Treatment of PC-3 and DU145 prostate cancer cells by prenylflavonoids from hop (Humulus lupulus L.) induces a caspase-independent form of cell death.
Xanthohumol (X), isoxanthohumol (IX), 8-prenylnaringenin (8PN) and 6-prenylnaringenin (6PN), prenylflavonoids from hop (Humulus lupulus L.), were investigated for their cytotoxicity and the mechanism by which they exert cell death when incubated with prostate cancer cell lines PC-3 and DU145. All compounds induced cell death in the absence of caspase-3 activation and typical apoptotic morphological features. The general pan-caspase inhibitor zVAD-fmk could not protect this form of cell death. In addition, the formation of vacuoles was observed in PC-3 cells treated with IX and 6PN, and in DU145 treated with IX, 8PN and 6PN, which could suggest the induction of autophagy and consequent cell death. The results indicate that hop-derived prenylflavanones (IX, 8PN, 6PN), but not prenylchalcones (X) induce a caspase-independent form of cell death, suggested to be autophagy. Therefore, IX, 8PN and 6PN appear to be promising candidates for further investigation in prostate anticancer therapy.
Delmulle
L
L
Ghent University-UGent, Faculty of Pharmaceutical Sciences, Laboratory of Pharmacognosy and Phytochemistry, B-9000 Ghent, Belgium.
Vanden Berghe
T
T
Keukeleire
D De
DD
Vandenabeele
P
P
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D027582:Humulus / Q000737:chemistry*; D008297:Male; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011427:Propiophenones / Q000737:chemistry / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology
C521871:6-prenylnaringenin; C119737:8-prenylnaringenin; D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D044950:Flavanones; D005419:Flavonoids; D010936:Plant Extracts; D011427:Propiophenones; D044004:Xanthones; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C512910:isoxanthohumol; D053148:Caspase 3; D020169:Caspases; C104536:xanthohumol