A novel serratane-type
triterpenoid,
13alpha,14alpha-epoxy-3beta-methoxyserratan-21beta-ol (PJJ-34) derived from cuticles of Picea jezoensis Carr. var. jezoensis, has proved to be highly effective at suppressing
carcinogenesis both in vitro and in vivo. To investigate possible anti-carcinogenic efficacy at the whole-body level, male Fischer 344 rats were subjected to an established rat multi-organ
carcinogenesis bioassay (DMBDD model). After initiation with five
carcinogens, groups 1-3 (20 in each) were intragastrically (i.g.) administered PJJ-34 dissolved in 1 ml of 0.5% CMC (5 times/week) at doses of 0, 5 and 10mg/kg
body weight (b.w.), respectively, until the end of week 30. PJJ-34 did not show apparent toxicity. Incidences of
adenomas (100-->75%) and
carcinomas (63-->30%) in the lung were significantly decreased in the 5mg/kg b.w. group, and multiplicity of alveolar
hyperplasias and total lung
tumors (adenomas+carcinomas) were significantly reduced by both 5 and 10mg/kg. The incidence of
colorectal tumors was also significantly decreased in the 10mg/kg group (63-->28%) along with the multiplicity. Rat liver pre-neoplastic lesions,
glutathione S-transferase placental form (GST-P) foci, and
tumor development in the other organs were not affected. Immunohistochemical indices for
proliferating cell nuclear antigen (
PCNA) and
cyclin D1 in normal alveolar epithelium of the lung were significantly suppressed at both doses. In conclusion, PJJ-34 is chemopreventive against lung and colon
carcinogenesis without exerting apparent toxicity, and suppression of cell proliferation could play a key role in the underlying mechanisms.