beta-carotene at high concentrations induces apoptosis by enhancing oxy-radical production in human adenocarcinoma cells.
This is the first report demonstrating a relationship between apoptosis induction and changes of intracellular redox potential in the growth-inhibitory effects of high concentrations of beta-carotene in a tumor cell line. beta-Carotene inhibited the growth of human WiDr colon adenocarcinoma cells in a dose- and time-dependent manner, induced apoptosis, and blocked Bcl-2 expression. These effects were accompanied by an enhanced production of intracellular reactive oxygen species (ROS). The addition of the antioxidant alpha-tocopherol blocked both the pro-oxidant and the growth-inhibitory effects of the carotenoid. These findings suggest that beta-carotene may act as an inductor of apoptosis by its pro-oxidant properties.
Palozza
P
P
Institute of General Pathology, Catholic University, Rome, Italy. ibipg@rm.unicatt.it
Calviello
G
G
Serini
S
S
Maggiano
N
N
Lanza
P
P
Ranelletti
F O
FO
Bartoli
G M
GM
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals / Q000378:metabolism; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D016877:Oxidants / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000378:metabolism / Q000494:pharmacology; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019207:beta Carotene / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
D000975:Antioxidants; C494811:BCL2L1 protein, human; D005609:Free Radicals; D006131:Growth Inhibitors; D016877:Oxidants; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019207:beta Carotene; D014810:Vitamin E