Akt
kinase is a critical component of the PI3K/Akt signaling pathway, which is frequently over expressed in human
cancers including breast. Therapeutic regimens for inhibiting
breast cancer with aberrant Akt activity are essential. Here, we evaluated antitumor effect of a marine bacteria derived
lipopeptide '
Iturin A' on human
breast cancer in vitro and in vivo through disrupting Akt pathway. Proliferation of MDA-MB-231 and MCF-7
breast cancer cells were significantly inhibited by
Iturin A and it induced apoptosis as confirmed by increased Sub G1 populations, DNA fragmentation, morphological changes and western blot analysis. Furthermore,
Iturin A inhibited
EGF induced Akt phosphorylation (Ser473 and Thr308) and its downstream targets GSK3β and FoxO3a.
Iturin A inactivated MAPK as well as Akt
kinase leading to the translocation of FoxO3a to the nucleus. Gene silencing of Akt in MDA-MB-231 and MCF-7 cells reduced the sensitivity of
cancer cells to
Iturin A. Interestingly, overexpression of Akt with Akt plasmid in
cancer cells caused highly susceptible to induce apoptosis by
Iturin A treatment. In a xenograft model,
Iturin A inhibited
tumor growth with reduced expressions of Ki-67, CD-31, P-Akt, P-GSK3β, P-FoxO3a and P-MAPK. Collectively, these findings imply that
Iturin A has potential anticancer effect on
breast cancer.