Introduction to Porstate Cancer and Its Treatment

Prostate cancer is the second most common cancer in men after lung cancer. It occurs when a malignant tumor forms in the tissue of the prostate, a gland in the male reproductive system. It mainly affects older men; data indicates that more than 70 percent of men diagnosed with prostate cancer each year are over 65. Figures from the United States National Cancer Institute showed that there were over 230,000 new cases of prostate cancer in the U.S. in 2005 and more than 30,000 people died of the disease.1 Prostate cancer cells require the hormone testosterone to support their growth; hence it is a common target for therapeutic intervention in patients with prostate cancer. Hormonal therapy (anti-androgen therapy) is designed to prevent testosterone from being released or to stop it acting on the prostate cancer cells. Virtually all prostate cancers initially respond to treatment with anti-androgens. However, tumors may become resistant to hormonal therapy because some prostate cancer cells can grow in the absence of testosterone, and hence hormonal therapy gradually has less effect in controlling tumor growth. 2 Therefore, this is not a perfect strategy in the treatment of prostate cancers, and it does not cure the disease. Because of a relative lack of cancer-specific and clinical symptoms, prostate cancer is often detected at the late stage of tumor development and it consistently remains a difficult clinical enigma. Therefore, the development of novel strategies for its diagnosis and treatment is essential.

Research development on Treatment of Prostate Cancer in Western Countries

Extensive studies have been carried out by scientists over the decades to understand how changes in the androgen receptor found in prostate tumor cells develop into a hormone-independent disease state as the disease progresses, and how these changes affect the binding of different molecules, including hormones. These insights have led to improved hormonal treatments for prostate cancer. Scientists generally assume that resistance of prostate cancer cells to hormone therapy can be explained by three general categories. 3, 4 The first includes DNA-based alternation such as amplification of the androgen receptor gene which occurs only in a small proportion of patients. 5 These mutations of androgen receptors alter the response of the receptors so that the ligands (hormones) behave as agonists. The second category happens in the majority of patients who have active androgen receptor signaling. The oncogene, such as HER-2/neu, can mediate an increase of mitogen-activated protein kinase signaling, which cause androgen-independent activation of the androgen receptor. 6 The third category of hormone resistance mechanism is based on the concept that the growth and survival promoting functions of the androgen receptors can be bypassed by alternative signaling pathways, such that the androgen receptor is no longer relevant to disease progression. 7 Gene expression profiles further indicate androgen receptor mRNAs are universally up-regulated in hormone-refractory human prostate cancer xenograft pairs and these are sufficient to convert prostate cancer growth from being hormone dependent to a hormone independent stage and are reliant on a functional ligand-binding domain. 8 These molecular determinants provide insight to the design of novel anti-androgens therapy.

Herbal Supplement Research on Prostate Cancer

The aforementioned factors which cause the development of androgen-independent prostate cancer progression are heterogeneous and multistage. The use of single-target western medicine may not be effective as treatment. On the contrary, combination therapies such as herbal remedies can act as an alternative and complementary approach for prostate cancer treatment since they may counteract different biological pathways that typically characterize cancer progression and thus impede success of cancer treatment. One example of a herbal supplement used in this area is Equiguard which combines nine herbs: Yin Yang Huo (Herba Epimedii ), Jin Yin Zi (Fructus Rosae Laevigatae ), Fu Pen Zi (Fructus Rubi ), Bu Gu Zhi (Fructus Psoraleae ), Ba Ji Tian (Radix Morindae Officinalis ), Tu Si Zi (Semen Cusctae ), Nu Zhen Zi (Fructus Ligustri Lucidi ), Wu Wei Zi (Fructus Schisandrae ) and Huang Qi (Radix Astragali ). According to Chinese medicinal principles, the kidney is the organ that maintains balance of the entire urological system. There are TCM dietary supplements like Equiguard that helps to restore the kidneys' yin and yang harmony, particularly for a kidney yang deficiency or a kidney qi deficiency. It is common to have occasional periods in our life where we have frequent, long, clear and colorless urine. But it usually goes back to normal after a short period of time. However, individuals will be considered as having a kidney yang deficiency or kidney qi deficiency when the above-mentioned symptoms persist for a considerable period of time. Preliminary in vitro studies were performed to test the effect and mechanism of Equiguard to modulate prostate growth and gene expression. These studies indicate that Equiguard can significantly reduce prostate cancer cell growth, either in androgen-dependent or in androgen-independent stage, by knocking down the cell cycle due to the down regulation of retinoblastoma protein Rb and inducing apoptosis via the release of cytochrome c,9increasing the expression of tumor suppressor p53,10 as well as suppressing androgen receptor gene expression. 11 These findings support the interpretations of Western medicine research in prostate tumor cell development and its treatment. Hence, Equiguard may be efficacious in treating androgen-dependent and androgen-independent prostate carcinoma. However, even though Equiguard suggests promising results in prostate cancer, its traditional roots should not be ignored. Further clinical research in individuals with prostate cancer and a kidney yang deficiency needs to be added to its in vitro results.

