The microarray expression analysis identifies BAX as a mediator of beta-carotene effects on apoptosis.
Beta-carotene is a ubiquitous compound rich in foods. However, there are conflicting reports regarding its role in carcinogenesis. We performed a microarray expression analysis in normal [human umbilical vein endothelial cells (HUVECs)] and neoplastic (melanoma A375 and myelomonocytic leukemia U937) actively proliferating cells and found evidence that beta-carotene stimulated vital cellular functions in the former and suppressed them in the latter. These differential effects correlated with the expression of the proapoptotic BCL2-associated X protein (BAX), which was downregulated in HUVECs and upregulated in the two neoplastic cell lines. The quantitative expression analysis using real-time polymerase chain reaction largely confirmed the inhibition of B-cell CLL/lymphoma 2 (BCL2) pathway-mediated apoptosis in HUVECs and its activation in melanoma and leukemic cells. The assays for apoptosis, detecting DNA breaks and caspase activation, showed consistent proapoptotic and antiapoptotic effects in U937 and HUVEC lines, respectively. However, beta-carotene-induced expression changes of BAX and other BCL2 pathway genes did not lead to the predicted induction of apoptosis in the A375 cells.
Bodzioch
Marek
M
Department of Clinical Biochemistry, Collegium Medicum, Jagiellonian University, Krakow, Poland. mb22@mp.pl
Dembinska-Kiec
Aldona
A
Hartwich
Jadwiga
J
Lapicka-Bodzioch
Katarzyna
K
Banas
Agnieszka
A
Polus
Anna
A
Grzybowska
Joanna
J
Wybranska
Iwona
I
Dulinska
Joanna
J
Gil
Dorota
D
Laidler
Piotr
P
Placha
Wojciech
W
Zawada
Magdalena
M
Balana-Nowak
Agnieszka
A
Sacha
Tomasz
T
Kiec-Wilk
Beata
B
Skotnicki
Aleksander
A
Moehle
Christoph
C
Langmann
Thomas
T
Schmitz
Gerd
G
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects; D004357:Drug Synergism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D020287:In Situ Nick-End Labeling / Q000379:methods; D066298:In Vitro Techniques; D015479:Leukemia, Myelomonocytic, Acute / Q000378:metabolism*; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism*; D008954:Models, Biological; D040081:Protein Array Analysis / Q000379:methods; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism; D051028:bcl-2-Associated X Protein; D019207:beta Carotene / Q000494:pharmacology*
D000975:Antioxidants; C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019207:beta Carotene