Title:Differential Role of Apoptosis and Autophagy Associated with Anticancer Effect of Lupulone (Hop β-Acid) Derivatives on Prostate Cancer Cells
VOLUME: 14 ISSUE: 8
Author(s):Petros X.E. Mouratidis, Kay W. Colston, Nicoletta Charolidi and Grisha Pirianov
Affiliation:Division of Clinical Sciences, St. George's University of London, London SW17 0RE, UK.
Keywords:Apoptosis, autophagy, caspases, hop β-acids, lupulone, prostate cancer cells.
Abstract:Lupulone, a β-acid derived from hop extracts has been shown to exhibit cytotoxic activity against cancer cells. In this study we
investigated the functional role of different modes of cell death that mediate anticancer effect of lupulone derivatives in prostate cancer
cells. ELISA, immunoblotting and siRNA approaches were utilised to study cell death, expression of proteins of interest and their
functional activities. We found that the anticancer effect of lupulone derivatives on prostate cancer cells is associated with induction of
apoptosis and autophagy as determined by increases of DNA fragmentation and LC3I/ LC3II conversion respectively. Inhibition of
apoptosis using a pan-caspase inhibitor resulted in increased levels of autophagy. Following screening of proteins associated with
autophagy we found that Atg4β expression was increased in prostate cancer cells after treatment with lupulone. Transfection of cells with
siRNA against Atg4β resulted in increased levels of apoptosis in prostate cancer cells. Treatment of prostate cancer cells with lupulone
derivatives initiated two modes of cell death: apoptosis as a killing pathway and autophagy as a protection against cell death. Further
studies are required to investigate the regulation of Atg4β activity in lupulone derivatives-induced negative crosstalk between apoptosis
and autophagy.
