Decursin Inhibits Human Androgen-Independent PC3 Prostate Cancer Cell Spread by Accelerateing the Degradation of Catenin
Changes to the list / catenin Wnt signaling have been sick with the growth and development of 3 prostate cancer in humans. Decursin pyranocoumarin from Korea gigas Angelica root isolation inhibits the growth of androgen-independent cells in prostate cancer, but little is known about how their actions. With a couple of function screen, we found that Decursin decreases the Wnt /-catenin signaling. Decursin antagonizes catenin transcription reaction (CRT), which is induced by Wnt 3 prostate cancer a conditioned medium and LiCl, by promoting the degradation of-catenin. Furthermore, the expression of cyclin D1 Decursin removed and c-myc, the target genes downstream of-catenin and thus prevents cell growth of prostate cancer PC3. WithCOH Decursinol But when the CH3 () = 2CC take CHCCOOCside Decursin chain had no effect on CRT, the level of intracellular catenin, or PC3 cell proliferation. Our results show that Decursin has anti-cancer cells in prostate cancer by inhibiting the Wnt /-catenin signaling pathway.
Wnts, cysteine-rich secreted glycoproteins that play an important role in cell proliferation, fate determination and movement during development (Wodarz and Nusse, 1998? Polacks, 2000). Depending on the type of Wnt and frizzled (Fz) receptor induced to activate one of three intracellular signaling pathways: in / Wnt catenin signaling, the path of planar cell polarity and Wnt/Ca2 path + (KHL, et al. 2000 ? Winklbauer et al., 2001, Giles et al., 2003). Among them is to understand better / Wnt catenin signaling is activated by the combination of Wnt1, Wnt3a and Wnt8 with Fz receptors and low density lipoprotein receptor-related protein 5 / 6 coreceptors (Giles and al., 2003). The road is primarily the level of cytosolic-catenin, which activates several genes regulated. In the absence of a signal Wnt, casein kinase 1 and glycogen synthase kinase-3 (GSK-3), which in turn phosphorylates a complex with adenomatous polyposis coli (APC) / Axin,-catenin at Ser33, Ser37, Thr41 and form Ser45 ( Liu et al., 2002). Catenin phosphorylation subsequently recognized by F-box-transducin repeat containing protein (-TRCP), a component of the ubiquitin ligase complex, which the degradation of-catenin (Latre et al., 1999). Activation of receptor by the ligand Wnt negatively regulates GSK-3, leading to accumulation of cytoplasmic-catenin (Lee et al., 2003a).
Prostate cancer is one of the most common cancers diagnosed and the second leading cause of cancer death in men (Jemal et al., 2005). Malfunction in the list / catenin Wnt signaling is a common event during tumorigenesis of prostatic hyperplasia (Barker and Clevers, 2000). For example, changes in the gene APC, including somatic mutations, promoter hypermethylation, often observed in prostate cancer, since mutations in the gene encoding-catenin (Cheshire et al. 2000? Gerstein et al. 2002). In fact, the level of intracellular-catenin is significantly elevated in more than 20% of prostate tumors progress, 77% of node metastatic prostate cancer lymph nodes, and 85% of bone metastases of prostate cancer (Chesire and Isaac, 2002). -Catenin in the nucleus, where it complexes with T-cell factor (TCF) / lymphocyte enhancer factor transcription factors family activate the expression of Wnt /-catenin responding genes such as c-myc, cyclin D1, and metalloproteinase shift -7, which play important role in tumor formation and metastasis (He et al., 1998, Tetsu and McCormick, 1999, Takahashi et al., 2002). Thus, the reduction is abnormally regulated by intracellular-catenin, a potential therapeutic strategy for chemoprevention and treatment of prostate cancer.
Decursin a pyranocoumarin found in the roots of Angelica gigas Nakai, which has been used traditionally to treat anemia and other diseases (Chi and Kim, 1970). Decursin is cytotoxic to leukemia cells by a mechanism of protein kinase C and reactive oxygen species, and has an anti-tumor activity in mice inoculated with sarcoma cells (Lee et al. 2003b Kim et al., 2005).
It was reported that Decursin suppresses growth and promotes apoptosis in cells of human prostate carcinoma (Yim et al., 2005, Jiang et al., 2006). Furthermore, the CH3 () 2CC = CHCCOOCside seems Decursin chain, replaced by a group OH Decursinol compared to the fight against cancer activity is required (Yim et al., 2005, Guo et al. 2007). In this study, we found Decursin as an inhibitor of Wnt /-catenin signaling pathway cell-based survey of small molecules. Decursin can inhibit cell growth of prostate cancer by promoting degradation of intracellular catenin.
