Abstract. The Equiguard is a dietary supplement comprised of standardized extracts from nine herbs, respectively, Herba epimedium brevicornum Maxim (stem and leaves), Radix morindae officinalis (root), Fructus rosa laevigatae michx (fruit), Rubus chingii Hu (fruit), Schisandra chinensis (Turz.) Baill (fruit), Ligustrum lucidum Ait (fruit), Cuscuta chinensis Lam (seed), Psoralea corylifolia L. (fruit), and Astragalus membranaceus (Fisch.) Bge (root). This proprietary product, formulated according to Chinese traditional medicinal concepts, is aimed at restoring harmony in the ‘primordial (original) ying-yang’ of the kidney, an organ which Chinese medicinal principles consider to be vital for invigorating as well as maintaining balance of the entire urological system. As the prostate is an integral component of the urological system, we performed in vitro studies to test the effects of ethanol extracts of Equiguard to modulate prostate growth and gene expression. These studies used prostate cancer cells mimicking the androgen-dependent (AD) and androgen-independent (AI) states of prostate carcinogenesis. Results show that Equiguard significantly reduced cancer cell growth, induced apoptosis, suppressed expression of the androgen receptor (AR) and lowered intracellular and secreted prostate specific antigen (PSA), and almost completely abolished colony forming abilities of prostate cancer cells. These data support the inter- pretation that this herbal formulation contains ingredients that collectively may be efficacious in preventing or treating AD and AI prostate carcinoma. The anti-prostatic activities of Equiguard may stem from its complex composition capable of targeting multiple signal transduction/metabolic pathways, to effectively correct, counteract or circumvent the impaired or dysfunctional mechanisms accompanying different stages of prostate carcinogenesis. Introduction Prostate cancer (CaP) is the most commonly diagnosed neo- plasm and produces the second-highest cancer mortality in U.S. males. Approximately 179,000 new cases were reported in 1999, with 37,000 deaths resulting from the disease (1,2). An upward trend in these statistics is expected due in part to a projected increase in life expectancy among adult males and wider implementation of PSA screening for CaP in its early stages (1,2). In individuals diagnosed with CaP, initially the cancer cells are slow growing and androgen-dependent (ADPc); ADPc patients may remain subclinical for an extended period of time. Ultimately the disease progresses to an androgen-independent state (AIPc), characterized by greater proliferation of cells, lack of responsiveness to androgen blockade, and high fatalities (2-5). The mainstay for localized CaP includes radical prostectomy, radiation therapy, and hormonal modalities such as androgen deprivation using physical or chemical measures. These first-line treatments often result in positive responses in the majority of patients. However, relapse occurs with predictable frequency in a significant percentage of treated individuals; the recurrence is often accompanied by emergence of hormone-insensitive and -refractory clones. Expansion of these clones can result in establishment of hormone-insensitive states, which frequently will be rapidly followed by metastasis to sites beyond the confines of the gland and are not readily treatable (6). Thus, what is urgently needed are easily compliant preventive and treatment strategies. Research directed towards mechanistic understanding of such new strategies is also imperative. Epidemiologic studies have consistently shown that age- adjusted incidence and mortality rates for clinical CaP display significant geographic variations and marked differences among various ethnic/racial groups. Genetic and epigenetic factors and their interplays contribute to the observed variable incidence (7,8). Diet and specific nutritional ingredients have been proposed to exert promoting as well as protecting roles in the progression and establishment of CaP clinically (9-13). Culture and regional customs, such as food and other lifestyle INTERNATIONAL JOURNAL OF ONCOLOGY 20: 681-689, 2002 681 Effects of herbal preparation Equiguard on hormone-responsive and hormone-refractory prostate carcinoma cells: Mechanistic studies TZE-CHEN HSIEH 1,2 , XIAOHUA LU 1 , JUNQIAO GUO 1 , WEN XIONG 1 , JAN KUNICKI 2 , ZBIGNIEW DARZYNKIEWICZ 2 and JOSEPH M. WU 1,2 1 Department of Biochemistry and Molecular Biology, 2 Brander Cancer Research Institute, New York Medical College, Valhalla, NY 10595, USA Received December 6, 2001; Accepted February 1, 2002 _________________________________________ Correspondence to: Dr Joseph M. Wu, Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA E-mail: joseph_wu@nymc.edu Key words: Equiguard, prostate carcinoma