Gemcitabine induces poly (ADP-Ribose) polymerase-1 (PARP-1) degradation through autophagy in pancreatic cancer

Yufeng Wang, Yasuhiro Kuramitsu, Kazuhiro Tokuda, Byron Baron, Takao Kitagawa, Junko Akada, Shin Ichiro Maehara, Yoshihiko Maehara, Kazuyuki Nakamura

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Poly (ADP-ribose) polymerase-1 (PARP-1) and autophagy play increasingly important roles in DNA damage repair and cell death. Gemcitabine (GEM) remains the first-line chemotherapeutic drug for pancreatic cancer (PC). However, little is known about the relationship between PARP-1 expression and autophagy in response to GEM. Here we demonstrate that GEM induces DNA-damage response and degradation of mono-ADP ribosylated PARP-1 through the autophagy pathway in PC cells, which is rescued by inhibiting autophagy. Hypoxia and serum starvation inhibit autophagic activity due to abrogated GEM-induced mono-ADP-ribosylated PARP-1 degradation. Activation of extracellular regulated protein kinases (ERK) induced by serum starvation shows differences in intracellular localization as well as modulation of autophagy and PARP-1 degradation in GEM-sensitive KLM1 and -resistant KLM1-R cells. Our study has revealed a novel role of autophagy in PARP-1 degradation in response to GEM, and the different impacts of MEK/ERK signaling pathway on autophagy between GEM-sensitive and -resistant PC cells.

Original languageEnglish
Article numbere109076
JournalPloS one
Volume9
Issue number10
DOIs
Publication statusPublished - Oct 1 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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