Differential Role of Apoptosis and Autophagy Associated with Anticancer Effect of Lupulone (Hop β-Acid) Derivatives on Prostate Cancer Cells

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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  • 27th of 59 in Chemistry, Medicinal

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Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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Differential Role of Apoptosis and Autophagy Associated with Anticancer Effect of Lupulone (Hop β-Acid) Derivatives on Prostate Cancer Cells



Anti-Cancer Agents in Medicinal Chemistry, 14(8): 1169-1178.

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.

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.




Keywords:

Apoptosis, autophagy, caspases, hop β-acids, lupulone, prostate cancer cells.



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Article Details

Volume: 14
Issue Number: 8
First Page: 1169
Last Page: 1178
Page Count: 10
DOI: 10.2174/1871520614666140623123006
Price: $58
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