Inhibitory Effects of a Black Cohosh (Cimicifuga racemosa) Extract on Prostate Cancer

Abstract

The Cimicifuga racemosa extract BNO 1055 (CR) inhibits proliferation of human prostate cancer-derived LNCaP cells. Therefore, we tested the capability of this extract to inhibit formation and/or proliferation of tumors induced by subcutaneous (s. c.) inoculation of LNCaP cells in immunodeficient nu/nu mice. After inoculation of 1 million cells, 12 of 18 animals developed solid tumors while tumor development was seen in only 5 of 18 CR-treated animals and the size of the latter at termination of the experiments 10 weeks after inoculation was significantly smaller than in the control animals. Upon histological inspection, the amount of tumor tissue in the control animals was significantly larger than in the CR-treated animals while in the latter connective tissue was predominant. The CR treatment did not affect serum testosterone levels significantly regardless of whether the animals developed tumors or not. It is concluded that compounds in CR inhibit tumor development, proliferation and dignity of the tumors following s. c. inoculation of LNCaP cells. Hence, the CR extract may prove to be efficient in preventing and treatment of prostate cancer.

Key words

Black cohosh - prostate cancer - LNCaP cells - nu/nu mice

References

• 1 Ryan C J, Small E J. Progress in detection and treatment of prostate cancer.  Curr Opin Oncol. 2005;  17 257-60
• 2 Denis L J, Griffiths K. Endocrine treatment in prostate cancer.  Semin Surg Oncol. 2000;  18 52-74
• 3 Heinlein C A, Chang C. Androgen receptor in prostate cancer.  Endocr Rev. 2004;  25 276-308
• 4 Hsing A W, Reichardt J K, Stanczyk F Z. Hormones and prostate cancer: current perspectives and future directions.  Prostate. 2002;  52 213-35
• 5 Borst S E, Lee J H, Conover C F. Inhibition of 5{alpha}-reductase blocks prostate effects of testosterone without blocking anabolic effects.  Am J Physiol Endocrinol Metab. 2005;  288 E222-7
• 6 Chen W, Zouboulis C C, Orfanos C E. The 5 alpha-reductase system and its inhibitors. Recent development and its perspective in treating androgen-dependent skin disorders.  Dermatology. 1996;  193 177-84
• 7 Smith C M, Ballard S A, Worman N, Buettner R, Masters J R. 5 alpha-reductase expression by prostate cancer cell lines and benign prostatic hyperplasia in vitro .  J Clin Endocrinol Metab. 1996;  81 1361-6
• 8 Negri-Cesi P, Poletti A, Colciago A, Magni P, Martini P, Motta M. Presence of 5alpha-reductase isozymes and aromatase in human prostate cancer cells and in benign prostate hyperplastic tissue.  Prostate. 1998;  34 283-91
• 9 Jarry H, Thelen P, Christoffel V, Spengler B, Wuttke W. Cimicifuga racemosa extract BNO 1055 inhibits proliferation of the human prostate cancer cell line LNCaP.  Phytomedicine. 2005;  12 178-82
• 10 Rajah R, Katz L, Nunn S, Solberg P, Beers T, Cohen P. Insulin-like growth factor binding protein (IGFBP) proteases: functional regulators of cell growth.  Prog Growth Factor Res. 1995;  6 273-84
• 11 Zhau H E, Li C L, Chung L W. Establishment of human prostate carcinoma skeletal metastasis models.  Cancer. 2000;  88 2995-3001
• 12 Peehl D M, Cohen P, Rosenfeld R G. The insulin-like growth factor system in the prostate.  World J Urol. 1995;  13 306-11
• 13 Culig Z, Hobisch A, Cronauer M V, Hittmair A, Radmayr C, Bartsch G. et al . Activation of the androgen receptor by polypeptide growth factors and cellular regulators.  World J Urol. 1995;  13 285-9
• 14 Lazier C B, Thomas L N, Douglas R C, Vessey J P, Rittmaster R S. Dutasteride, the dual 5alpha-reductase inhibitor, inhibits androgen action and promotes cell death in the LNCaP prostate cancer cell line.  Prostate. 2004;  58 130-44
• 15 Thompson I M, Goodman P J, Tangen C M, Lucia M S, Miller G J, Ford L G. et al . The influence of finasteride on the development of prostate cancer.  N Engl J Med. 2003;  349 215-24
• 16 Thompson I M, Klein E A, Lippman S M, Coltman C A, Djavan B. Prevention of prostate cancer with finasteride: US/European perspective.  Eur Urol. 2003;  44 650-5
• 17 van Weerden W M, Romijn J C. Use of nude mouse xenograft models in prostate cancer research.  Prostate. 2000;  43 263-71
• 18 Yin J J, Pollock C B, Kelly K. Mechanisms of cancer metastasis to the bone.  Cell Res. 2005;  15 57-62
• 19 Logothetis C J, Lin S H. Osteoblasts in prostate cancer metastasis to bone.  Nat Rev Cancer. 2005;  5 21-8
• 20 Helterbrand J D, Higgs RE J r, Iversen P W, Tysarczyk-Niemeyer G, Sato M. Application of automatic image segmentation to tibiae and vertebrae from ovariectomized rats.  Bone. 1997;  21 401-9
• 21 Seidlova-Wuttke D, Hesse O, Jarry H, Christoffel V, Spengler B, Becker T. et al . Evidence for selective estrogen receptor modulator activity in a black cohosh (Cimicifuga racemosa) extract: comparison with estradiol-17beta.  Eur J Endocrinol. 2003;  149 351-62
• 22 Hostanska K, Nisslein T, Freudenstein J, Reichling J, Saller R. Cimicifuga racemosa extract inhibits proliferation of estrogen receptor-positive and negative human breast carcinoma cell lines by induction of apoptosis.  Breast Cancer Res Treat. 2004;  84 151-60
• 23 Hostanska K, Nisslein T, Freudenstein J, Reichling J, Saller R. Evaluation of cell death caused by triterpene glycosides and phenolic substances from Cimicifuga racemosa extract in human MCF-7 breast cancer cells.  Biol Pharm Bull. 2004;  27 1970-5
• 24 Chen Y, Yu D C, Charlton D, Henderson D R. Pre-existent adenovirus antibody inhibits systemic toxicity and antitumor activity of CN706 in the nude mouse LNCaP xenograft model: implications and proposals for human therapy.  Hum Gene Ther. 2000;  11 1553-67
• 25 Rosen C J. Insulin-like growth factor I and bone mineral density: experience from animal models and human observational studies.  Best Pract Res Clin Endocrinol Metab. 2004;  18 423-35
• 26 Spelsberg T C, Subramaniam M, Riggs B L, Khosla S. The actions and interactions of sex steroids and growth factors/cytokines on the skeleton.  Mol Endocrinol. 1999;  13 819-28