Conclusion

Over the last decade, there has been an expansion of our understanding of how the androgen receptor works during prostate cancer progression. It is hoped that this understanding will be exploitable in the design of novel anti-androgen therapy in order to achieve clinically significant results in the treatment of prostate cancer. Meanwhile, prostate cancer patients have increased their awareness of the use of herbal supplements due to the notion of chemoprevention. Indeed, because of the multistage and complex characteristics of prostate cancer, its progression might be best reduced or delayed through the use of herbal supplements such as Equiguard. Further research needs to be done in this area of cancer prevention.

References

1. National Cancer Institute. Cancer trends progress report - 2005 update. http://progressreport.cancer.gov/
2. Feldman, B.J. et al. The development of androgen-independent prostate cancer. Nat. Rev. Cancer 1, 34-35 (2001).
3. Gelmann, E.P. Molecular biology of the androgen receptor. J. Clin. Oncol. 20, 3001-3015 (2002).
4. Taplin , M.E.et al. Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist. Cancer Res. 59, 2511-2515 (1999).
5. Visakorpi, T. et al.In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nat. Genet. 9, 401-406 (1995).
6. Craft, N. et al. A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase. Nat. Med. 5, 280-285 (1999).
7. Raffo, A.J. et al. Overexpression of bcl-2 protects prostate cancer cells from apoptosis in vitro and confers resistance to androgen depletion in vivo. Cancer Res. 55, 4438-4445 (1995).
8. Chen, C.D. et al. Molecular determinants of resistance to antiandrogen therapy. Nat. Med. 10, 33-39 (2004)
9. Lu, X. et al. Equiguard suppresses androgen-dependent LNCaP prostate cancer cell proliferation by targeting cell cycle control via down regulation of the retinoblastoma protein Rb and induction of apoptosis via the release of cytochrome c. Int. J. Oncol. 25, 1801-1807 (2004). (If you would like a reprint of this article, please email us.)
10. Lu, X. et al. Inhibition of proliferation and expression of AR/PSA by herbal supplement Equiguard in LNCaP cells cultured in androgen-proficient FBS and androgen-deficient charcoal-stripped FBS is correlated with increased Serine-15 phosphorylation of the tumor suppressor gene p53 . Anticancer Res. 23 , 2489 - 2498 (2003). (If you would like a reprint of this article, please email us.)
11. Hsieh, T.C. et al. Effects of herbal preparation Equiguard on hormone-responsive and hormone-refractory prostate carcinoma cells: mechanistic studies. Int. J. Oncol. 20, 681-689 (2002). (If you would like a reprint of this article, please email us.)

Compiled and edited by:

Jennifer Eagleton, BA, MA (Asian Studies), Integrated Chinese Medicine Holdings Ltd. Stan Man, Integrated Chinese Medicine Holdings Ltd.