Polymethoxyflavones activate Ca 2+-dependent apoptotic targets in adipocytes

Igor N. Sergeev, Shiming Li, Chi Tang Ho, Nancy E. Rawson, Slavik Dushenkov

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Induction of apoptosis is an emerging strategy for the prevention and treatment of obesity because removal of adipocytes via apoptosis will result in reducing body fat and may help to maintain a long-lasting weight loss. Our previous studies have shown that a sustained increase in intracellular Ca 2+ triggers apoptosis in various cell types via activation of Ca 2+-dependent proteases and that the apoptosis-inducing effect of polymethoxyflavones (PMFs) in cancer cells is mediated through Ca 2+ signaling. This paper reports that PMFs induce apoptosis in mature mouse 3T3-L1 adipocytes via activation of Ca 2+-dependent calpain and Ca 2+/calpain-dependent caspase-12. Treatment of adipocytes with PMFs evoked, in a concentration- and time-dependent fashion, sustained increase in the basal level of intracellular Ca 2+. The increase in Ca 2+ was associated with induction of apoptosis and activation of μ-calpain and caspase-12. Apoptosis-inducing activity of hydroxylated PMFs was significantly higher than that of the corresponding nonhydroxylated compounds. These results demonstrate that the apoptotic molecular targets activated by PMFs in adipocytes are Ca 2+-dependent calpain and caspase-12. The findings obtained provide rationale for evaluating the role of PMFs in the prevention and treatment of obesity.

Original languageEnglish (US)
Pages (from-to)5771-5776
Number of pages6
JournalJournal of agricultural and food chemistry
Volume57
Issue number13
DOIs
StatePublished - Jul 8 2009

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

Keywords

  • 3T3-L1 cells
  • Adipocytes
  • Apoptosis
  • Calpain
  • Caspase-12
  • Intracellular Ca
  • Obesity
  • Polymethoxyflavones

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