Rare sugar D-allose induces programmed cell death in hormone refractory prostate cancer cells.
Development of effective agents for treatment of hormone-refractory prostate cancer (HRPC) has become a national medical priority. D-Allose is a monosaccharide (C-3 epimer of glucose) distributed rarely in nature; because of its scarcity and cost, the biological effect has hardly been studied. In the present study, we demonstrated the inhibitory action of D-allose on proliferation of human HRPC cell lines, DU145 and PC-3 in a dose- and time-dependent manner, while human normal prostate epithelial (NPE) cell line, PrEC showed no remarkable effect. In vitro treatment of D-allose resulted in the alteration of Bcl-2/Bax ratio in favor of apoptosis (programmed cell death, PCD) in both the HRPC cell lines, which was associated with the lowering of mitochondrial transmembrane potential (Deltapsi(m)) and the release of cytochrome C (cyt C), the cleavage of caspase 3 and poly (ADP-ribose) polymerase (PARP), and the elevation of calcium concentration in cytosol ([Ca(2+)](c)). D-Allose also induced G1 phase arrest of the cell cycle in DU145 cell line. This study for the first time suggested the antiproliferative effect of D-allose through induction of PCD in HRPC cell lines, which could be due to the modulation of mitochondria mediated intrinsic apoptotic pathway.
Naha
Nibedita
N
Division of Life Science, Applied Life Science (Brain Korea 21 and EB-NCRC), Gyeongsang National University, Jinju 660-701, South Korea.
Lee
Hae Young
HY
Jo
Mi Ja
MJ
Chung
Bong Chul
BC
Kim
Sung Hoon
SH
Kim
Myeong Ok
MO
D000728:Androgens / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D020013:Calcium Signaling / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D016193:G1 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008954:Models, Biological; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D000728:Androgens; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C002055:allose; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D005947:Glucose