Preparation and Decursin Decursinol. (+)-Decursinol prepared from the roots of A. gigas, as previously described (Lee et al., 2006). It is the composition of the solution Decursinol Decursin 3,3 dimethylacrylic additional dicyclohexylcarbodiimide and 4-dimethylaminopyridine in 350 ml dry methylene chloride. The reaction mixture was stirred at room temperature for 24 hours and filtered. The filtrate was evaporated under reduced pressure and purified by flash chromatography (yield n-hexane/ethyl acetate = 10:1 1:1) (+)-form Decursin a white powder. Decursin structures of (+)-Decursinol and (+)-determined by comparing the mass spectrometry and NMR spectra confirmed, as previously (Lim et al., 2001).
Cell culture, transfection and assay luciferase. HEK293, PC-3, and Wnt3a-producing L cells were obtained from the American Type Culture Collection (Manassas, VA) and the Dulbecco modified Eagle’s medium supplemented with 10% managed fetal calf serum, 120 g / ml penicillin, and 200 g / ml streptomycin. Wnt3a conditioned (using Wnt3a CM) was prepared as described previously (Gwak et al., 2006). Briefly, Wnt3a-producing L cells grown in the Dulbecco modified Eagle’s medium containing 10% fetal calf serum for 4 days. The medium was collected and sterilized with a filter of 0.22-m. Fresh medium was added, cells cultured for 3 days and medium was collected and combined with the previous environment. Transfection was with lipofectamine 2000 (Invitrogen, Carlsbad, CA) according to manufacturer’s instructions. The luciferase assay was performed using a double test luciferase kit (Promega, Madison, WI).
Plasmid construction. Human Frizzled-1 cDNA was cloned as described previously (Cho et al., 2005). Reporter plasmids containing the promoter of cyclin D1 were introduced to strengthen the areas of implementation, the TCF-4 response elements housed prepared by polymerase chain reaction and incorporated into PRL-null vector, obtaining pCyclinD1-RL. The pFOPFlash pTOPFlash reporter and plasmids were obtained from Upstate Biotechnology (Lake Placid, NY). The dominant negative-TRCP (-TRCP) expression plasmid was a gift from Mr.
Davis (Hadassah-Hebrew University Medical School, Jerusalem, Israel). pCMV-RL and PSV-FL plasmids were purchased from Promega.
Screening for small molecule inhibitors of Wnt /-catenin signaling. The journalist and control HEK293 cell line was created as described previously (Park et al., 2006). The cells were grown in 96-well plates inoculated at 15,000 cells / well in duplicate, and for 24 adults Wnt3a CM was added, followed by chemicals, including coumarins, flavonoids, terpenes and naphthoquinones have introduced the wells at a final concentration of 30 g / ml was added. After 15 hours, the test plates for Firefly luciferase activity and cell viability.
Western blot. The cytosolic fraction was prepared as described previously (Dignam et al., 1983). Proteins were transferred from gel electrophoresis SDS-polyacrylamide gradient gel 4 to 12% (Invitrogen) and nitrocellulose membranes (Bio-Rad Laboratories, Hercules, CA). The membranes were blocked with 5% fat-free milk and probed with anti – catenin (BD Transduction Laboratories, Lexington, KY), anti-cyclin D1 (Santa Cruz Biotechnology, Santa Cruz, CA), anti-myc (Santa Cruz Biotechnology) and anti-actin (Cell Signaling Technology, Danvers, MA). The membranes were then in horseradish peroxidase-conjugated anti-mouse-IgG or anti-rabbit IgG (Santa Cruz Biotechnology) and incubated visualized using enhanced chemiluminescence system (Santa Cruz Biotechnology).
RNA extraction and RT-PCR semi-quantitative. Total RNA was isolated with reagent TRIZOL (Invitrogen) according to manufacturer’s instructions. cDNA synthesis, reverse transcription reaction and polymerase chain reaction were as above (outlined Park et al., 2006). The amplified DNA was separated by 2% agarose gels and stained with ethidium bromide.
Cell Viability Assay. The cells incubated in 96-well plates and treated for 48 hours Decursin discussed the viability of cells from each sample was measured in triplicate with CellTiter-Glo kit assay (Promega), according to the manufacturer’s instructions.
