Resveratrol-induced transcriptional up-regulation of ASMase (SMPD1) of human leukemia and cancer cells

Naoki Mizutani, Yukari Omori, Yoshiyuki Kawamoto, Sayaka Sobue, Masatoshi Ichihara, Motoshi Suzuki, Mamoru Kyogashima, Mitsuhiro Nakamura, Keiko Tamiya-Koizumi, Yoshinori Nozawa, Takashi Murate

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Resveratrol (RSV) is a plant-derived phytoalexin present in plants, whose pleiotropic effects for health benefits have been previously reported. Its anti-cancer activity is among the current topics for novel cancer treatment. Here, effects of RSV on cell proliferation and the sphingolipid metabolism of K562, a human leukemia cell line, were analyzed. Some experiments were also performed in HCT116, a human colon cancer cell line. RSV inhibited cell proliferation of both cell lines. Increased cellular ceramide and decreased sphingomyelin and S1P by RSV were observed in RSV-treated K562 cells. Further analysis revealed that acid sphingomyelinase mRNA and enzyme activity levels were increased by RSV. Desipramine, a functional ASMase inhibitor, prevented RSV-induced ceramide increase. RSV increased ATF3, EGR1, EGR3 proteins and phosphorylated c-Jun and FOXO3. However, co-transfection using these transcription factor expression vectors and ASMase promoter reporter vector revealed positive effects of EGR1 and EGR3 but not others. Electrophoresis mobility shift assay (EMSA) and Chromatin immunoprecipitation (ChIP) assay demonstrated the direct binding of EGR1/3 transcription factors with ASMase 5′-promoter. These results indicate that increased EGR1/3 and ASMase expression play an important role in cellular ceramide increase by RSV treatment.

Original languageEnglish
Pages (from-to)851-856
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume470
Issue number4
DOIs
Publication statusPublished - 19-02-2016
Externally publishedYes

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Mizutani, N., Omori, Y., Kawamoto, Y., Sobue, S., Ichihara, M., Suzuki, M., Kyogashima, M., Nakamura, M., Tamiya-Koizumi, K., Nozawa, Y., & Murate, T. (2016). Resveratrol-induced transcriptional up-regulation of ASMase (SMPD1) of human leukemia and cancer cells. Biochemical and Biophysical Research Communications, 470(4), 851-856. https://doi.org/10.1016/j.bbrc.2016.01.134