Chemopreventive effects of 13alpha,14alpha-epoxy-3beta-methoxyserratan-21beta-ol (PJJ-34), a serratane-type triterpenoid, in a rat multi-organ carcinogenesis bioassay.
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.
Doi
Kenichiro
K
Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. kenchan@mx5.suisui-w.ne.jp
Sakai
Kuniyoshi
K
Tanaka
Reiko
R
Toma
Kaori
K
Yamaguchi
Takashi
T
Wei
Min
M
Fukushima
Shoji
S
Wanibuchi
Hideki
H
D000818:Animals; D001681:Biological Assay; D019938:Cyclin D1 / Q000378:metabolism; D004852:Epoxy Compounds / Q000627:therapeutic use*; D005982:Glutathione Transferase / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008297:Male; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D015996:Survival Rate; D014315:Triterpenes / Q000627:therapeutic use*
C436351:13alpha,14alpha-epoxy-3beta-methoxyserratan-21beta-ol; C530106:Ccnd1 protein, rat; D004852:Epoxy Compounds; D018809:Proliferating Cell Nuclear Antigen; D014315:Triterpenes; D019938:Cyclin D1; D005982:Glutathione Transferase