title: Eudesmol isomers induce caspase-mediated apoptosis in human hepatocellular carcinoma HepG2 cells.
abstract: Eudesmols are naturally occurring sesquiterpenoid alcohols that present cytotoxic effect to cancer cells. Herein, all eudesmol isomers displayed cytotoxicity to different tumour cell lines. α-Eudesmol showed IC₅₀ values ranging from 5.38 ± 1.10 to 10.60 ± 1.33 μg/mL for B16-F10 and K562 cell lines, β-eudesmol showed IC₅₀ values ranging from 16.51 ± 1.21 to 24.57 ± 2.75 μg/mL for B16-F10 and HepG2 cell lines, and γ-eudesmol showed IC₅₀ values ranging from 8.86 ± 1.27 to 15.15 ± 1.06 μg/mL for B16-F10 and K562 cell lines, respectively. In addition, in this work, we studied the mechanisms of cytotoxic action of eudesmol isomers (α-, β- and γ-eudesmol) in human hepatocellular carcinoma HepG2 cells. After 24-hr incubation, HepG2 cells treated with eudesmol isomers presented typical hallmarks of apoptosis, as observed by morphological analysis in cells stained with haematoxylin-eosin and acridine orange/ethidium bromide. None of eudesmol isomers caused membrane disruption at any concentration tested. Moreover, eudesmol isomers induced loss of mitochondrial membrane potential and an increase in caspase-3 activation in HepG2 cells, suggesting the induction of caspase-mediated apoptotic cell death. In conclusion, the eudesmol isomers herein investigated are able to reduce cell proliferation and to induce tumour cell death by caspase-mediated apoptosis pathways.
authors.affiliation: Department of Physiology, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Diogo S
authors.initials: DS
authors.lastname: Bomfim
authors.forename: Rosana P C
authors.initials: RP
authors.lastname: Ferraz
authors.forename: Nanashara C
authors.initials: NC
authors.lastname: Carvalho
authors.forename: Milena B P
authors.initials: MB
authors.lastname: Soares
authors.forename: Maria L B
authors.initials: ML
authors.lastname: Pinheiro
authors.forename: Emmanoel V
authors.initials: EV
authors.lastname: Costa
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Bezerra
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D045787:Sesquiterpenes, Eudesmane / Q000494:pharmacology*
chemical_list: D045787:Sesquiterpenes, Eudesmane; C499668:gamma-eudesmol; C051082:beta-eudesmol; C118684:alpha-eudesmol; C505407:CASP3 protein, human; D053148:Caspase 3