Selective suppression of cervical cancer Hela cells by 2-O-β-d-glucopyranosyl-l-ascorbic acid isolated from the fruit of Lycium barbarum L.

Lycium barbarum fruit has been used as a Chinese traditional medicine and dietary supplement for centuries. 2-O-beta-d-Glucopyranosyl-l-ascorbic acid (AA-2 beta G), a novel stable vitamin C analog, is one of the main biologically active components of the fruit. In this report, we investigated the cytotoxic and antiproliferative effect of AA-2 beta G against cancer cells in vitro and identified the proteins with significantly differential expression in the cervical cancer cells (Hela) cultured in the presence of AA-2 beta G proteomic analysis. Our results demonstrated that the cytotoxic and antiproliferative activity of AA-2 beta G on cancer cell lines were in a cell type-, time-, and dose-dependent manner. Similar to vitamin C, the AA-2 beta G selectively induced cell death repressed the proliferation of Hela cells by the mechanism of cell apoptosis and cell cycle arrest induced by AA-2 beta G through a mechanism of stabilizing p53 protein. However, the biological activity of inhibition of cell proliferation in other malignant cancer cell lines or primary cells were varied, as demonstrated by either moderate inhibition or slight promotion following treatment with AA-2 beta G. Comparative analysis of the proteomic profiles and immunoblot analysis identified 15 proteins associated with repressing cell apoptosis and/or stimulating cell proliferation in Hela cells that were downregulated in the presence of AA-2 beta G or vitamin C. These data indicate that a mechanism of the AA-2 beta G and vitamin C mediated antitumor activity by downregulating the expression of proteins involved in cell apoptosis and proliferation and consequently inducing Hela cell apoptosis and cell cycle arrest, suggesting that AA-2 beta G and vitamin C may share a similar mechanism of inducing Hela cell apoptosis. These results also suggest that the L. barbarum fruit may be a potential dietary supplement and anticancer agent aimed at the prevention and treatment of cervical cancer.