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Effect of human noxa on irinotecan-induced apoptosis in human gastric carcinoma cell lines

Takamitsu Sasaki1, Tomonori Sasahira, Hideo Shimura

  • 1Department of Oncological Pathology, Nara Medical University Cancer Center, Kashihara, Nara, Japan.

Hepato-Gastroenterology
|May 18, 2004
PubMed
Abstract

Insights

The proapoptotic protein Noxa is crucial for p53-induced apoptosis in gastric cancer. Inhibiting Noxa with antisense oligonucleotides reduced apoptosis in wild-type p53 gastric cancer cells.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Biology

Background:

  • Noxa, a BH3-only protein in the BCL-2 family, mediates p53-induced apoptosis.
  • Gastric carcinoma cell lines were investigated for their response to Noxa modulation.

Purpose of the Study:

  • To analyze the role of Noxa in p53-induced apoptosis in gastric carcinoma.
  • To investigate the impact of Noxa modulation on gastric cancer cell apoptosis.

Main Methods:

  • RT-PCR was used to assess human Noxa (hNoxa) mRNA expression in gastric cell lines.
  • hNoxa antisense and sense S-oligodeoxynucleotides (ODN) were employed to study Noxa's effect on apoptosis.

Main Results:

  • hNoxa mRNA was expressed in all tested gastric cell lines.
  • MKN45 (wild-type p53) showed greater inhibition by irinotecan than MKN28 (mutated p53).
  • hNoxa antisense ODN treatment reduced growth suppression and DNA fragmentation in MKN45 cells, indicating inhibited apoptosis.

Conclusions:

  • hNoxa appears to play a significant role in inducing apoptosis in gastric carcinoma cell lines with wild-type p53.

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