Kaempferide induces apoptosis in cervical cancer by attenuating the HPV oncoproteins, E6 and E7

Abstract

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=142 SRC="FIGDIR/small/541414v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@1e1cf7forg.highwire.dtl.DTLVardef@1fdc5dforg.highwire.dtl.DTLVardef@1c9baa6org.highwire.dtl.DTLVardef@fcf063_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO A schematic diagram depicting the anti-cancer potential of kaempferide against cervical cancer and its probable mechanism of action. C_FIG Despite the advancement in HPV prevention strategies, cervical cancer is a leading cause of cancer death in women worldwide. The anticancer potential of kaempferide, which was derived from Chromolaena odorata, was previously revealed in our in-vitro study. The current investigation aims to confirm the therapeutic efficacy of the molecule against cervical cancer, in-vitro and in-vivo. In NOD-SCID mice with HeLa Luc+ xenografts, kaempferide significantly increases ROS production resulting in a drastic decrease in the luc activity and growth of cervical tumours. It also exhibits down-regulation of oncoproteins E6, E7 and MDM2 and concurrent up-regulation of p53, p21 and pRb. The degradation of phospho-pRb, along with a strong expression of cleaved PARP, TUNEL positivity and a significant decrease in PCNA expression, confirms apoptotic mode of cell death in the treated tissues. Taken together, our study reveals the antioncogenic potential of kaempferide, which regulates oncoproteins and tumor suppressors accordingly. This is the first report depicting kaempferide as an inhibitor of HPV oncoproteins and hence as a candidate drug molecule against cervical cancer.