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  • Title: T-17, a spirostanol saponin, inhibits p53-independent proliferation and p53-dependent migration of gastric cancer cells.
    Author: Xu J, Wang Y, Wang Z, Wang Y, He X.
    Journal: Steroids; 2021 Jun; 170():108828. PubMed ID: 33781788.
    Abstract:
    The p53 tumor suppressor gene contributes to a series of life processes of cells. Previously, we have shown that T-17, a spirostanol saponin extracted from Tupistra chinensis induces cell cycle arrest, apoptosis and autophagy in gastric cancer cells. The p53 is essential in the cell cycle arrest induced by T-17, however, the effect of p53 on T-17-induced apoptosis and autophagy is still unclear. Here, our study shows that T-17 has no difference in the sensitivity of gastric cancer cells with different p53 status. By transfecting p53 siRNA into AGS cells (p53 wild type cells) or wild-type p53 into KATO-III cells (p53 deficiency cells), T-17 was found to induce apoptosis and autophagy in gastric cancer cells in a p53-independent manner. Pre-treatment with N-acetylcysteine (NAC, a ROS scavenger) demonstrated that reactive oxygen species (ROS) mediated T-17-induced p53-independent apoptosis. Besides, T-17 induces apoptosis and autophagy in gastric cancer cells by decreasing the expression of HMGB1, also in a p53-independent manner. But when we detected the inhibitory effect of T-17 on gastric cancer cell migration, it was found that p53 is essential. These experimental results showed that T-17 induced apoptosis and autophagy in gastric cancer cells in a p53-independent manner, but inhibited the migration of gastric cancer cells in a p53-dependent manner. Our research indicates that T-17 is a potential candidate for gastric cancer and provides support for better utilization of Tupistra chinensis.
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