Apigenin induces apoptosis in human leukemia cells and exhibits anti-leukemic activity In Vivo

Amit Budhraja, Ning Gao, Zhuo Zhang, Young Ok Son, Senping Cheng, Xin Wang, Songze Ding, Andrew Hitron, Gang Chen, Jia Luo, Xianglin Shi

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

In this study, we investigated the functional role of Akt and c-jun-NH2-kinase (JNK) signaling cascades in apigenin-induced apoptosis in U937 human leukemia cells and anti-leukemic activity of apigenin in vivo. Apigenin induced apoptosis by inactivation of Akt with a concomitant activation of JNK, Mcl-1 and Bcl-2 downregulation, cytochrome c release from mitochondria, and activation of caspases. Constitutively active myristolated Akt prevented apigenin-induced JNK, caspase activation, and apoptosis. Conversely, LY294002 and a dominant-negative construct of Akt potentiated apigenin-induced apoptosis in leukemia cells. Interruption of the JNK pathway showed marked reduction in apigenin-induced caspase activation and apoptosis in leukemia cells. Furthermore, in vivo administration of apigenin resulted in attenuation of tumor growth inU937 xenografts accompanied by inactivation of Akt and activation of JNK. Attenuation of tumor growth in U937 xenografts by apigenin raises the possibility that apigenin may have clinical implications and can be further tested for incorporating in leukemia treatment regimens.

Original languageEnglish
Pages (from-to)132-142
Number of pages11
JournalMolecular Cancer Therapeutics
Volume11
Issue number1
DOIs
StatePublished - Jan 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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