Citrus aurantium L. exhibits apoptotic effects on U937 human leukemia             cells partly through inhibition of Akt.
Citrus fruits have been used as edible fruits and a traditional medicine             since ancient times. In particular, the peels of immature citrus fruits are frequently             prescribed in concert with other support herbs for many types of disease including             cancer. We investigated the anti-proliferative activity of the peels of Citrus             aurantium L. along with their effects on apoptosis. We prepared crude methanol             extracts of the peels of Citrus aurantium L. (CMEs) and performed experiments             using U937 human leukemia cells. The growth of U937 cells was inhibited by CME             treatment in a dose-dependent manner, and CME induced caspase-dependent apoptosis.             CME inhibited the expression of XIAP and Bcl-xL which are anti-apoptotic proteins.             CME inhibited Akt activity in a dose-dependent manner. The apoptotic activity             of CME was significantly attenuated by Akt augmentation. In conclusion, this study             suggested that CME should induce caspase-dependent apoptosis at least in part             through Akt inhibition, providing evidence that CMEs have anticancer activity             on human leukemia cells.
Department of Biochemistry, Dongeui University College of Oriental                     Medicine and Department of Biomaterial Control (BK21 Program), Dongeui                     University Graduate School, Busan 614-052, Republic of Korea.
Min Ho
MH
Han
Won Sup
WS
Lee
Jing Nan
JN
Lu
Gonsup
G
Kim
Jin Myung
JM
Jung
Chung Ho
CH
Ryu
Gi-Young
GY
Kim
Hye Jin
HJ
Hwang
Taeg Kyu
TK
Kwon
Yung Hyun
YH
Choi
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002957:Citrus / Q000737:chemistry*; D004789:Enzyme Activation; D005638:Fruit / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D007938:Leukemia; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020298:U937 Cells; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D010936:Plant Extracts; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases