A1E Induces Apoptosis via Targeting HPV E6/E7 Oncogenes and Intrinsic Pathways in Cervical Cancer Cells

초록

A1E is an extract from traditional Asian medicinalplants that has therapeutic activities against cancers, metabolicdisease, and other intractable conditions. However, its mechanismof action on cervical cancer has not been studied. In order toascertain if A1E would have pronounced anti-cervical cancereffect, cervical cancer cells were incubated with A1E and apoptosiswas detected by nuclear morphological changes, annexin V-FITC/PI staining, cell cycle analysis, western blotting, Reverse-transcriptionpolymerase chain reaction, and measurement of mitochondrialmembrane potential. Expression of human papiloma virus E6 andE7 oncogenes was down-regulated in A1E-treated cervical cancercells, while p53 and retinoblastoma protein levels were enhanced. A1E also perturbed cell cycle progression at sub-G1 and alteredcell cycle regulatory factors in SiHa cervical cancer cells. A1Eactivated apoptotic intrinsic pathway markers such as caspase-9,caspase-3 and poly ADP-ribose polymerase, and down-regulatedexpression of Bcl-2 and Bcl-xl. A1E induced mitochondrialmembrane potential collapse and cytochrome c release, andinhibited phosphatidylinositol 3-kinase (PI3K)/Akt, key factorsinvolved in cell survival signaling. Taken all these results, A1Einduced apoptosis via activation of the intrinsic pathway andinhibition of the PI3K/Akt survival-signaling pathway in SiHacervical cancer cells. In conclusion, A1E exerts anti-proliferativeaction growth inhibition on cervical cancer cells through apoptosiswhich demonstrates its anti-cervical cancer properties.

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