Locating Decursin as an inhibitor of Wnt /-catenin pathway. To identify cell-permeable small molecules capable of using the inhibition of Wnt /-catenin signaling pathway, we have a cell-based control system. Cells HEK293 Reporter transfected stable reporter topflash luciferase -catenin/Tcf-dependent synthetic and human Frizzled-1 expression plasmids were omitted in 96-well plate. After the addition of Wnt3a CM and each connection will be monitored topflash reporter microplate reader (Figure 1A). These compounds identified by the image Decursin (Figure 1B). As in Fig. 1C, Decursin caused dose-dependent reduction of Wnt3a CM-induced catenin transcription reaction (CRT), approximately 80% of Decursin CRT was blocked in a concentration of 200 M. In contrast, the activity has a negative-catenin / TCF reporter FOPFlash control with mutated binding elements not of incubation with Decursin and Wnt3a CM (Fig. 1C) changed. Under these conditions, no cytotoxic effect was observed by Decursin (data not shown). These results indicate that Decursin specifically inhibits Wnt /-catenin signaling.
Fig. 1. Locating Decursin as a small molecule inhibitor of Wnt /-catenin signaling. A test for substances that inhibit the Wnt /-catenin signaling. Topflash compounds modulating the activity of reporter examined using the HEK293 reporter cells. The controls were tested in the presence or absence of Wnt3a CM. B, the chemical structure of Decursin. C, a dose-dependent inhibition of CRT. HEK293 reporter and control cells were incubated with the indicated concentrations Decursin presence of Wnt3a CM. After 15 hours luciferase activity was determined. Topflash activity relative light unit (RLU) normalized to CellTiter-Glo (Promega) activity was reported. The results are the average of three tests and bars indicate the standard deviation. * P 0,05, ** P 0,01, compared with controls of the vehicle.
Promoted Decursin proteasome-mediated degradation of-catenin. The list / CRT Wnt-catenin signaling pathway is largely determined by the level of intracellular catenin, which regulates the expression of many target genes tested. To determine whether Decursin affect the level of intracellular-catenin, we analyzed by Western blot with anti – catenin antibodies for the amount of cytosolic catenin setting Decursin HEK293 cells were reported. As in Fig. 2A, incubation with Decursin resulted in down-regulation of-catenin that had accumulated in the presence of Wnt3a. The next step was to examine whether the expression of mRNA Decursin-catenin in HEK293 cells using reporter RT-PCR semi-quantitative reduction. Unlike the protein-catenin, expression of mRNA-catenin are all concentrations used Decursin unchanged, suggesting that Decursin Wnt /-catenin signaling by reducing the protein-catenin, not the expression 芦-catenin mRNA (Figure 2B inhibitor). It has been shown previously that the level of intracellular catenin is regulated by ubiquitin-dependent proteolysis (Aberle et al., 1997). To determine whether Decursin induced down-regulation of-catenin by the proteasome is to be MG-132 proteasome-mediated degradation of proteins that inhibit taught. Decursin caused significant reductions in the level of-catenin in HEK293 reporter cells (Fig. 2C), but the result was Decursin by the addition of MG-132 (Fig. 2C) did not materialize. Taken together, these results suggest that Decursin Wnt /-catenin signaling pathway inhibition on the degradation of proteasome-mediated-catenin.
Fig. 2. Decursin promotes-catenin degradation via proteasome. One was cytosolic proteins from HEK293 cells with the reporter or vehicle (DMSO) or indicated concentrations of Decursin presence of Wnt3a CM for the preparation of treatment at 15 hours and then subjected to Western blot antibodies catenin. B, RT-PCR semi-quantitative-catenin and glyceraldehyde-3-phosphate dehydrogenase was with total RNA from HEK293 reporter cells or vehicle (DMSO) or indicated concentrations of Decursin presence of Wnt3a CM prepared 15 hours C, cytosolic proteins from HEK293 reporter cells were incubated with vehicle (DMSO) or Decursin (100 million) in the presence or absence of Wnt3a CM, prepared suspension H-132 mg (20 M), for 8 people, have been to Western blot with anti – antibody catenin. In A and C, to confirm equal loading, the spot with anti-actin reprobed.
