Rhabdastrellic acid-A inhibited PI3K/Akt pathway and induced apoptosis in human leukemia HL-60 cells.

Abstract	Increasing evidence suggests that aberrant activation of PI3K/Akt is involved in many human cancers, and that inhibition of the PI3K/Akt pathway might be a promising strategy for cancer treatment. Our investigation indicates that Rhabdastrellic acid-A, an isomalabaricane triterpenoid isolated from the sponge, Rhabdastrella globostellata, inhibits proliferation of HL-60 cells with an IC(50) value of 0.68mug/ml, and induces apoptosis. Rhabdastrellic acid-A also induces cleavage of the death substrate poly (ADP-ribose) polymerase (PARP) and caspase-3. Pretreatment of HL-60 cells with the caspase-3 specific inhibitor, DEVD-CHO, prevents Rhabdastrellic acid-A-induced DNA fragmentation and PARP cleavage. Activated PI3K and Akt significantly decreases after treatment with Rhabdastrellic acid-A in HL-60 cells. Expression levels of protein bcl-2, bax remain unchanged in response to Rhabdastrellic acid-A treatment in HL-60 cells. These results suggest that Rhabdastrellic acid-A inhibits PI3K/Akt pathway and induces caspase-3 dependent-apoptosis in HL-60 human leukemia cells.
Authors	Jing-Feng Guo, Jun-Min Zhou, Yong Zhang, Rong Deng, Jian-Nan Liu, Gong-Kan Feng, Zong-Chao Liu, Ding-Jun Xiao, Song-Zhi Deng, Xiao-Feng Zhu
Journal	Cell biology international (Cell Biol Int) Vol. 32 Issue 1 Pg. 48-54 (Jan 2008) ISSN: 1065-6995 [Print] England
PMID	17920303 (Publication Type: Journal Article)
Chemical References	BAX protein, human Caspase Inhibitors Oligopeptides Phosphoinositide-3 Kinase Inhibitors Proto-Oncogene Proteins c-bcl-2 Triterpenes aspartyl-glutamyl-valyl-aspartal bcl-2-Associated X Protein rhabdastrellic acid A Proto-Oncogene Proteins c-akt Caspase 3
Topics	Apoptosis (drug effects) Caspase 3 (metabolism) Caspase Inhibitors DNA Damage Down-Regulation Enzyme Activation HL-60 Cells Humans Oligopeptides (pharmacology) Phosphoinositide-3 Kinase Inhibitors Proto-Oncogene Proteins c-akt (antagonists & inhibitors) Proto-Oncogene Proteins c-bcl-2 (biosynthesis) Signal Transduction (drug effects) Triterpenes (pharmacology) bcl-2-Associated X Protein (biosynthesis)

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