Browse > Article

Effects of Takrisodokyeum Water Extracts on LNCaP Prostate Cancer Cells  

Park, Kwan-Woo (Department of Obstetrics and Gynecology, School of Oriental Medicine, Wonkwnag University)
Kim, Song-Baeg (Department of Obstetrics and Gynecology, School of Oriental Medicine, Wonkwnag University)
Choi, Chang-Min (Department of Obstetrics and Gynecology, School of Oriental Medicine, Wonkwnag University)
Ryu, Do-Gon (Department of Physiology, School of Oriental Medicine, Wonkwnag University)
Kwon, Kang-Beom (Department of Physiology, School of Oriental Medicine, Wonkwnag University)
Publication Information
Journal of Physiology & Pathology in Korean Medicine / v.23, no.5, 2009 , pp. 1154-1160 More about this Journal
Abstract
Androgen receptors (AR) play a crucial role in the development and progression of prostate cancer. Many studies have suggested that prostate cancer cell proliferation is inhibited by AR downregulation, and it has been reported that Takrisodokyeum (TRSDY) induced apoptotic cell death and suppressed tumorigenesis in human leukemia cells. Therefore, this study was conducted to elucidate the mechanism by which TRSDY affects cell growth and AR expression in androgen-dependent prostate cancer cells (LNCaP cells). We investigated the proliferation and apoptosis of LNCaP cells using MTT and DNA fragmentation assays. In addition, we used western blot analysis to assess the effects of TRSDY on the expression of the AR target gene, prostate-specific antigen (PSA). Furthermore, the mechanism of AR downregulation by TRSDY was investigated using EMSA to analyze the binding activity of AR to androgen response elements (ARE). TRSDY significantly suppressed proliferation and induced apoptosis in LNCaP cells. In addition, TRSDY-induced apoptotic cell death was accompanied by activation of caspase-3 and cleavage of its substrate, poly(ADP-ribose) polymerase. TRSDY also inhibited the constitutively expressed- or 5a-dihydrotestosterone (DHT)-induced AR/PSA protein levels. However, these effects were mediated by inhibition of the binding of AR to ARE. TRSDY-mediated AR/PSA downregulation contributes to the inhibition of cell proliferation and the induction of apoptosis in LNCaP human prostate cancer cells. Our findings suggest that TRSDY may be used as a chemopreventive or chemotherapeutic agent for the treatment of prostate cancer.
Keywords
takrisodokyeum; apoptosis; androgen receptor; prostate specific antigen; prostate cancer;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 全國韓醫科大學 肝系內科學敎授. 肝系內科學. 서울, 東洋學硏究院出版部, pp 323-330, 1984
2 Jenster, G. The role of the androgen receptor in the development and progression of prostate cancer. Semin. Oncol. 26(4):407-421, 1999   PUBMED
3 Chen, C.D., Welsbie, D.S., Tran, C., Baek, S.H., Chen, R., Vessella, R., Rosenfeld, M.G., Sawyers, C. L. Molecular determinants of resistance to antiandrogen therapy. Nat. Med. 10(1):33-39, 2004   DOI   ScienceOn
4 Santos, A.F., Huang, H., Tindall, D.J. The androgen receptor: a potential target for therapy of prostate cancer. Steroids 69(2):79-85, 2004   DOI   ScienceOn
5 Pfeifer, B.L., Pirani, J.F., Hamann, S.R., Klippel, K.F. PC-SPES, a dietary supplement for the treatment of hormone-refractory prostate cancer. BJU Int. 85(4):481-485, 2000   DOI   ScienceOn
6 Small, E.J., Frohlich, M.W., Bok, R., Shinohara, K., Grossfeld, G., Rozenblat, Z., Kelly, W.K., Corry, M., Reese, D.M. Prospective trial of the herbal supplement PC-SPES in patients with progressive prostate cancer. J. Clin. Oncol. 18(21):3595-3603, 2000   DOI   ScienceOn
7 Nicholson, D.W., Thornberry, N.A. Caspases: killer proteases. Trends Biochem. Sci. 22(8):299-306, 1997
8 Kanduc, D., Mittelman, A., Serpico, R., Sinigaglia, E.; Sinha, A.A., Natale, C., Santacroce, R., Di Corcia, M.G., Lucchese, A., Dini, L., Pani, P., Santacroce, S., Simone, S., Bucci, R., Farber, E. Cell death: apoptosis versus necrosis (review). Int. J. Oncol. 21(1):165-170, 2002
9 Nakamura, K., Yasunaga, Y., Segawa, T., Ko, D., Moul, J.W., Srivastava, S., Rhim, J.S. Curcumin down-regulates AR gene expression and activation in prostate cancer cell lines. Int. J. Oncol. 21(4):825-830, 2002   PUBMED   ScienceOn
10 Brewster, S.F., Simons, J.W. Gene therapy in urological oncology: principles, strategies and potential. Eur. Urol. 25(3):177-182, 1994   DOI   PUBMED
11 Gittes, R.F. Carcinoma of the prostate. N. Engl. J. Med. 324(4):236-245, 1991   DOI   ScienceOn
12 Taplin, M.E., Bubley, G.J., Shuster, T.D., Frantz, M.E., Spooner, A.E., Ogata, G.K., Keer, H.N, Balk, S.P. Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N. Engl. J. Med. 332(21):1393-1398, 1995   DOI   ScienceOn
13 Fisher, D.E. Pathways of apoptosis and the modulation of cell death in cancer. Hematol. Oncol. Clin. North Am. 15(5):931-956, 2001   DOI