-TRCP but not GSK-3 is necessary for Decursin was mediated degradation of-catenin. Since the phosphorylation of-catenin by GSK-3 and then with-TRCP leads to degradation of catenin (Winston et al., 1999), will determine whether suspension-Decursin of Wnt /-catenin signaling pathway requires GSK – 3 activity. To this end, HEK293 reporter cells with LiCl, an inhibitor of GSK-3 (Klein and Melton, 1996), were incubated in 3A increased CRT (Fig.). Interestingly, LiCl caused CRT Decursin deleted (Fig. 3A). Furthermore, Western blot analysis shows that the amount of Decursin-catenin induced by LiCl (Figure 3B) that the suspension of Decursin Wnt /-catenin signaling pathway is reduced regardless of GSK-3. It also examined whether the TRCP is required for Decursin caused the degradation of-catenin. As in Fig. 3C, ectopic expression of dominant negative form of-TRCP (TRCP), which interacts with catenin phosphorylated but is unable to form SCF-TRCP-ubiquitin ligase complex (Hart et al., 1999), abolished the Decursin – with mediated degradation of-catenin. These results indicate that promotes degradation of-a-catenin Decursin TRCP dependent mechanism.
Fig. 3. Decursin catenin degradation caused by a mechanism independent of GSK-3 dependent and TRCP. A journalist from HEK293 cells incubated with Decursin presence of 20 mM LiCl. After 15 hours luciferase activity was determined. Topflash activity relative light unit (RLU) normalized to CellTiter-Glo (Promega) activity was reported. The results are the average of three tests and bars indicate the standard deviation. * P 0,05, ** P 0,01, compared with controls of the vehicle. B, cytosolic proteins were prepared from HEK293 reporter cells with either vehicle (DMSO) or increasing amounts Decursin presence of 20 mM LiCl for 15 hours and then treated catenin antibody Western blot. C, HEK293 cells with a plasmid expressing-TRCP then transfected with either vehicle (DMSO) or incubated Decursin (100 million) in the presence of Wnt3a CM for 15 h. cytosolic proteins were subjected to Western blot with anti-catenin. In B and C, staining with anti-actin was reprobed as loading control.
Attenuated Decursin the Wnt /-catenin pathway in cells of prostate cancer. As pastor of chemoprevention as recently Decursin for prostate cancer identified cells (Yim et al., 2005, Jiang et al., 2006), we examined whether Decursin also eliminates the Wnt /-catenin signaling pathway in prostate cancer cells The often show abnormally high intracellular-catenin (Barker and Clevers, 2000). Androgen-independent PC-3 prostate cancer cells were transiently transfected with topflash followed by incubation with increasing amounts Decursin. As a reporter in HEK293 cells Decursin deleted CRT in PC3 cells (Fig. 4A). Evaluated in conjunction with this experience, we, the level of cytosolic-catenin in PC3 cells treated Decursin. According to our findings in HEK293 cells by Western blot analysis showed that-catenin is down regulated in a concentration-dependent manner (Fig.
4B). In addition, MG-132 abolished Decursin induced down-regulation of-catenin in PC3 cells (Fig. 4C). These results indicate that promotes Decursin catenin degradation in prostate cancer cells.
Fig. 4. Decursin promotes degradation of-catenin in PC-3 prostate cancer cells. One was topflash and PC3 cells with pCMV-RL plasmids and incubated with cotransfection Decursin for 15 h. Luciferase activities were measured 39 hours after transfection. Topflash activity is reported relative light unit (RLU), normalized to Renilla luciferase reniformis. The results are the average of three tests and bars indicate the standard deviation. ** P 0,01, compared with controls of the vehicle. B. protein from the cytosol of PC3 cells with vehicle (DMSO) or Decursin treated for 15 hours to prepare and then subjected to Western blot antibodies catenin. C, cytosolic proteins from PC3 cells were prepared with the vehicle (DMSO) or Decursin (100 M) incubated and exposed to subject MG-132 (20 million) for 8 hours, then Western blot anti – antibody catenin. In B and C, to confirm equal loading, the spot with anti-actin reprobed.
Decursin suppress gene expression catenin-dependent and inhibited cell proliferation of prostate cancer. Then consider if Decursin catenin-dependent gene expression affected. For this purpose, PC 3 prostate cancer cells transfected with a reporter containing the construction of the promoter of cyclin D1, which contains a region -catenin/TCF-4-responsive then incubated with various concentrations of Decursin. As in Fig. 5A, an active supporter of cyclin D1 repressed by Decursin. Also measured the mRNA and protein expression of cyclin D1 in PC3 cells treated Decursin. According to our results for the promoter of cyclin D1, a dose-dependent decrease in cyclin D1 mRNA and protein expression was observed in response) Decursin (Fig. 5, B and C. Furthermore, the expression of c-myc, a target set under-catenin (He et al are., 1998) were also significantly reduced in PC 3 prostate cancercells after incubation with Decursin (Fig. 5D). Recently, inhibition of Wnt /-catenin signaling by expression of Frzb / Frizzled-related protein that is secreted antagonist Wnt, suppresses the proliferation of androgen-dependent and independent cell cancer of the prostate (Zi et al excreted., 2005 , Horvath et al., 2007). Moreover, cyclin D1 mediate a complex with cyclin-dependent kinase 4 / 6 shapes, growth factor-dependent G1-phase progression (Sherr, 1996). As Decursin inhibits Wnt /-catenin signaling and the expression of cyclin D1, we examined whether Decursin reduced growth of cells PC3. PC3 cells incubated with different concentrations Decursin and cell growth was monitored. As in Fig. 5E, Decursin effectively PC3 cell growth in a concentration-dependent deleted.
