[Evodiamine induces A375-S2 cell death through two different pathways].
OBJECTIVE
To study the mechanism of evodiamine-induced cell death of A375-S2.


METHODS
The changes in cell morphology were observed by invert microscopy and Hoechst 33258 staining. DNA fragmentation was assayed by agarose gel electrophoresis. The effects of evodiamine on apoptosis and cell cycle were studied by flow cytometric analysis.


RESULTS
Evodiamine was shown to markedly inhibit the growth of A375-S2 cells in dose- and time-dependent manners. At the early stage, evodiamine activated caspase cascades, which unexpectedly did not induce typical DNA fragmentation. At later stage, caspase inhibitors failed to block A375-S2 cell death induced by evodiamine. Evodiamine-induced cell death was shown to be not directly associated with cell cycle arrest.


CONCLUSIONS
At the early stage, evodiamine initiates caspase-dependent and a typical apoptosis pathway in A375-S2 cells, but later it induces cell death through caspase-independent pathway which might be necrosis.
Zhang
Ying
Y
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China.
Wu
Li-jun
LJ
Tashiro
Shin-ichi
S
Onodera
Satoshi
S
Ikejima
Takashi
T
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D053938:DNA Fragmentation / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D032086:Evodia / Q000737:chemistry; D006801:Humans; D008545:Melanoma / Q000201:enzymology / Q000473:pathology; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D011799:Quinazolines / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D061945:Caspase Inhibitors; D010936:Plant Extracts; D011799:Quinazolines; C049639:evodiamine; D020169:Caspases