Hop proanthocyanidins induce apoptosis, protein carbonylation, and cytoskeleton disorganization in human colorectal adenocarcinoma cells via reactive oxygen species.
Proanthocyanidins (PCs) have been shown to suppress the growth of diverse human cancer cells and are considered as promising additions to the arsenal of chemopreventive phytochemicals. An oligomeric mixture of PCs from hops (Humulus lupulus) significantly decreased cell viability of human colon cancer HT-29 cells in a dose-dependent manner. Hop PCs, at 50 or 100 microg/ml, exhibited apoptosis-inducing properties as shown by the increase in caspase-3 activity. Increased levels of intracellular reactive oxygen species (ROS) was accompanied by an augmented accumulation of protein carbonyls. Mass spectrometry-based proteomic analysis in combination with 2-alkenal-specific immunochemical detection identified beta-actin and protein disulfide isomerase as major putative targets of acrolein adduction. Incubation of HT-29 cells with hop PCs resulted in morphological changes that indicated disruption of the actin cytoskeleton. PC-mediated hydrogen peroxide (H2O2) formation in the cell culture media was also quantified; but, the measured H2O2 levels would not explain the observed changes in the oxidative modifications of actin. These findings suggest new modes of action for proanthocyandins as anticarcinogenic agents in human colon cancer cells, namely, promotion of protein oxidative modifications and cytoskeleton derangement.
Chung
Woon-Gye
WG
Department of Chemistry, Oregon State University, Corvallis, OR 97331, United States.
Miranda
Cristobal L
CL
Stevens
Jan F
JF
Maier
Claudia S
CS
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000595:Amino Acid Sequence; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003599:Cytoskeleton / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D027582:Humulus / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008969:Molecular Sequence Data; D044945:Proanthocyanidins / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism*
D016588:Anticarcinogenic Agents; D044945:Proanthocyanidins; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D005978:Glutathione