Fig. 5. Decursin inhibit gene expression-catenin-dependent. One was co-transfected PC3 cells with cyclin D1-RL and pSV40-FL, and then the amount shown Decursin incubated for 15 hours luciferase activity measured 39 hours after transfection. Cyclin D1 promoter activity is reported as relative light unit (AVC), normalized to the activity of Firefly luciferase. The results are the average of three tests and bars indicate the standard deviation. * P 0,05, compared with controls of the vehicle. B, semiquantitative RT-PCR for cyclin D1 and glyceraldehyde-3-phosphate dehydrogenase was prepared with total RNA from PC3 cells with vehicle (DMSO) or 15 hours treated Decursin C and D were PC3 cells with vehicle (DMSO) or Decursin for 15 hours, then export the cells were incubated for Western blot anti-cyclin D1 (C) and anti-myc (D) antibodies prepared. To confirm equal loading, the spots were reprobed anti-actin. E PC3 cells were incubated with increasing amounts Decursin and cell viability was determined by assay CellTiter Glo (Promega). The results show the average of three experiments and bars indicate the standard deviation. * P 0,05, ** P 0,01, compared with controls of the vehicle.
If Decursinol / catenin Wnt. Decursinol are similar to Decursin missing CH3 () 2CC = CHCCOOCside chain (Figure 6a). A recent study showed that low Decursinol fight cancer compared with Decursin, suggesting that lack the chain of reactions may be responsible for Decursin mediated inhibition of cell growth of prostate cancer (Yim et al., 2005). To better analyze the relationship between structure and function of these compounds, we Decursinol result in Wnt /-catenin signaling. As a journalist, HEK293 cells were incubated with no significant Decursinol Wnt3a-induced CRT was observed, in contrast to our results with Decursin (Fig. 6B). Do not fall under this Decursinol not follow) the level of cytosolic-catenin in HEK293 reporter cells or PC3 cells in each of the concentrations tested (Fig. 6, C and D, suggesting that it could cause deterioration The Decursinol – catenin. As expected, Decursinol not repress the expression of cyclin D1 in PC3 cells (6th), and had no effect on growth at concentrations of 50 to 100 meters, but increased by about 20% concentration 200 m (Fig. 6E). Taken together, these results indicate that CH3 () = 2CC series CHCCOOCside Decursin is to inhibit the Wnt pathway critical /-catenin signaling and anti-cancer compound in PC3 cells.
Fig. 6. Decursinol not inhibit the Wnt /-catenin signaling. A structure, Decursinol chemistry. B, HEK293 reporter cells were incubated with the indicated concentrations Decursinol presence of Wnt3a CM. After 15 hours luciferase activity was determined.
Topflash activity relative light unit (RLU) normalized to CellTiter-Glo (Promega) activity was reported. The results are the average of three tests and bars indicate the standard deviation. * P 0,05, compared with controls of the vehicle. C and D, cytosolic proteins that journalists from the cells HEK293 (C) or treatment of PC3 cells (D) or vehicle (DMSO) or indicated concentrations of Decursinol cm presence Wnt3a (C) for 15 hours and then prepared for Western subjected to blot with antibodies to-catenin. C, cell extracts prepared from PC3 cells with either vehicle (DMSO) or indicated concentrations of Decursinol Western blot for anti-cyclin D1 antibody therapy. F Decursinol PC3 cells were incubated with increasing amounts and cell viability was determined by assay CellTiter Glo (Promega). The results show the average of three experiments and bars indicate the standard deviation. * P 0,05, compared with controls of the vehicle. In C, D and E stains with anti-actin reprobed to confirm equal loading.
