Abstract 5581: Korean Angelica gigas Nakai (AGN) and Oriental herbal cocktail ka-mi-kae-kyuk-tang (KMKKT) inhibit prostate carcinogenesis in TRAMP model

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL The ka-mi-kae-kyuk-tang (KMKKT) is a formula of ten Oriental herbs containing Korean Angelica gigas Nakai (AGN) root. Previous studies by our collaborative team found that the KMKKT ethanol extract exerted anti-angiogenesis, apoptosis and anti-metastasis in vitro and in vivo (carcinogenesis 2006). We also showed that AGN extract suppressed DU-145 & PC-3 xenograft growth (Am J Chin Med 1009). In the present study, we used the transgenic adenocarcinoma of the mouse prostate (TRAMP) spontaneous primary carcinogenesis model to establish the chemoprevention efficacy of KMKKT and AGN and to explore cellular and molecular correlates of the in vivo anti-cancer effects. Male C57BL6 TRAMP mice were given a daily gavage (5 times per wk, 5 mg/mouse) as KMKKT and AGN beginning at 8 weeks of age (1% Tween-80 as vehicle n=13; KMKKT n=14; AGN n=17). We treated wild-type littermates also with KMKKT and AGN. All mice were terminated at 24 weeks of age, unless earlier euthanasia was necessitated by large tumor size. The results show that the genitourinary (GU) tract weight was decreased in both KMKKT (66.4%) and AGN (57.6%) treated groups compared to vehicle group (100%). The dorsal-lateral prostate (DLP) weight was significantly lower in KMKKT and AGN groups compared to control group (P=0.02), with no difference found in the wild-type mice cohorts. In TRAMP and wild-type mice that received KMKKT and AGN vs. vehicle, there is no significant difference of the body weight and main organs (liver and kidney) (P>0.05). Additionally, macroscopical prostate tumors were found 46.2% (6/13) in control group, but just 14.3% (2/14) and 17.6% (3/17) in KMKKT and AGN group (Chi-square analysis P=0.07 and P=0.09). The average tumor burden was 0.81g/mouse in control group, 0.27 and 0.12 g/mouse in KMKKT and AGN group, respectively. All these macroscopical tumors are T-antigen (+), synaptophysin(+), androgen-receptor(−) and E-cadherin(−) poorly differentiated neuro-endocrine carcinoma (NECa). Furthermore, KMKKT and AGN-treated NECa contained lower basic fibroblast growth factor (bFGF) detectable by WB, antibody array and IHC. Decursinol, the hydrolysis product of decursin and DA was detectable in the plasma of AGN-treated mice. In summary, results from this pilot study indicate that oral administration of KMKKT and AGN may inhibit prostate primary carcinogenesis in the TRAMP model. Additional chemoprevention studies are merited. [Grant support: NCCAM 1R21AT005383, NCI R01CA136953, R01CA126880 and Korean KOSEF-MEST No. 2009-0063466]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5581. doi:10.1158/1538-7445.AM2011-5581