Kaempferol induces apoptosis in two different cell lines via Akt inactivation, bax and SIRT3 activation, and mitochondrial dysfunction

Gabriella Marfe, Marco Tafani, Manuela Indelicato, Paola Sinibaldi-Salimei, Valentina Reali, Bruna Pucci, Massimo Fini, Matteo Antonio Russo

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Kaempferol (3,4′,5,7-tetrahydroxyflavone) is a flavonoid with anti- and pro-oxidant activity present in various natural sources. Kaempferol has been shown to posses anticancer properties through the induction of the apoptotic program. Here we report that treatment of the chronic myelogenous leukemia cell line K562 and promyelocitic human leukemia U937 with 50 mM kaempferol resulted in an increase of the antioxidant enzymes Mn and Cu/Zn superoxide dismutase (SOD). Kaempferol treatment induced apoptosis by decreasing the expression of Bcl-2 and increasing the expressions of Bax. There were also induction of mitochondrial release of cytochrome c into cytosol and significant activation of caspase-3, and -9 with PARP cleavage. Kaempferol treatment increased the expression and the mitochondria localization of the NAD-dependent deacetylase SIRT3. K562 cells stably overexpressing SIRT3 were more sensitive to kaempferol, whereas SIRT3 silencing did not increase the resistance of K562 cells to kaempferol. Inhibition of PI3K and de-phosphorylation of Akt at Ser473 and Thr308 was also observed after treating both K562 and U937 cells with kaempferol. In conclusion our study shows that the oxidative stress induced by kaempferol in K562 and U937 cell lines causes the inactivation of Akt and the activation of the mitochondrial phase of the apoptotic program with an increase of Bax and SIRT3, decrease of Bcl-2, release of cytochrome c, caspase-3 activation, and cell death.

Original languageEnglish
Pages (from-to)643-650
Number of pages8
JournalJournal of Cellular Biochemistry
Volume106
Issue number4
DOIs
Publication statusPublished - Mar 1 2009

Fingerprint

Chemical activation
Cells
Apoptosis
Cell Line
K562 Cells
U937 Cells
Cytochromes c
Caspase 3
kaempferol
Phosphorylation
Mitochondria
Oxidative stress
Caspase 9
Cell death
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Phosphatidylinositol 3-Kinases
Flavonoids
Oxidants
NAD
Cytosol

Keywords

  • Apoptosis
  • Bax
  • Bcl-2
  • Kaempferol
  • Sirtuins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Kaempferol induces apoptosis in two different cell lines via Akt inactivation, bax and SIRT3 activation, and mitochondrial dysfunction. / Marfe, Gabriella; Tafani, Marco; Indelicato, Manuela; Sinibaldi-Salimei, Paola; Reali, Valentina; Pucci, Bruna; Fini, Massimo; Russo, Matteo Antonio.

In: Journal of Cellular Biochemistry, Vol. 106, No. 4, 01.03.2009, p. 643-650.

Research output: Contribution to journalArticle

Marfe, Gabriella ; Tafani, Marco ; Indelicato, Manuela ; Sinibaldi-Salimei, Paola ; Reali, Valentina ; Pucci, Bruna ; Fini, Massimo ; Russo, Matteo Antonio. / Kaempferol induces apoptosis in two different cell lines via Akt inactivation, bax and SIRT3 activation, and mitochondrial dysfunction. In: Journal of Cellular Biochemistry. 2009 ; Vol. 106, No. 4. pp. 643-650.
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