Evodiamine, a constituent of Evodiae Fructus, induces anti-proliferating effects in tumor cells.
We found that evodiamine, a major alkaloidal component of Evodiae Fructus (Goshuyu in Japan), inhibited proliferation of several tumor cell lines, but had less effect on human peripheral blood mononuclear cells (PBMC). We used human cervical cancer cells, HeLa, as a model to elucidate the molecular mechanisms of evodiamine-induced tumor cell death. The results showed that evodiamine induced oligonucleosomal fragmentation of DNA in HeLa cells and increased the activity of caspase-3, but not that of caspase-1, in vitro. Both evodiamine-induced DNA fragmentation and caspase-3 activity were effectively inhibited by a caspase-3 inhibitor, z-DEVD-fmk (z-Asp-Glu-Val-Asp-fmk). In addition, evodiamine increased the expression of the apoptosis inducer Bax, but decreased the expression of the apoptosis suppressor Bcl-2 in mitochondria. Taken together, our data indicated that evodiamine alters the balance of Bcl-2 and Bax gene expression and induces apoptosis through the caspase pathway in HeLa cells.
Fei
Xiao Fang
XF
College of Life Sciences, Jilin University, Changchun 130012, China.
Wang
Ben Xiang
BX
Li
Tei Jin
TJ
Tashiro
Shin-ichi
S
Minami
Mutsuhiko
M
Xing
De Jun
DJ
Ikejima
Takashi
T
D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D032086:Evodia / Q000737:chemistry*; D005354:Fibrosarcoma / Q000473:pathology; D005472:Fluorouracil / Q000494:pharmacology; D005663:Furans / Q000737:chemistry / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects; D006367:HeLa Cells / Q000187:drug effects / Q000201:enzymology; D022781:Hepatocytes / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D026121:Indole Alkaloids; D007948:Leukemia, Monocytic, Acute / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008545:Melanoma / Q000473:pathology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011915:Rats, Inbred BUF; D012510:Sarcoma 180 / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000201:enzymology; D051028:bcl-2-Associated X Protein; D052999:Quinazolinones
D000470:Alkaloids; D000590:Amino Acid Chloromethyl Ketones; D000972:Antineoplastic Agents, Phytogenic; D053148:Caspase 3; D020169:Caspases; D015853:Cysteine Proteinase Inhibitors; D003609:Dactinomycin; D005472:Fluorouracil; D005663:Furans; D006576:Heterocyclic Compounds, 4 or More Rings; D026121:Indole Alkaloids; D009363:Neoplasm Proteins; D009842:Oligopeptides; D010936:Plant Extracts; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011799:Quinazolines; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C494827:Bax protein, mouse; C494828:Bax protein, rat; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C473746:evodine; C028632:rutecarpine; D052999:Quinazolinones; C049639:evodiamine; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat