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. 2016 Oct;12(4):2880-2885.
doi: 10.3892/ol.2016.5015. Epub 2016 Aug 16.

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

Wen-Tao Gai  1 , Da-Peng Yu  2 , Xin-Sheng Wang  3 , Pei-Tao Wang  3
Affiliations

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

Wen-Tao Gai et al. Oncol Lett. 2016 Oct.

Abstract

Ursolic acid is a type of pentacyclic triterpene compound with multiple pharmacological activities including cancer resistance, protection from liver injury, antisepsis, anti-inflammation and antiviral activity. The present study aimed to investigate the anticancer effect of ursolic acid. Ursolic acid activates cell apoptosis and its pro-apoptotic mechanism remains to be fully elucidated. Cell Counting kit-8 assays, flow cytometric analysis and analysis of caspase-3 and caspase-9 activity were used to estimate the anticancer effect of ursolic acid on DU145 prostate cancer cells. The protein expression of cytochrome c, rho-associated protein kinase (ROCK), phosphatase and tensin homolog (PTEN) and cofilin-1 were examined using western blot analysis. In the present study, ursolic acid significantly suppressed cell growth and induced apoptosis, as well as increasing caspase-3 and caspase-9 activities of DU145 cells. Furthermore, cytoplasmic and mitochondrial cytochrome c protein expression was significantly activated and suppressed, respectively, by ursolic acid. Ursolic acid significantly suppressed the ROCK/PTEN signaling pathway and inhibited cofilin-1 protein expression in DU145 cells. The results of the present study indicate that the anticancer effect of ursolic acid activates cell apoptosis through ROCK/PTEN mediated mitochondrial translocation of cofilin-1 in prostate cancer.

Keywords: cofilin-1; cytochrome c; prostate cancer; rho-associated protein kinase/phosphatase and tensin homolog; ursolic acid.

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Figures

Figure 1.
Figure 1.
Chemical structure of ursolic acid.
Figure 2.
Figure 2.
Anticancer effect of ursolic acid treatment on growth in prostate cancer cells. **P<0.01 compared with 0 µM ursolic acid group.
Figure 3.
Figure 3.
Anticancer effect of ursolic acid treatment on apoptosis in prostate cancer cells. **P<0.01 compared with 0 µM ursolic acid group.
Figure 4.
Figure 4.
Anticancer effect of ursolic acid treatment on (A) caspase-3 and (B) caspase-9 activity in prostate cancer cells. **P<0.01 compared with 0 µM ursolic acid group.
Figure 5.
Figure 5.
Anticancer effect of ursolic acid treatment on cytochrome c protein expression in prostate cancer cells. Anticancer effect of ursolic acid treatment on cytochrome c protein expression assessed (A) by western blotting assays and (B) quantification of cytochrome c protein expression in prostate cancer cells. **P<0.01 compared with 0 µM ursolic acid group.
Figure 6.
Figure 6.
Anticancer effect of ursolic acid treatment on ROCK protein expression in prostate cancer. Anticancer effect of ursolic acid treatment on ROCK protein expression assessed (A) by western blotting assays and (B) quantification of ROCK protein expression in prostate cancer cells. **P<0.01 compared with 0 µM ursolic acid group. ROCK, rho-associated protein kinase.
Figure 7.
Figure 7.
Anticancer effect of ursolic acid treatment on PTEN protein expression in prostate cancer. Anticancer effect of ursolic acid treatment on PTEN protein expression assessed (A) by western blotting assays and (B) quantification of PTEN protein expression in prostate cancer cells. **P<0.01 compared with 0 µM ursolic acid group. PTEN, phosphatase and tensin homolog.
Figure 8.
Figure 8.
Anticancer effect of ursolic acid treatment on cofilin-1 protein expression in prostate cancer. Anticancer effect of ursolic acid treatment on cofilin-1 protein expression assessed (A) by western blotting assays and (B) quantification of cofilin-1 protein expression in prostate cancer cells. **P<0.01 compared with 0 µM ursolic acid group.
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