Effect of human noxa on irinotecan-induced apoptosis in human gastric carcinoma cell lines.
OBJECTIVE
A protein BH3-only member bcl-2 family, Noxa is a proapoptotic mediator for p53-induced apoptosis. We analyzed the effect of Noxa on p53-induced apoptotic gastric carcinoma cell lines.


METHODS
The expressions of human Noxa (hNoxa) mRNA on human gastric carcinoma cell lines were assessed with RT-PCR. Further, hNoxa antisense and sense S-oligodeoxynucleotide (ODN) were used to analyze the effect of hNoxa on p53-induced apoptotic gastric carcinoma cell lines.


RESULTS
Various levels of hNoxa mRNA expression were detected in all gastric cell lines. MKN45 that has wild-type p53 showed severe inhibition by irinotecan compared with MKN28, which has mutated p53. Cell growth under hNoxa antisense S-ODN treatment did not differ from that under sense S-ODN treatment in MKN28. On the other hand, the suppression of cell growth in MKN45 decreased with hNoxa antisense S-ODN treatment as compared to hNoxa sense S-ODN treatment. MKN45 cells exhibited DNA fragmentation clearly after 24 hr of 3 mM hNoxa sense S-ODN treatment. The DNA fragmentation in MKN45 was inhibited by hNoxa antisense S-ODN treatment.


CONCLUSIONS
It seems that hNoxa plays an important role in induction of apoptosis on p53 wild type gastric carcinoma cell lines.
Sasaki
Takamitsu
T
Department of Oncological Pathology, Nara Medical University Cancer Center, Kashihara, Nara, Japan.
Sasahira
Tomonori
T
Shimura
Hideo
H
Ikeda
Seiyo
S
Kuniyasu
Hiroki
H
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D000077146:Irinotecan; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D013274:Stomach Neoplasms / Q000473:pathology*
D000972:Antineoplastic Agents, Phytogenic; C498702:PMAIP1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D000077146:Irinotecan; D002166:Camptothecin