Pyrrolidine dithiocarbamate inhibition of luteolin-induced apoptosis through up-regulated phosphorylation of akt and caspase-9 in human leukemia HL-60 cells

An Chin Cheng, Tzou Chi Huang, Ching Shu Lai, Jen Min Kuo, Ying Tang Huang, Chih Yu Lo, Chi Tang Ho, Min Hsiung Pan

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Previously, we observed that luteolin effectively inhibited cell growth and induced apoptosis in HL-60 cells. In that study, we also explored the modulatory effects and molecular mechanisms of pyrrolidine dithiocarbamate (PDTC) on the cytotoxicity of luteolin to HL-60 cells. In this study, we found that PDTC was able to inhibit luteolin-induced cell apoptosis in a dose-dependent manner. When HL-60 cells were treated with PDTC for 0.5 h before 60 μM luteolin treatment, the DNA ladder disappeared. Moreover, flow cytometry showed that PDTC had dose dependently decreased the percentage of apoptotic HL-60 cells and had not interfered with luteolin's ability to change the mitochondrial membrane potential or its ability to trigger the release of cytochrome cto cytosol. Detection by Western blotting, however, did show that PDTC had interfered with luteolin's ability to cleave poly(ADP-ribose)-" polymerase and DNA fragmentation of factor-45. Three hours after the PDTC-pretreated HL-60 cells were treated with 60 μM luteolin, the product cleaved from Akt started to appear. Therefore, not only was PDTC able to stop the apoptosis of HL-60 cells treated with luteolin, it was also found to increase phosphorylation of Akt and caspase-9. These results suggest that in the luteolin-induced apoptotic pathway, phosphorylation of procaspase-9 by survival signals might play an important role in the ultimate fate of HL-60 cells.

Original languageEnglish (US)
Pages (from-to)4215-4221
Number of pages7
JournalJournal of agricultural and food chemistry
Volume54
Issue number12
DOIs
StatePublished - Jun 14 2006

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Agricultural and Biological Sciences

Keywords

  • Akt
  • Apoptosis
  • Caspase-9
  • Luteolin
  • PDTC (pyrrolidine dithiocarbamate)

Fingerprint

Dive into the research topics of 'Pyrrolidine dithiocarbamate inhibition of luteolin-induced apoptosis through up-regulated phosphorylation of akt and caspase-9 in human leukemia HL-60 cells'. Together they form a unique fingerprint.

Cite this