Induction of apoptosis by d-limonene is mediated by a caspase-dependent mitochondrial death pathway in human leukemia cells.
Using K562 and HL60 cell lines, we have investigated the anti-tumoral activity of d-limonene, a monocyclic monoterpene, in human leukemia cells. Apoptosis was evaluated by Hoechst staining and by the annexin V/propidium iodide binding assay. d-Limonene induced apoptosis in a dose- and time-dependent manner in both cell lines. Our findings and data, demonstrating an increase in Bax protein expression, the release of cytochrome c from mitochondria, and an increase in caspase-9 and cleaved caspase-3, but not caspase-8, after the treatment of d-limonene, all suggest that the mitochondrial death pathway is primarily involved in the development of d-limonene-induced apoptosis.
Ji
Jun
J
Department of Central Laboratory, Dalian Municipal Central Hospital, Dalian, China.
Zhang
Li
L
Wu
Yuan-Yuan
YY
Zhu
Xiao-Yu
XY
Lv
Su-Qing
SQ
Sun
Xi-Zuo
XZ
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002470:Cell Survival; D053138:Cyclohexenes / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology*; D000077222:Limonene; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D013729:Terpenes / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D053138:Cyclohexenes; D013729:Terpenes; D045304:Cytochromes c; D000077222:Limonene; D020169:Caspases