| dc.description.abstract | Prostate cancer (PCa) is the second most commonly diagnosed cancer in men worldwide. Although the growth and metastasis of PCa cells can be regulated by native and synthetic
Danshen compounds (well-known traditional Chinese medicines for treating cardiovascular diseases), the exact mechanisms of their actions are still not clear. Through uses of synthetic Danshen compounds, such as St32c, St32da, and St32db, as well as PCa cell lines, such as LNCaP, DU-145 and PC-3, the present thesis was designed to investigate whether any of them affect the growth of androgen-dependent and androgen-independent PCa cells through modulations of apoptosis and autophagy pathways. In the apoptotic pathway, the three compounds all dose-dependently increased the activity of caspase-9 and caspase-3 in LNCaP, DU-145, and PC-3 cells, as evidenced by increased cleaved forms of caspase-3 and caspase-9 proteins. Interestingly, St32c and St32db generally increased the activity of Bcl-2 in LNCaP
and DU-145, and all three compounds enhanced the cleaved PARP protein levels in LNCaP and DU-145. Treatment of DU-145 cells with a caspase-3 inhibitor (e.g., Z-VAD-FMK) generally antagonized the effect of ST32c, ST32da and ST32db on cell viability. In the autophagy process, St32c tended to increase levels of Beclin-1, Atg5, and Atg7 proteins in all
PCa cell types with dose dependency. Whereas, St32da at 100 μM significantly decreased Atg3 and Atg7 in LNCaP and DU-145 but not PC-3 cells, as well as decreasing Beclin-1 and Atg5
proteins in DU-145 cells. St32db tended to decrease Atg3 and Atg7 proteins in LNCaP, Atg3 protein in DU-145, and Atg3, Atg4B, and Atg7 in PC-3 cells. However, all compounds
increased p62 and pp62 proteins in the three PCa cells and LC3β-II protein in PC-3 cells. In conclusions, the synthetic Danshen compounds vary with chemical structure and the dosage of treatment to inhibit the growth of different types of PCa cells possibly through modulations of varying apoptotic proteins and/or through alterations of particular autophagy protein levels | en_US |