Tephrosin (Tep)

Tephrosin, a natural rotenoid which has potent antitumor activities, induced internalization of EGFR and ErbB2, and thereby induced degradation of the receptors. Treatment of HT-29 cells with tephrosin inhibited both the ligand-induced and constitutive phosphorylation of EGFR, ErbB2 and ErbB3, and concomitantly suppressed the activation of the downstream signaling molecules such as Akt and Erk1/2 mitogen-activated protein kinase (MAPK). Tephrosin caused internalization of EGFR and ErbB2 into vehicles, which resulted in degradation of the receptors. This degradation was blocked by the lysosomal inhibitor, chloroquine. Tephrosin did not induce the proteolytic processing of caspase-3 and poly(ADP-ribose) polymerase (PARP), but did nuclear translocation of apoptosis-inducing factor (AIF), suggesting that tephrosin may induce caspase-independent apoptosis.