Effects of artemisinin and its derivatives on growth inhibition and apoptosis of oral cancer cells.
BACKGROUND
Artemisinin is of special biological interest because of its outstanding antimalarial activity. Recently, it was reported that artemisinin has antitumor activity. Its derivatives, artesunate, arteether, and artemeter, also have antitumor activity against melanoma, breast, ovarian, prostate, CNS, and renal cancer cell lines. Recently, monomer, dimer, and trimer derivatives were synthesized from deoxoartemisinin, and the dimers and the trimers were found to have much more potent antitumor activity than the monomers.


METHODS
We evaluated the antitumor activity of artemisinin and its various derivatives (dihydroartemisinin, dihydroartemisinin 12-benzoate, 12-(2'-hydroxyethyl) deoxoartemisinin, 12-(2'-ethylthio) deoxoartemisinin dimer, deoxoartemisinin trimer) in comparison with paclitaxel (Taxol), 5-fluorouracil (5-FU), cisplatin in vitro.


RESULTS
In this study, the deoxoartemisinin trimer had the most potent antitumor effect (IC(50) = 6.0 microM), even better than paclitaxel (IC(50) = 13.1 microM), on oral cancer cell line (YD-10B). In addition, it induced apoptosis through a caspase-3-dependent mechanism.


CONCLUSIONS
The deoxoartemisinin trimer was found to have greater antitumor effect on tumor cells than other commonly used chemotherapeutic drugs, such as 5-FU, cisplatin, and paclitaxel. Furthermore, the ability of artemisinin and its derivatives to induce apoptosis highlights their potential as chemotherapeutic agents, for many anticancer drugs achieve their antitumor effects by inducing apoptosis in tumor cells.
Nam
Woong
W
Department of Oral and Maxillofacial Surgery, College of Dentistry, Yonsei University, Seoul, Korea.
Tak
Jungae
J
Ryu
Ju-Kyoung
JK
Jung
Mankil
M
Yook
Jong-In
JI
Kim
Hyung-Jun
HJ
Cha
In-Ho
IH
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D019306:Artemisia; D037621:Artemisinins / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009062:Mouth Neoplasms / Q000473:pathology*; D012717:Sesquiterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D037621:Artemisinins; D012717:Sesquiterpenes; C031327:artemisinin