Anti-proliferative and apoptotic effects of celecoxib on human chronic myeloid leukemia in vitro

J. Subhashini, S. V.K. Mahipal, P. Reddanna

Research output: Contribution to journalArticle

Abstract

Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is the only non-steroidal anti-inflammatory drug so far which has been approved by the FDA for adjuvant treatment of patients with familial adenomatous polyposis. The molecular mechanism responsible for the anti-cancer effects of celecoxib is not fully understood. There is little data on the potential role of COX-2 in lymphoma pathogenesis. In view of the reported induction of apoptosis in cancer cells by cyclooxygenase-2 inhibitors, the present study is undertaken to test the effect of celecoxib on human chronic myeloid leukemia cell line, K562 and other hematopoietic cancer cell lines like Jurkat (human T lymphocytes), HL60 (human promyelocytic leukemia) and U937 (human macrophage). Treatment of these cells with celecoxib (10-100 μM) dose-dependently, reduced cell growth with arrest of the cell cycle at G0/G1 phase and induction of apoptosis. Further mechanism of apoptosis induction was elucidated in detail in K562 cell line. Apoptosis was mediated by release of cytochrome c into the cytoplasm and cleavage of poly (ADP-ribose) polymerase-1 (PARP-1). This was followed by DNA fragmentation. The level of anti-apoptotic protein Bcl-2 was decreased without any change in the pro-apoptotic Bax. Celecoxib also inhibited NF-kB activation. Celecoxib thus potentiates apoptosis as shown by MTT assay, cytochrome c leakage, PARP cleavage, DNA fragmentation, Bcl-2 downregulation and possibly by inhibiting NF-kB activation.

Original languageEnglish (US)
Pages (from-to)31-43
Number of pages13
JournalCancer Letters
Volume224
Issue number1
DOIs
StatePublished - Jun 16 2005

Keywords

  • Apoptosis
  • Bcl-2
  • Celecoxib
  • Chronic myelogenous leukemia
  • Cytochrome c
  • NF-kB
  • PARP

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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