Involving abnormal accumulation of intracellular catenin in the development of prostate cancer at an early stage of formation of primary damage, and an advanced, hormone-refractory stage (Barker and Clevers, 2000). With a couple of function screen, we showed that Decursin suppresses Wnt /-catenin signaling pathway by promoting degradation of-catenin. The level of intracellular catenin is mainly in two ways, a GSK3-dependent pathway regulated and Siah-dependent pathway. GSK3-dependent pathway, the residue N-terminal-catenin is a multiprotein complex of APC, Axin and GSK-3 phosphorylation (Hart et al., 1998), leading to deterioration of-catenin by a mechanism dependent ubiquitin (Aberle et al., 1997). The Siah-dependent way, Siah-1 interacts with the C-terminus of APC, which recruits the complex of ubiquitin and promotes degradation of-catenin by GSK-3-and-TRCP-independent (Liu et al. 2001 ). In this study Decursin capable of intracellular degradation of-catenin presence of Wnt3a and LiCl, which is known to inhibit the GSK-3, suggesting that GSK3 is not required Decursin-catenin degradation of mediation. Furthermore, overexpression of-TRCP-removed from Decursin catenin degradation suggests that TRCP is required for the degradation of-catenin Decursin mediation. These data show that promotes the degradation Decursin-catenin by a mechanism other than those described above. We intend to investigate the mechanism Decursin-catenin caused by the deterioration of the future.
Intracellular-catenin promotes the development of prostate cancer and in-depth -catenin/TCF -catenin/androgen-Rezeptor (AR) pathways (Chesire and Isaac, 2002). -catenin/TCF Mode activation promotes proliferation and inhibits apoptosis of prostate cancer cells (the size et al., 2003). -catenin/AR Way,-catenin interacts with AR, which is upregulated in the activity of AR in a ligand-dependent manner, which supports the development of prostate cancer cells (Mulholland et al., 2003). Recently been shown to inhibit Decursin growth and cell death in both androgen-dependent and independent cell cancer of the prostate (Yim et al., 2005). Jiang et al. Proposed (2006), that cell proliferation Decursin androgen-dependent LNCaP inhibit the inactivation of RA, including inhibition of androgen-stimulated AR nuclear translocation and down-regulate the expression of protein AR. Here, we note that Decursin CRT suppressed, and promoted the degradation of intracellular catenin in androgen-independent PC3 cells. The expression of different target-catenin, cyclin D1, including c-myc, which played an important role in tumor growth and cell cycle progression (Utsunomiya et al., 2001), by Decursin deleted in PC3 cells. This result shows that Decursin inhibits cell proliferation by impressive -catenin/TCF of androgen-independent cells, not by the inactivation of how -catenin/AR. Consistent with this idea, recent studies have shown that inhibition of Wnt /-catenin signaling by expression of a competitor Wnt, as Frzb / secreted Frizzled-related protein-3 prostate cancer and suppresses the dominant negative version LRP5 cell growth PC3 (ZI et al., 2005, Horvath et al., 2007).
Decursinol pyranocoumarin a kernel CH3 () contains 2CC = string CHCCOOCside Decursin (Fig. 6a), is one of the most common compounds in the roots of A. gigas Korean (Yim et al., 2005). It has been suggested previously that the side chain Decursin fight cancer hormone-resistant DU145 cells in prostate cancer (Yim et al., 2005), and the side chain of Decursin demonstrated to provide an anti – PA in cells prostate cancer LNCaP (Guo et al., 2007). Loss of this study, the properties of Decursinol Decursin had no effect on Wnt3aCM caused CRT, the intracellular-catenin or the expression of genes catenin-dependent reporter in HEK293 cells and PC3. Interestingly Decursin had a strong anti-proliferative for PC3 cells, not in the preamble, not Decursinol (Fig. 5E and 6E). The different effects of these substances on cell proliferation PC-3 prostate cancer, according to the opposite effects on Wnt /-catenin signaling pathway, suggesting that inhibition of Wnt /-catenin signaling pathway is a mechanism regulating the central Decursin inhibiting the proliferation cells of PC-3 prostate cancer.
In conclusion, we have to fight 3 prostate cancer Decursin androgen-independent cancer cells by cells of the 3 prostate cancer display. Decursin inhibited the Wnt /-catenin signaling by promoting degradation of-catenin. Also found that CH3 () 2CC = string CHCCOOCside Decursin function, such that inhibition of Wnt signaling is essential /-catenin signaling pathway and cell proliferation.
Taken together, our results facilitate the development of novel cancer therapies in 3 prostate cancer.
