Chemopreventive effects of a serratane-type triterpenoid, 3alpha-methoxyserrat-14-en-21beta-ol (PJ-1), against rat lung carcinogenesis.
Our efforts to search for cancer-chemopreventive agents have been focused on constituents from materials of trees such as leaves and bark as waste in the forestry industry. Cancer-chemopreventive effects of a serratane-type triterpenoid from the bark of Picea jezoensis, 3alpha-methoxyserrat-14-en-21beta-ol (PJ-1), were here examined in a revised rat multi-organ carcinogenesis (DMBDD) model. Male 6-week-old F344 rats received combined treatment with five different carcinogens and starting 1 week thereafter were administered PJ-1 at a dose of 2mg/kg or 6mg/kg body wt i.g. (five times/week) or the vehicle as a control (1ml of 0.5% CMC). At the termination at week 30, significant decrease of adenomas (P<0.01) and total tumors (P<0.01) and a trend for reduction of adenocarcinoma multiplicity in the lung were observed, but without any modulating influence in other major organs. The cell proliferation indices in the lungs tended to be decreased in the PJ-1 administered groups, with apparent induction of CYP2B1/2 mRNA expression to recover the values observed in non-initiated controls. These results indicate that PJ-1 exerts cancer-chemopreventive effects on rat lung carcinogenesis after multi-organ initiation.
Yamaguchi
Chiharu
C
Department of Medical Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Wanibuchi
Hideki
H
Kakehashi
Anna
A
Tanaka
Reiko
R
Fukushima
Shoji
S
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D007527:Isoenzymes / Q000096:biosynthesis; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014315:Triterpenes / Q000627:therapeutic use*
C418725:3-alpha-methoxyserrat-14-en-21-beta-yl formate; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D007202:Indicators and Reagents; D007527:Isoenzymes; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D014315:Triterpenes; D012313:RNA; D003577:Cytochrome P-450 Enzyme System