Chloramphenicol-induced mitochondrial stress increases p21 expression and prevents cell apoptosis through a p21-dependent pathway

Ching Hao Li, Su Liang Tzeng, Yu Wen Cheng, Jaw Jou Kang

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)


Pretreatment of HepG2 and H1299 cells with chloramphenicol rendered the cells resistant to mitomycin-induced apoptosis. Both mitomycin-induced caspase 3 activity and PARP activation were also inhibited. The mitochondrial DNA-encoded Cox I protein, but not nuclear-encoded proteins, was down-regulated in chloramphenicol-treated cells. Cellular levels of the p21waf1/cip1 protein and p21waf1/cip1 mRNA were increased through a p53-independent pathway, possibly because of the stabilization of p21 waf1/cip1 mRNA in chloramphenicol-treated cells. The p21 waf1/cip1 was redistributed from the perinuclear region to the cytoplasm and co-localized with mitochondrial marker protein. Several morphological changes and activation of the senescence-associated biomarker, SA β-galactosidase, were observed in these cells. Both p21waf1/cip1 antisense and small interfering RNA could restore apoptotic-associated caspase 3 activity, PARP activation, and sensitivity to mitomycin-induced apoptosis. Similar effects were seen with other antibiotics that inhibit mitochondrial translation, including minocycline, doxycycline, and clindamycin. These findings suggested that mitochondrial stress causes resistance to apoptosis through a p21-dependent pathway.

Original languageEnglish
Pages (from-to)26193-26199
Number of pages7
JournalJournal of Biological Chemistry
Issue number28
Publication statusPublished - Jul 15 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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