Journal List > Korean J Urol > v.50(1) > 1005395

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Choi, Min, Oh, Song, and Kang: Effect of Decursin on the Expression of β-Catenin and Matrix Metalloproteinase-7 in Prostate Cancer Cell Lines
Original Article
Korean Journal of Urology

Korean Journal of Urology 2009; 50(1): 81-88.

Published online: 31 January 2009

DOI: https://doi.org/10.4111/kju.2009.50.1.81

Effect of Decursin on the Expression of β-Catenin and Matrix Metalloproteinase-7 in Prostate Cancer Cell Lines

Ik-jun Choi1, Kweonsik Min1, 2, Sangtaek Oh3, Gyu-yong Song4, Dongil Kang1, 2

1Department of Urology, College of Medicine, Inje University, Busan, Korea.

2Paik Institute of Clinical Research, College of Medicine, Inje University, Busan, Korea.

3Pharmaco Genomics Research Center, College of Medicine, Inje University, Busan, Korea.

4College of Pharmacy, Chungnam National University, Daejeon, Korea.

ur0kang@hanmail.net

Received 18 June 2008       Accepted 1 October 2008

Copyright © 2009 The Korean Urological Association

Abstract

Purpose

Alterations in the Wnt/β-catenin pathway are associated with the development and progression of human prostate cancer. Decursin can attenuate the Wnt/β-catenin pathway. We investigated the relationship between the Wnt/β-catenin pathway and decursin in prostate cancer cells.

Materials and Methods

PC-3 and LNCaP cell lines were used. Cell viability was measured with methyl-thiazole tetrazolium bromide (MTT) assays, and cell apoptosis analysis was performed by FACScan. The amount of β-catenin protein after treatment with decursin was measured by Western blot analysis. Expression of MMP-7 mRNA was detected by real-time polymerase chain reaction (RT-PCR).

Results

Death and apoptosis were increased after treatment with decursin 0.5-100 µM in PC-3 and LNCaP cells. This was revealed dose and time-dependent increase of cancer cell death on 24, 48 and 72 hours. FACScan showed an increment of apoptosis on 24, 48 hours. Expression of intracellular β-catenin protein was decreased dose-dependently in both of prostate cancer cell lines. Decursin reduced MMP-7 mRNA expression on 6, 12, 24, 48 hours dose-dependently.

Conclusions

Decursin affects the viability of prostate cancer cells. Increased cancer cell death was associated with increased apoptosis. This study suggests that decursin may play a role in the treatment of prostate cancer.

Keywords: Decursin, Beta-catenin, Matrix metalloproteinase, Prostate

Figures and Tables

Fig. 1
Chemical structure of decursin isolated from the roots of Angelica gigas.
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Fig. 2
The growth rate of prostatic cancer cell lines. (A) LNCaP cell line, (B) PC-3 cell line. *p<0.05 versus control.
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Fig. 3
Effects of decursin-induced apoptosis in prostate cancer cell lines. Cells were incubated for 24 or 48 hours and stained with annexin V and PI. (A) LNCaP cells with 10 µM decursin, (B) LNCaP cells with 50 µM decursin, (C) PC-3 cells with 10 µM decursin, (D) PC-3 cells with 50 µM decursin.
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Fig. 4
Effects of decursin on the expression of β-catenin protein in LNCaP and PC-3 prostatic cancer cells. Total and except membrane β-catenin protein was isolated and Western blot analysis was performed.
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Fig. 5
Effects of decursin on the expression of MMP-7 mRNA in LNCaP and PC-3 prostatic cancer cells. MMP-7 mRNA was isolated and real-time PCR was performed. The bar diagrams (A, B) show expression of MMP-7/GAPDH. *p<0.05, versus untreated control. (C) Comparison of expression of MMP-7 mRNA between LNCaP and PC-3. *p<0.05 (MMP-7: matrix metalloproteinase-7, PCR: polymerase chain reaction, GAPDH: glyceraldehyde-3-phosphate dehydrogenase).
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References

