Orphan nuclear receptor Nur77 translocates to mitochondria in the early phase of apoptosis induced by synthetic chenodeoxycholic acid derivatives in human stomach cancer cell line SNU-1.
Apoptosis-inducing activity of synthetic CDCA derivatives, HS-1199 and HS-1200, on gastric cancer cell line SNU-1 cells was explored. CDCA derivatives demonstrated various apoptosis hallmarks, such as mitochondrial changes, activation of caspase, DNA fragmentation, and nuclear condensation. Importantly, the orphan receptor Nur77 (TR3) was shown to translocate from the nucleus to mitochondria at the early time points after CDCA derivatives treatment. These data support the theory that CDCA derivatives-induced apoptosis of SNU-1 gastric cancer cell lines is mediated by mitochondria and caspase, and, at least in part, by Nur77.
Jeong
Jin Hee
JH
Department of Anatomy and Cell Biology (BK21 program), Dong-A University College of Medicine and Institute of Science, Busan, South Korea.
Park
Joo-Sung
JS
Moon
Bongkyung
B
Kim
Min Chan
MC
Kim
Jae-Kon
JK
Lee
Sungeun
S
Suh
Hongsuk
H
Kim
Nam Deuk
ND
Kim
Jong-Min
JM
Park
Young Chul
YC
Yoo
Young Hyun
YH
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D021381:Protein Transport / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D013274:Stomach Neoplasms; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D002635:Chenodeoxycholic Acid