Combination of tumor necrosis factor alpha and interferon alpha induces apoptotic cell death through a c-myc-dependent pathway in p53 mutant H226br non-small-cell lung cancer cell line

Yasuo Yasuoka, Yoshio Naomoto, Tomoki Yamatsuji, Munenori Takaoka, Masashi Kimura, Hirokazu Uetsuka, Nagahide Matsubara, Toshiyoshi Fujiwara, Mehmet Gunduz, Noriaki Tanaka, Minoru Haisa

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

We investigated the role of wild-type p53 and c-myc activity in apoptosis induced by a combination of natural human tumor necrosis factor alpha (TNF-α) and natural human interferon alpha (IFN-α). Studies were performed with two human non-small-cell lung cancer cell lines, H226b, which has wild-type p53, and H226br, which has a mutant p53. The combination of IFN-α and TNF-α significantly inhibited cell growth and induced apoptotic cell death of both H226b and H226br, compared with IFN-α or TNF-α alone. Treatment with one or both cytokines did not affect the expression level of p53 in both cell lines. These results suggest that the combination of IFN-α/TNF-α induces apoptotic cell death through a p53- independent pathway. The c-myc oncogene is known to be involved in apoptosis induced by TNF. Antisense c-myc oligonucleotides have been reported to modulate cell growth or apoptosis in several cell lines. Antisense oligodeoxynucleotides were added to the culture of H226br cells before the addition of IFN-α/TNF-α. Antisense c-myc inhibited IFN-α/TNF-α cytotoxicity and apoptotic cell death. In conclusion, this study provides support for the speculation that TNF-α/IFN-α induce apoptosis through a c-myc-dependent pathway rather than a p53-dependent pathway.

Original languageEnglish
Pages (from-to)214-222
Number of pages9
JournalExperimental Cell Research
Volume271
Issue number2
DOIs
Publication statusPublished - Dec 10 2001

Fingerprint

Interferon-alpha
Non-Small Cell Lung Carcinoma
Cell Death
Tumor Necrosis Factor-alpha
Cell Line
Apoptosis
myc Genes
Oligodeoxyribonucleotides
Growth
Oligonucleotides
Cell Culture Techniques
Cytokines

Keywords

  • Antisense oligonucleotides
  • Apoptosis
  • p53
  • TNF-α/IFN-α

ASJC Scopus subject areas

  • Cell Biology

Cite this

Combination of tumor necrosis factor alpha and interferon alpha induces apoptotic cell death through a c-myc-dependent pathway in p53 mutant H226br non-small-cell lung cancer cell line. / Yasuoka, Yasuo; Naomoto, Yoshio; Yamatsuji, Tomoki; Takaoka, Munenori; Kimura, Masashi; Uetsuka, Hirokazu; Matsubara, Nagahide; Fujiwara, Toshiyoshi; Gunduz, Mehmet; Tanaka, Noriaki; Haisa, Minoru.

In: Experimental Cell Research, Vol. 271, No. 2, 10.12.2001, p. 214-222.

Research output: Contribution to journalArticle

Yasuoka, Yasuo ; Naomoto, Yoshio ; Yamatsuji, Tomoki ; Takaoka, Munenori ; Kimura, Masashi ; Uetsuka, Hirokazu ; Matsubara, Nagahide ; Fujiwara, Toshiyoshi ; Gunduz, Mehmet ; Tanaka, Noriaki ; Haisa, Minoru. / Combination of tumor necrosis factor alpha and interferon alpha induces apoptotic cell death through a c-myc-dependent pathway in p53 mutant H226br non-small-cell lung cancer cell line. In: Experimental Cell Research. 2001 ; Vol. 271, No. 2. pp. 214-222.
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