Casearin D inhibits ERK phosphorylation and induces downregulation of cyclin D1 in HepG2 cells.
Cancer is a public health problem which represents the second cause of death in the world. In this framework, it is necessary to identify novel compounds with antineoplastic potential. Plants are an important source for discovering novel compounds with pharmacological potential. In this study, we aimed to investigate the antiproliferative potential of isolated compounds from Casearia sylvestris on tumor cell lines. Crude extract effectively reduced cell viability of 4 tumor cell lines (HepG2, A549, U251-MG, and HT-144) after 48h treatment. HepG2 and HT-144 were the most responsive cells. Three fractions (aqueous ethanol, n-hexane and ethyl acetate) were tested against HepG2 and HT-144 cells and we observed that compounds with antiproliferative activity were concentrated in n-hexane and ethyl acetate fractions. The casearins A, G and J were isolated from n-hexane fraction, while casearin D was obtained from ethyl acetate fraction. We demonstrated that casearin D significantly inhibited the clonogenic capacity of HepG2 cells after 24h exposure indicating its antiproliferative activity. In addition, G1/S transition cell cycle arrest in HepG2 cells was also observed. These effects are related, at least in part, to ability of the casearin D in reducing ERK phosphorylation and cyclin D1 expression levels.
Institute of Biomedical Sciences, Federal University of Alfenas, Rua Gabriel Monteiro da Silva, 700, 37130-000, Alfenas, MG, Brazil.
Guilherme Álvaro
GÁ
Ferreira-Silva
Institute of Chemistry, Federal University of Alfenas, Rua Gabriel Monteiro da Silva, 700, 37130-000, Alfenas, MG, Brazil.
Carla Carolina Lopes
CCL
Lages
Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of Sao Paulo, Diadema, SP, Brazil.
Patricia
P
Sartorelli
Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of Sao Paulo, Diadema, SP, Brazil.
Flávia Rie
FR
Hasegawa
Institute of Chemistry, Federal University of Alfenas, Rua Gabriel Monteiro da Silva, 700, 37130-000, Alfenas, MG, Brazil.
Marisi Gomes
MG
Soares
Institute of Biomedical Sciences, Federal University of Alfenas, Rua Gabriel Monteiro da Silva, 700, 37130-000, Alfenas, MG, Brazil. Electronic address: marisaionta@gmail.com.
Marisa
M
Ionta
D000970:Antineoplastic Agents / Q000494:pharmacology*; D037821:Casearia; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism*; D045785:Diterpenes, Clerodane / Q000302:isolation & purification / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D015162:Micronucleus Tests; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry; D018515:Plant Leaves
D000970:Antineoplastic Agents; C530104:CCND1 protein, human; D045785:Diterpenes, Clerodane; D010936:Plant Extracts; C000614112:casearin D; D019938:Cyclin D1; D048049:Extracellular Signal-Regulated MAP Kinases
Casearia sylvestris; Casearins; Cell cycle arrest; Cyclin D1 expression; Hepatocellular carcinoma