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Prevention Research 9: Prevention of Breast, Prostate, and Skin Cancer

Abstract #4277

Chemoprevention of MNU-induced mammary tumorigenesis in SD-rats by 1SY16 isolated from Agaricus blazei Murill K

Kanazawa University, Kanazawa, Japan

Previously, we have demonstrated that a low molecular fraction 1SY16 (500 dalton) isolated from Agaricus blazeiMurill K was found to be a very effective chemopreventive agent against NNK-, urethane or AOM-induced pulmonary adenoma, or colon ACF and colon carcinoma. Furthermore, chemopreventive effects of 1SY16 was closely associated with inhibition of cell cycle gene during the tumorigenesis. Present study was undertaken to evaluate whether chemopreventive effects of 1SY16 can be also demon-strated in MNU-induced mammary tumorigenesis. For the 1SY16 dose responsive effects were determined by treating 4 experimental groups, consisted of control, experimental group each receiving a single daily dose of 100, 200, or 400 mg 1SY16/kg bw for 15 days, immediately following a single administration of MNU via tail vein. To determine the stage specific chemopreventive effects of 1SY16 during the course of MNU-induced mammary tumorigenesis, 5 experimental groups, consisting of control, and 1SY16 treatment groups (200mg 1SY16/kg bw./day for the first, 2^nd, 3^rd, and 4^th months after initiation. The results demonstrated that mammary tumor incidence in the 100, 200, or 400mg 1SY16/kg b.w./15 days groups were 22 (p<0.05), 43 (p<0.001), and 55 (p<0.01)%, respectively. Concomitantly, dose dependent inhibition was also reflected in both cyclin D₁ expression (90, 75, and 58% of control) and PCNA expression (92,73, and 68% of control) in mammary tumors. Chemopreventive effects of 1SY16 at different stages of tumorigenesis were 60 (p<0.05), 65 (p<0.05), 54 (p<0.05), and 28 (0.01)% of control, respectively. Furthermore, the mean mammary tumor mass during different stages of mammary tumorigenesis were 26(p<0.05), 46, 54, and 14(p<0.05)%, respectively. In conclusion, from these experimental results together with previously published data demonstrated that 1SY16 appears to be a very potent multipotential chemopreventive agent.