Actinomycin D induces apoptosis and inhibits growth of pancreatic cancer cells

Jörg Kleeff, Marko Kornmann, Harneet Sawhney, Murray Korc

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Pancreatic cancer cells are usually resistant to apoptosis induced by cytotoxic drugs, by activation of surface receptors such as Fas and TNF receptor or by serum or growth factor withdrawal. Actinomycin D (actD) is an inhibitor of RNA synthesis and acts as a potent inducer of apoptosis in several cell lines. In the present study, we investigated the effects of actD on PANC-I pancreatic cancer cells. ActD caused apoptosis in PANC-I cells in a dose-dependent manner, as determined by cell growth assays, DNA laddering and TUNEL assays. Induction of apoptosis correlated with activation of the JNK/SAPK pathway and increased expression of Bax but not Bad or p53. PANC-I cells were completely resistant to Fas antibody and TNF-α. In contrast, TRAIL decreased the growth of PANC-I cells by 22%. Low concentrations of actD (10 ng/ml) enhanced the cytotoxic effects of all 3 cytokines. EGF, FGF-2 and IGF-I did not protect PANC-I cells from actD-mediated apoptosis. ActD (10 ng/ml) also inhibited the growth of CAPAN-I and T3M4 pancreatic cancer cells but not MiaPaCa-2 cells. Our observations suggest that actD may act via JNK/SAPK and Bax to promote apoptosis in PANC-I cells and that it may inhibit the growth of other pancreatic cancer cell lines. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)399-407
Number of pages9
JournalInternational Journal of Cancer
Volume89
Issue number2
StatePublished - 2000
Externally publishedYes

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Dactinomycin
Pancreatic Neoplasms
Apoptosis
Growth
Nucleic Acid Synthesis Inhibitors
CD95 Antigens
Cell Line
MAP Kinase Signaling System
Tumor Necrosis Factor Receptors
In Situ Nick-End Labeling
Fibroblast Growth Factor 2
Insulin-Like Growth Factor I
Epidermal Growth Factor
Intercellular Signaling Peptides and Proteins
Cytokines
Antibodies
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kleeff, J., Kornmann, M., Sawhney, H., & Korc, M. (2000). Actinomycin D induces apoptosis and inhibits growth of pancreatic cancer cells. International Journal of Cancer, 89(2), 399-407.

Actinomycin D induces apoptosis and inhibits growth of pancreatic cancer cells. / Kleeff, Jörg; Kornmann, Marko; Sawhney, Harneet; Korc, Murray.

In: International Journal of Cancer, Vol. 89, No. 2, 2000, p. 399-407.

Research output: Contribution to journalArticle

Kleeff, J, Kornmann, M, Sawhney, H & Korc, M 2000, 'Actinomycin D induces apoptosis and inhibits growth of pancreatic cancer cells', International Journal of Cancer, vol. 89, no. 2, pp. 399-407.
Kleeff, Jörg ; Kornmann, Marko ; Sawhney, Harneet ; Korc, Murray. / Actinomycin D induces apoptosis and inhibits growth of pancreatic cancer cells. In: International Journal of Cancer. 2000 ; Vol. 89, No. 2. pp. 399-407.
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