Inhibitory effects of crude alpha-mangostin, a xanthone derivative, on two different categories of colon preneoplastic lesions induced by 1, 2-dimethylhydrazine in the rat.
The purpose of this study was to examine whether crude alpha-mangostin (a major xanthone derivative in mangosteen pericarp (Garcinia mangostana)) has short-term chemopreventive effects on putative preneoplastic lesions involved in rat colon carcinogenesis. The crude preparation was obtained by simple recrystallization of an ethylacetate extract of mangosteen pericarps. A total of 33 five-week-old male F344 rats were randomly divided into 5 experimental groups. Rats in groups 1-3 were given a subcutaneous injection of 1,2-dimethylhydrazine (DMH)(40 mg/kg body weight) once a week for 2 weeks. Starting one week before the first injection of DMH, rats in groups 2 and 3 were fed a diet containing 0.02% and 0.05% crude alpha-mangostin, respectively, for 5 weeks. Rats in group 4 also received the diet containing 0.05% crude alpha-mangostin, while rats in group 5 served as untreated controls. The experiment was terminated 5 weeks after the start. Dietary administration of crude alpha-mangostin at both doses significantly inhibited the induction and/or development of aberrant crypt foci (ACF) (P<0.05 for 0.02% crude alpha-mangostin, P<0.01 for 0.05% crude alpha-mangostin), when compared to the DMH-treated group (group 1). Moreover, treatment of rats with 0.05% crude alpha-mangostin significantly decreased dysplastic foci (DF) (P<0.05) and beta-catenin accumulated crypts (BCAC) (P<0.05), to below the group 1 values. The proliferating cell nuclear antigen (PCNA) labeling indices of colon epithelium and focal lesions in groups 2 and 3 were also significantly lower than in group 1 and this effect occurred in a dose dependent manner of the crude alpha-mangostin. This finding that crude alpha-mangostin has potent chemopreventive effects in our short-term colon carcinogenesis bioassay system suggests that longer exposure might result in suppression of tumor development.
Nabandith
Viengvansay
V
Tumor Pathology Division, Faculty of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
Suzui
Masumi
M
Morioka
Takamitsu
T
Kaneshiro
Tatsuya
T
Kinjo
Tatsuya
T
Matsumoto
Kenji
K
Akao
Yukihiro
Y
Iinuma
Munekazu
M
Yoshimi
Naoki
N
D019813:1,2-Dimethylhydrazine; D000818:Animals; D018890:Chemoprevention; D003110:Colonic Neoplasms / Q000517:prevention & control*; D029762:Garcinia mangostana; D007150:Immunohistochemistry; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011230:Precancerous Conditions / Q000188:drug therapy* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D044004:Xanthones / Q000494:pharmacology* / Q000627:therapeutic use
D010936:Plant Extracts; D044004:Xanthones; D019813:1,2-Dimethylhydrazine; C021053:mangostin