1. Harris KA, Reese DM. Treatment options in hormone-refractory prostate cancer: current and future approaches. Drugs. 2001. 61:2177–2192.
2. Logothetis CJ. Docetaxel in the intergrated management of prostate cancer. Current applications and future promise. Oncology. 2002. 16:6 Suppl 6. 63–72.
3. Han KS, Cho KS, Lee SH, Hong SJ. Estramustine phosphate based chemotherapy for hormone refractory prostate cancer. Korean J Urol. 2007. 48:684–690.
4. Clevers H. Wnt/beta-catenin signaling in development and disease. Cell. 2006. 127:469–480.
5. Umbas R, Schalken JA, Aalders TW, Carter BS, Karthaus HF, Schaafsma HE, et al. Expression of the cellular adhesion molecule E-cadherin is reduced or absent in high-grade prostate cancer. Cancer Res. 1992. 52:5104–5109.
6. Richmond PJ, Karayiannakis AJ, Nagafuchi A, Kaisary AV, Pignatelli M. Aberrant E-cadherin and alpha-catenin expression in prostate cancer: correlation with patient survival. Cancer Res. 1997. 57:3189–3193.
7. Luo J, Lubaroff DM, Hendrix MJ. Suppression of prostate cancer invasive potential and matrix metalloproteinase activity by E-cadherin transfection. Cancer Res. 1999. 59:3552–3556.
8. Nelson WJ, Nusse R. Convergence of Wnt, beta-catenin, and cadherin pathways. Science. 2004. 303:1483–1487.
9. Verras M, Sun Z. Roles and regulation of Wnt signaling and beta-catenin in prostate cancer. Cancer Lett. 2006. 237:22–32.
10. Kim TH, Kim YS, Myoung SC, Lee JH, Won EH. Prostagladin E receptor II and IV increase the expression of martrix metalloproteinase-7 in PC (prostate cancer)-3 cells. Korean J Urol. 2004. 45:478–484.
11. Ahn KS, Sim WS, Kim IH. Decursin: a cytotoxic agent and protein kinase C activator from the root of Angelica gigas. Planta Med. 1996. 62:7–9.
12. Lee S, Lee YS, Jung SH, Shin KH, Kim BK, Kang SS. Anti-tumor activities of decursinol angelate and decursin from Angelica gigas. Arch Pharm Res. 2003. 26:727–730.
13. Yim D, Singh RP, Agarwal C, Lee S, Chi H, Agarwal R. A novel anticancer agent, decursin, induces G1 arrest and apoptosis in human prostate carcinoma cells. Cancer Res. 2005. 65:1035–1044.
14. Song GY, Lee JH, Cho M, Park BS, Kim DE, Oh S. Decursin suppresses human androgen-independent PC3 prostate cancer cell proliferation by promoting the degradation of beta-catenin. Mol Pharmacol. 2007. 72:1599–1606.
15. Jiang C, Lee HJ, Li GX, Guo J, Malewicz B, Zhao Y, et al. Potent antiandrogen and androgen receptor activities of an Angelica gigas-containing herbal formulation: identification of decursin as a novel and active compound with implications for prevention and treatment of prostate cancer. Cancer Res. 2006. 66:453–463.
16. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983. 65:55–63.
17. Dignam JD, Lebovitz RM, Roeder RG. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983. 11:1475–1489.
18. Heinlein CA, Chang C. Androgen receptor in prostate cancer. Endocr Rev. 2004. 25:276–308.
19. Feldman BJ, Feldman D. The development of androgen-independent prostate cancer. Nat Rev Cancer. 2001. 1:34–45.
20. Hyytinen ER, Thalmann GN, Zhau HE, Karhu R, Kallioniemi OP, Chung LW, et al. Genetic changes associated with the acquisition of androgen-independent growth, tumorigenicity and metastatic potential in a prostate cancer model. Br J Cancer. 1997. 75:190–195.
21. Chen G, Shukeir N, Potti A, Sircar K, Aprikian A, Goltzman D, et al. Up-regulation of Wnt-1 and beta-catenin production in patients with advanced metastatic prostate carcinoma: potential pathogenetic and prognostic implications. Cancer. 2004. 101:1345–1356.
22. Saha B, Arase A, Imam SS, Tsao-Wei D, Naritoku WY, Groshen S, et al. Overexpression of E-cadherin and beta-catenin proteins in metastatic prostate cancer cells in bone. Prostate. 2008. 68:78–84.
23. Whitaker HC, Girling J, Warren AY, Leung H, Mills IG, Neal DE. Alterations in beta-catenin expression and localization in prostate cancer. Prostate. 2008. 68:1196–1205.
24. Bismar TA, Humphrey PA, Grignon DJ, Wang HL. Expression of beta-catenin in prostatic adenocarcinomas: a comparison with colorectal adenocarcinomas. Am J Clin Pathol. 2004. 121:557–563.
25. Jaggi M, Johansson SL, Baker JJ, Smith LM, Galich A, Balaji KC. Aberrant expression of E-cadherin and beta-catenin in human prostate cancer. Urol Oncol. 2005. 23:402–406.
26. Van Veldhuizen PJ, Ray G, Banerjee S, Dhar G, Kambhampati S, Dhar A, et al. 2-methoxyestradiol modulates beta-catenin in prostate cancer cells: a possible mediator of 2-methoxyestradiol-induced inhibition of cell growth. Int J Cancer. 2008. 122:567–571.
27. Kader AK, Liu J, Shao L, Dinney CP, Lin J, Wang Y, et al. Matrix metalloproteinase polymorphisms are associated with bladder cancer invasiveness. Clin Cancer Res. 2007. 13:2614–2620.
28. Leeman MF, Curran S, Murray GI. New insights into the roles of matrix metalloproteinases in colorectal cancer development and progression. J Pathol. 2003. 201:528–534.
29. Brabletz T, Jung A, Dag S, Hlubek F, Kirchner T. Beta-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer. Am J Pathol. 1999. 155:1033–1038.
30. Zeng ZS, Shu WP, Cohen AM, Guillem JG. Matrix metalloproteinase-7 expression in colorectal cancer liver metastases: evidence for involvement of MMP-7 activation in human cancer metastases. Clin Cancer Res. 2002. 8:144–148.
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