14 김병철, 김진원, 정병주, 우성호, 심효주, 나유진, 김용호, 서호석, 이원희. 복수 동반 간병변 환자의 平胃散 合 胃苓湯加味方 투여 호전 1례. 대한한방내과학회지 27(4):962-968, 2006   과학기술학회마을
15 Hobisch, A., Culig, Z., Radmayr, C., Bartsch, G., Klocker, H., Hittmair, A. Androgen receptor status of lymph node metastases from prostate cancer. Prostate 28(2):129-135, 1996   DOI   ScienceOn
16 Edwards, J., Krishna, N.S., Grigor, K.M., Bartlett, J.M. Androgen receptor gene amplification and protein expression in hormone refractory prostate cancer. Br. J. Cancer. 89(3):552-556, 2003   DOI   ScienceOn
17 Kwon, K.B., Park, B.H., Ryu, D.G. Chemotherapy through mitochondrial apoptosis using nutritional supplements and herbs: a brief overview. J. Bioenerg. Biomembr. 39(1):31-34, 2007   DOI   ScienceOn
18 Huang, W., Shostak, Y., Tarr, P., Sawyers, C., Carey, M. Cooperative assembly of androgen receptor into a nucleoprotein complex that regulates the prostate-specific antigen enhancer. J. Biol. Chem. 274(36):25756-25768, 1999   DOI
19 Hsieh, T.C., Lu, X., Guo, J., Xiong, W., Kunicki, J., Darzynkiewicz, Z., Wu, J.M. Effects of herbal preparation Equiguard on hormone-responsive and hormone-refractory prostate carcinoma cells: mechanistic studies. Int. J. Oncol. 20(4):681-689, 2002   PUBMED   ScienceOn
20 Taplin, M.E., Balk, S.P. Androgen receptor: a key molecule in the progression of prostate cancer to hormone independence. J. Cell. Biochem. 91(3):483-490, 2004   DOI   ScienceOn
21 Yang, Y., Chisholm, G.D., Habib, F.K. The distribution of PSA, cathepsin-D, and pS2 in BPH and cancer of the prostate. Prostate 21(3):201-208, 1992   DOI   ScienceOn
22 Ikezoe, T., Chen, S.S., Yang, Y., Heber, D., Taguchi, H., Koeffler, H.P. PC-SPES: Molecular mechanism to induce apoptosis and down-regulate expression of PSA in LNCaP human prostate cancer cells. Int. J. Oncol. 23(5):1461-1470, 2003   PUBMED   ScienceOn
23 Xing, N., Chen, Y., Mitchell, S., Young, C.Y. Quercetin inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells. Carcinogenesis 22(3):409-414, 2001   DOI   ScienceOn
24 Yang, K.H. Study on Effect of Takrisodokyeum Extract on Antitumoral Activity and Immune Response. The Korean Journal of Oriental Medical Prescription 5: 147-168, 1997   과학기술학회마을   ScienceOn
25 Walsh, P.C. Prospective, multicenter, randomized phase II trial of the herbal supplement, PC-SPES, and diethylstilbestrol in patients with androgen-independent prostate cancer. J. Urol. 173(6):1966-1967, 2005
26 Balk, S.P. Androgen receptor as a target in androgen-independent prostate cancer. Urology 60(3-1):132-138, 138-139, 2002   DOI   PUBMED   ScienceOn
27 Kwon, K.B., Kim, E.K., Shin, B.C., Seo, E.A., Park, J.W., Kim, J.S., Park, B.H., Ryu, D.G. Induction of apoptosis by takrisodokyeum through generation of hydrogen peroxide and activation of caspase-3 in HL-60 cells. Life Sci. 73(15):1895-1906, 2003   DOI   ScienceOn
28 Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65(1-2):55-63, 1983   DOI   ScienceOn
29 Hsieh, T.C., Xiong, W., Traganos, F., Darzynkiewicz, Z., Wu, J.M. Effects of PC-SPES on proliferation and expression of AR/PSA in androgen-responsive LNCaP cells are independent of estradiol. Anticancer Res. 22(4):2051-2060, 2002   PUBMED   ScienceOn
30 Pang, S., Dannull, J., Kaboo, R., Xie, Y., Tso, C.L., Michel, K., deKernion, J.B., Belldegrun, A.S. Identification of a positive regulatory element responsible for tissue-specific expression of prostate-specific antigen. Cancer Res. 57(3):495-499, 1997   PUBMED   ScienceOn
31 Ren, F., Zhang, S., Mitchell, S.H., Butler, R., Young, C.Y. Tea polyphenols down-regulate the expression of the androgen receptor in LNCaP prostate cancer cells. Oncogene, 19(15):1924-1932, 2000   DOI   ScienceOn
32 Mikolajczyk, S.D., Marker, K.M., Millar, L.S., Kumar, A., Saedi, M.S., Payne, J.K., Evans, C.L., Gasior, C.L., Linton, H.J., Carpenter, P., Rittenhouse, H.G. A truncated precursor form of prostate-specific antigen is a more specific serum marker of prostate cancer. Cancer Res. 61(18):6958-6963, 2001   PUBMED   ScienceOn
33 Oh, W.K., Kantoff, P.W., Weinberg, V., Jones, G., Rini, B.I., Derynck, M.K., Bok, R., Smith, M.R., Bubley, G.J., Rosen, R.T., DiPaola, R.S., Small, E.J. Prospective, multicenter, randomized phase II trial of the herbal supplement, PC-SPES, and diethylstilbestrol in patients with androgen-independent prostate cancer. J. Clin. Oncol. 22(18):3705-3712, 2004   DOI   ScienceOn
34 Wang, L.G., Liu, X.M., Kreis, W., Budman, D.R. Down-regulation of prostate-specific antigen expression by finasteride through inhibition of complex formation between androgen receptor and steroid receptor-binditorconsensus in the prom L.r of the PSA gene in LNCaP cells. Cancer Res. 57(4):714-719, 1997   PUBMED   ScienceOn