Figure 6
From: Targeting the actin cytoskeleton: selective antitumor action via trapping PKCɛ
Chondramide affects tumor growth in vivo via actin polymerization-induced abrogation of PKCɛ signaling. (a) Tumor volume of female SCID mice harboring a MDA-MB-231 tumor in their flank that were either treated with solvent control (DMSO) or 0.75 mg/kg/day Chondramide. Significance analysis was performed using Student’s t-test with *P<0.05, **P<0.01. (b) Statistical analysis of TUNEL-stained paraffin sections. Six fields per tumor were visualized and counted. (c) Cryosections of tumors were stained for actin (red), PKCɛ (green) and nuclei (blue). Scale bar indicates 50 μm. Representative images of a control and Chondramide-treated tumor borders are shown. Inserts in the merged images show a magnification of a few single cells. Bars represent the mean ±S.E.M. of three independent experiments performed in triplicates, *P<0.05 (one-way ANOVA, Bonferroni). (d) Cartoon illustrating the mode of action of ChA. Physiological state: PKCɛ activity leads to stabilization of the Hexokinase II/VDAC interaction and phosphorylation of Bad, both of which prevent efflux of cytochrome C and support survival of cancer cells. Chondramide A treatment: ChA leads to actin hyperpolymerization and impairment of PKCɛ signaling, thereby to destabilization of the Hexokinase II/VDAC complex and dephosphorylation of Bad, resulting in cytochrome C release and induction of apoptosis
