Abstract 1006: Celastrol modulated Taz and induced cell apoptosis in vitro

Abstract

Abstract Celastrol is derived from the Chinese medicinal plant Tripterygium wilfordii, which has attracted great attention for its potent anticancer effects. Celastrol has been found to inhibit the proliferation, induce apoptosis, and suppress invasion/migration and angiogenesis both in vitro and in vivo. In our current study, we treated the HEK293 cells with the Celastrol(0.75μM) for 24h and found that Celastrol could reduce the expression of TAZ in HEK293 cells. To better evaluate the effect of TAZ on HEK293 cells, cell growth curve and colony formation assay were performed. HEK293/TAZ and HEK293/control cells were plated at a density of 50 cells/mm2 in triplicate for 5 days and HEK293/TAZ and HEK293/control cells were seeded into six-well plates of 500 cells/well for two weeks. The result showed that HEK293/TAZ grew obviously faster and could form more colonies than HEK293/control cells. To further address the effect of TAZ in vivo, equal numbers(1.5×106) of HEK293/TAZ and HEK293/control cells were injected bilateral subcutaneously into nude mice. The mice were sacrificed 40 days after injection. We found that the latency of tumor formation in nude mice injected with HEK293/TAZ cells was shorter than the tumor injected with HEK293/control cells. Furthermore, HEK293/TAZ cells could lead to a larger tumor size compared to the HEK293/control cells. Our data indicated that the overexpression of TAZ could significantly promote cell proliferation in vitro and in vivo. Furthermore, after HEK293/TAZ and HEK293/control cells were treated with Celastrol(0.75μM) for 24h, the data showed that the less PARP cleavage was definitely observed in HEK293/TAZ cells than HEK293/control cells by Western blotting. Moreover, 18.9% of HEK293/TAZ cells were TUNEL-positive, compared with 83.2% of HEK293/control cells after Celastrol treatment(0.75μM, 24h). Our data indicated that overexpression of TAZ could overcome partially the cell apoptosis induced by Celastrol in vitro. In summary, our finding prompts that Celastrol could suppress growth of tumor cells through the modulation of TAZ, and the mechanism how TAZ plays its function needs to be further explored. Citation Format: Shuren Wang. Celastrol modulated Taz and induced cell apoptosis in vitro. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1006. doi:10.1158/1538-7445.AM2015-1006