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.