MAPK activation is necessary to the apoptotic death of KB cells induced by the essential oil isolated from Artemisia iwayomogi.
OBJECTIVE
Artemisia iwayomogi is a perennial small herbal plant that has long been used as a chemopreventive agent in traditional Korean medicine. Previously, the purified essential oil was isolated from Artemisia iwayomogi, herein named AIEO, and found to contain the active components responsible for the chemopreventive potential of the herb.


METHODS
This study examined whether or not AIEO has potential chemopreventative effects against cancer using the human oral epidermoid carcinoma cell line, KB cells. The possible mechanism of AIEO-induced apoptosis was also examined.


RESULTS
The results showed that AIEO induces the apoptotic death of KB cells, which is mediated by mitogen-activated protein kinases (MAPKs). In addition, AIEO not only induced an imbalance between the mitochondrial Bcl-2 and Bax levels with the concomitant release of Cytochrome c into the cytosol but also induced the activation of caspases and the cleavage of PARP. This induction was significantly suppressed by MAPK inhibitors. Moreover, pretreating the cells with each of the caspase or MAPK-specific inhibitors apparently inhibited AIEO-induced cytotoxicity of KB cells.


CONCLUSIONS
These results strongly suggest that AIEO might have cancer chemopreventive and therapeutic potential, which is closely related to its ability to activate the MAPK-mediated signaling pathways with the subsequent induction of a mitochondria- and caspase-dependent mechanism.
Cha
Jeong-Dan
JD
Oral Cancer Research Institute, College of Dentistry, Yonsei University, Seoul 120-749, Republic of Korea.
Jeong
Mi-Ran
MR
Kim
Hye-Young
HY
Lee
Jeong-Chae
JC
Lee
Kyung-Yeol
KY
D017209:Apoptosis / Q000187:drug effects*; D019306:Artemisia / Q000737:chemistry*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000503:physiopathology; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007624:KB Cells; D020935:MAP Kinase Signaling System / Q000187:drug effects; D055670:Medicine, Korean Traditional; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009822:Oils, Volatile / Q000302:isolation & purification / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000378:metabolism
D009822:Oils, Volatile; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases