anna Carolina Carvalho da Fonseca Priscilla Rodrigues Câmara Vitor Von-Held Rabelo Carlos Alexandre Carollo Davyson de Lima Moreira Elan Cardozo Paes de Almeida Thatyana Rocha Alves Vasconcelos Paula Alvarez Abreu Alessandra Leda Valverde Bruno Kaufmann Robbs Anticancer Activity and Molecular Targets of <i>Piper cernuum</i> Substances in Oral Squamous Cell Carcinoma Models Biomedicines oral cancer Piperaceae GNPS antitumor apoptosis isocorydine |
| title | Anticancer Activity and Molecular Targets of <i>Piper cernuum</i> Substances in Oral Squamous Cell Carcinoma Models |
| title_full | Anticancer Activity and Molecular Targets of <i>Piper cernuum</i> Substances in Oral Squamous Cell Carcinoma Models |
| title_fullStr | Anticancer Activity and Molecular Targets of <i>Piper cernuum</i> Substances in Oral Squamous Cell Carcinoma Models |
| title_full_unstemmed | Anticancer Activity and Molecular Targets of <i>Piper cernuum</i> Substances in Oral Squamous Cell Carcinoma Models |
| title_short | Anticancer Activity and Molecular Targets of <i>Piper cernuum</i> Substances in Oral Squamous Cell Carcinoma Models |
| title_sort | anticancer activity and molecular targets of i piper cernuum i substances in oral squamous cell carcinoma models |
| topic | oral cancer Piperaceae GNPS antitumor apoptosis isocorydine |
| url | https://www.mdpi.com/2227-9059/11/7/1914 |
| work_keys_str_mv | AT thaissaqueirozmachado anticanceractivityandmoleculartargetsofipipercernuumisubstancesinoralsquamouscellcarcinomamodels AT mariaemanuelledamaziolima anticanceractivityandmoleculartargetsofipipercernuumisubstancesinoralsquamouscellcarcinomamodels AT rafaelcarriellodasilva anticanceractivityandmoleculartargetsofipipercernuumisubstancesinoralsquamouscellcarcinomamodels AT arthurladeiramacedo anticanceractivityandmoleculartargetsofipipercernuumisubstancesinoralsquamouscellcarcinomamodels AT lucasnicolaudequeiroz anticanceractivityandmoleculartargetsofipipercernuumisubstancesinoralsquamouscellcarcinomamodels AT biancarobertaperesangrisani anticanceractivityandmoleculartargetsofipipercernuumisubstancesinoralsquamouscellcarcinomamodels AT annacarolinacarvalhodafonseca anticanceractivityandmoleculartargetsofipipercernuumisubstancesinoralsquamouscellcarcinomamodels AT priscillarodriguescamara anticanceractivityandmoleculartargetsofipipercernuumisubstancesinoralsquamouscellcarcinomamodels AT vitorvonheldrabelo anticanceractivityandmoleculartargetsofipipercernuumisubstancesinoralsquamouscellcarcinomamodels AT carlosalexandrecarollo anticanceractivityandmoleculartargetsofipipercernuumisubstancesinoralsquamouscellcarcinomamodels AT davysondelimamoreira anticanceractivityandmoleculartargetsofipipercernuumisubstancesinoralsquamouscellcarcinomamodels AT elancardozopaesdealmeida anticanceractivityandmoleculartargetsofipipercernuumisubstancesinoralsquamouscellcarcinomamodels AT thatyanarochaalvesvasconcelos anticanceractivityandmoleculartargetsofipipercernuumisubstancesinoralsquamouscellcarcinomamodels AT paulaalvarezabreu anticanceractivityandmoleculartargetsofipipercernuumisubstancesinoralsquamouscellcarcinomamodels AT alessandraledavalverde anticanceractivityandmoleculartargetsofipipercernuumisubstancesinoralsquamouscellcarcinomamodels AT brunokaufmannrobbs anticanceractivityandmoleculartargetsofipipercernuumisubstancesinoralsquamouscellcarcinomamodels |