Rhabdastrellic acid-A inhibited PI3K/Akt pathway and induced apoptosis in human leukemia HL-60 cells.
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.
Guo
Jing-Feng
JF
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, 651 Dongfeng Road East, Guangzhou 510060, PR China.
Zhou
Jun-Min
JM
Zhang
Yong
Y
Deng
Rong
R
Liu
Jian-Nan
JN
Feng
Gong-Kan
GK
Liu
Zong-Chao
ZC
Xiao
Ding-Jun
DJ
Deng
Song-Zhi
SZ
Zhu
Xiao-Feng
XF
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D004249:DNA Damage; D015536:Down-Regulation; D004789:Enzyme Activation; D018922:HL-60 Cells; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects*; D014315:Triterpenes / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
C494826:BAX protein, human; D061945:Caspase Inhibitors; D009842:Oligopeptides; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D014315:Triterpenes; C108637:aspartyl-glutamyl-valyl-aspartal; D051028:bcl-2-Associated X Protein; C529429:rhabdastrellic acid A; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3