Ursolic Acid Promotes Apoptosis of SGC-7901 Gastric Cancer Cells through ROCK/PTEN Mediated Mitochondrial Translocation of Cofilin-1

Abstract

Ursolic acid, extracted from the traditional Chinese medicine bearberry, can induce apoptosis of gastric cancer cells. However, its pro-apoptotic mechanism still needs further investigation. More and more evidence demonstrates that mitochondrial translocation of cofilin-1 appears necessary for the regulation of apoptosis. Here, we report that ursolic acid (UA) potently induces the apoptosis of gastric cancer SGC-7901 cells. Further mechanistic studies revealed that the ROCK1/PTEN signaling pathway plays a critical role in UA-mediated mitochondrial translocation of cofilin-1 and apoptosis. These findings imply that induction of apoptosis by ursolic acid stems primarily from the activation of ROCK1 and PTEN, resulting in the translocation of cofilin-1 from cytoplasm to mitochondria, release of cytochrome c, activation of caspase-3 and caspase-9, and finally inducing apoptosis of gastric cancer SGC-7901 cells.

Anti-cancer effect of ursolic acid activates apoptosis through ROCK/PTEN mediated mitochondrial translocation of cofilin-1 in prostate cancer

“…In addition, the corresponding mechanism of action of cofilin-1 may be associated with the promotion of cyclase-associated protein 1 (25). Furthermore, when cofilin-1 protein translocates into the mitochondria from the cytoplasm, it activates cytochrome c release and activation of the caspase cascade, indirectly inducing cell apoptosis (25). The results of the present study demonstrated that ursolic acid significantly inhibited cofilin-1 protein expression in DU145 cells.…”

“…It has been reported that cofilin-1 protein will translocate into the mitochondria from the cytoplasm; subsequently, cytochrome c will be released from mitochondria and combine with Apaf-1 to activate caspase-9, so that the caspase cascade will be activated and lead to apoptosis (19). In addition, the corresponding mechanism of action of cofilin-1 may be associated with the promotion of cyclase-associated protein 1 (25). Furthermore, when cofilin-1 protein translocates into the mitochondria from the cytoplasm, it activates cytochrome c release and activation of the caspase cascade, indirectly inducing cell apoptosis (25).…”

“…Achiwa et al (29) suggested that ursolic acid induces apoptosis in SNG-II endometrial cancer cells through reduction of mitochondrial cytochrome c release. Li et al (25) reported that ursolic acid induced apoptosis of SGC-7901 gastric cancer cells through cytochrome c.…”

“…The present study observed that ursolic acid significantly downregulated the ROCK/PTEN signal transduction pathway in DU145 cells. Li et al (25) reported that ursolic acid induced apoptosis of SGC-7901 gastric cancer cells through suppression of ROCK/PTEN.…”

“…A current focus of cancer research concerns the development of medicines to promote cell apoptosis. Cytochrome c is an essential component of the respiratory chain and has a significant role in the oxidation and reduction of cells (25). Utilized as a cell respiration-activating enzyme in the clinic, cytochrome c is an ancillary drug used to treat cancer (26).…”