Induction of apoptosis by yomogin in human promyelocytic leukemic HL-60 cells.
Yomogin is an active compound isolated from Artemisia princep, a traditional Oriental medicinal herb, which has been shown to inhibit tumor cell proliferation. In this study, we investigated the effects of yomogin on the cytotoxicity, induction of apoptosis, and putative pathways of its actions in human promyelocytic leukemia cells. Yomogin-treated HL-60 cells displayed several features of apoptosis, including DNA fragmentation, formation of DNA ladders in agarose gel electrophoresis, and externalization of annexin-V targeted phosphatidylserine residues. We observed that yomogin caused activation of caspase-8, caspase-9, and caspase-3. A general caspase inhibitor (z-VAD-fmk), caspase-8 inhibitor (z-IETD-fmk) and caspase-3 inhibitor (z-DEVD-fmk), almost completely suppressed the yomogin-induced DNA fragmentation. We further demonstrated that yomogin induced Bid cleavage, mitochondrial translocation of Bax from the cytosol, and cytochrome c release from mitochondria in a caspase-8-dependent manner. Taken together, our data indicate that yomogin is a potent inducer of apoptosis and facilitates its activity via caspase-8 activation, Bid cleavage, Bax translocation to mitochondria, and subsequent release of cytochrome c into the cytoplasm, providing a potential mechanism for the anticancer activity of yomogin.
Jeong
Seoung-Hee
SH
College of Pharmacy, Kyung Hee University, Hoegi-dong, Seoul, Korea.
Koo
Sung-Ja
SJ
Ha
Joo-Hun
JH
Ryu
Shi-Yong
SY
Park
Hee-Juhn
HJ
Lee
Kyung-Tae
KT
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D019306:Artemisia; D049109:Cell Proliferation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045787:Sesquiterpenes, Eudesmane
D010936:Plant Extracts; D012717:Sesquiterpenes; D045787:Sesquiterpenes, Eudesmane; C117320:yomogin