PA-42 誘導人類口腔癌鱗狀細胞（HSC-3）細胞凋亡與抑制細胞轉移之分子機轉

Abstract

The oral cancer is the most incident cancer, with the place rate rising fast from 10th forward 6th most common cause of cancer death in past fifteen years in Taiwan. PA-42 is an anticancer active compound and isolated from a Chinese medicine herb, physalis angulata. Physalis angulata has been reported to exhibit anti-tumor effect in several human cancers such as leukemia, lung, colon, cervix, hepatoma and melanomas cancers. In our preliminary studies, we first investigated the influence of PA-42 in human oral squamous carcinoma cancer (OSCC) cell lines HSC-3. We evaluate the chemopreventive role of cancer of PA-42 in vitro by studying the regulation of proliferation, cell cycle, and apoptosis with dose- and time- dependent manner by MTT assay, flow cytometry, nuclear DAPI stain assay, comet assay, and DNA fragmentation assay. In the results, the data shown that PA-42 has exhibited effective cells growth inhibition in HSC-3 cells. Low dose of PA-42 induced DNA damage and then led to undergo G2/M phase arrest, with an increase in p53 and wee1 and a decrease in cdc2 and Cyclin A/B1 and protein. PA-42 induced the Ca2+ production release and a decrease in the mitochondrial membrane potential in HSC-3 cells. PA-42 induced apoptosis by releasing AIF、Bax and Bcl-2 from mitochondria, and cleavage caspase-3 and then caused DNA fragmentation. PA-42 also increased the expression of Fas in HSC-3 cells. The conclusion of the results is that PA-42 induced apoptosis through both the intrinsic and extrinsic pathways in HSC-3 cells. In our study, PA-42 has revealed that the migration and invasion of HSC-3 cells was suppressed by wound healing assay, transwell migration assay, and matrigel invasion assay. PA-42 has also suppressed MMP-3 and GRB2 expressions with western blot and reversed cytoskeleton from mesenchymal-like to epithelial-like with confocal image in HSC-3 cells. The conclusion of the results is that PA-42 suppressed metastasis in HSC-3 cells. These results indicate that PA-42 induced apoptosis and suppressed metastasis in HSC-3 cells. PA-42 is a novel candidate agent for the chemoprevention of human oral squamous cancer in the future.