Evodiamine induces caspase-dependent apoptosis and S phase arrest in human colon lovo cells.
Evodiamine, one of the major bioactive components derived from Wu-Chu-Yu, a long-standing Chinese herb, was reported to possess anticancer activity. In this study, we investigated the in-vitro and in-vivo anticancer effects of evodiamine on human colon lovo cells and their potential mechanisms. The 3-(4, 5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the in-vitro proliferation of lovo cells was inhibited by evodiamine of various concentrations. Flow cytometry showed a time-dependent increase in the percentage of apoptotic cells and cells arrested in the S phase after treatment with 60 micromol/l evodiamine. Western blot indicated that evodiamine treatment decreased the expression of procaspase-8, procaspase-9, and procaspase-3 in lovo cells, accompanied by the activation of caspase-8, caspase-9, and caspase-3. However, the translocation of apoptosis-inducing factor and endonuclease G was not affected by evodiamine. Moreover, western blot assay also suggested that evodiamine-induced S phase arrest in lovo cells was associated with a marked decrease in the protein expression of cyclinA, cyclinA-dependent kinase 2, and cdc25c. In-vivo antineoplastic characteristics of evodiamine were examined in a human colon carcinoma lovo xenograft model and results showed that evodiamine increased the number of TUNEL-positive cells accompanied by the downregulated expression of procaspase-8, procaspase-9, and procaspase-3. In conclusion, these findings indicated that evodiamine could inhibit the in-vitro and in-vivo proliferation of human colon lovo cells by inducing caspase-dependent apoptosis and S phase arrest.
Zhang
Chun
C
Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing, China.
Fan
Xia
X
Xu
Xiang
X
Yang
Xue
X
Wang
Xi
X
Liang
Hua-Ping
HP
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D004706:Endodeoxyribonucleases / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010936:Plant Extracts / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D016196:S Phase; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D011799:Quinazolines; D051028:bcl-2-Associated X Protein; C049639:evodiamine; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D020169:Caspases