Ursolic Acid Accelerates Taxol-induced Apoptosis via Activation of Bid-Mitochondria-Cyto c Signaling Pathway

Taxol triggers apoptosis in a variety of cancer cell types and activated NF-
_K
B is regarded as a main reason to cancer cells resistance to Taxol-induced apoptosis. Ursolic acid, a natural component, can inhibit activation of NF-
_K
B in many apoptosis stimulus, such as TNF, cispatin. In order to find synergistic effect between Taxol and ursolic acid, plasmid pFRET-Bid, pE-GFP-Cyt-c, and pDsRed-Mit were used to dynamically monitor cleavage of Bid, and cytochrome c release from mitochondria in Taxol alone and combination treatment of Taxol and ursolic acid. In Taxol alone, Bid was not cleaved and cytochrome c was not released from mitochondria in ASTC-a-1 cells, however, cleavage of Bid and release of cytochrome c from mitochondria were observed in combination treatment of Taxol and ursolic acid, so we predicted that activation of Bid-Mitochodria-Cyto c signaling pathway might contribute to the enhancement of Taxol-induced apoptosis with ursolic acid during combination treatment. Furthermore, Taxol-induced apoptosis in ASTC-a-1 cells may be mainly dependent on intrinsic apoptosis pathway, and mitochondria may mediate apoptosis speed.