Anti-proliferative effects of evodiamine on human thyroid cancer cell line ARO.
The incidence of thyroid cancer increases with age, and it is twice in women as common as in men. The undifferentiated thyroid cancer (UTC) is the most aggressive of all thyroid cancers. Unfortunately, there are almost no efficacious therapeutic modalities. It is important to develop some new effective therapies. Evodiamine is a chemical extracted from a kind of Chinese herb named Wu-Chu-Yu and has been demonstrated to be effective in preventing the growth of a variety of cancer cells. In the present study, the mechanism by which evodiamine inhibited the undifferentiated thyroid cancer cell line ARO was examined. Based on 3-(4,5-dimethylthiazol -2-yle)2,5-diphenyltetrazolium bromide (MTT) assay, cell proliferation rate was reduced dose-dependently by evodiamine, but not by rutaecarpine. According to the flow cytometric analysis, evodiamine treatment resulted in G2/M arrest and DNA fragmentation in ARO cells. The G2/M arrest was accompanied with an increase of the expression of cdc25C, cyclin B1, and cdc2-p161 protein, and it was also with a decrease of the expression of cdc2-p15. Furthermore, by using the TUNEL assay, evodiamine-induced apoptosis was observed at 48 h and extended to 72 h. Western blotting demonstrated that evodiamine treatment induced the activation of caspase-8, caspase-9, caspase-3, and the cleavage of poly ADP-ribose polymerase (PARP). These results suggested that evodiamine inhibited the growth of the ARO cells, arrested them at M phase, and induced apoptosis through caspases signaling.
Chen
Meng-Ching
MC
Department of Physiology, School of Medicine, National Yang-Ming University, Taipei City 11221, Taiwan, Republic of China.
Yu
Ching-Han
CH
Wang
Shyi-Wu
SW
Pu
Hsiao-Fung
HF
Kan
Shu-Fen
SF
Lin
Lie-Chwen
LC
Chi
Chin-Wen
CW
Ho
Lary Low-Tone
LL
Lee
Chen-Hsen
CH
Wang
Paulus S
PS
D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D032086:Evodia / Q000737:chemistry; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D026121:Indole Alkaloids / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D052999:Quinazolinones
D020169:Caspases; D018797:Cell Cycle Proteins; D026121:Indole Alkaloids; D010936:Plant Extracts; D011065:Poly(ADP-ribose) Polymerases; D011799:Quinazolines; C028632:rutecarpine; D052999:Quinazolinones; C049639:evodiamine