TY - JOUR
T1 - Chemoprevention of colon carcinogenesis by oleanolic acid and its analog in male F344 rats and modulation of COX-2 and apoptosis in human colon HT-29 cancer cells
AU - Janakiram, Naveena B.
AU - Indranie, Cooma
AU - Malisetty, Swamy V.
AU - Jagan, Patlolla
AU - Steele, Vernon E.
AU - Rao, Chinthalapally V.
PY - 2008/9
Y1 - 2008/9
N2 - Purpose. To assess the chemopreventive effect of oleanolic acid (ONA) and its synthetic analog 18α-olean-12-ene-3β-23,28-triol (OT) on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in F344 rats and understand anti-inflammatory properties and apoptosis effects in HT29 colon cancer cells and Raw 264.7 macrophage cell lines. Methods. Five week-old male F344 rats were fed a control diet or experimental diets containing two doses of ONA (750 and 1,500 ppm) and OT (250 and 500 ppm). After 1 week, all animals were s.c. injected with AOM (15 mg/kg body weight, once weekly for 2 weeks). At 14 weeks of age, all rats were killed and colons were evaluated for ACF. Cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) expressions and apoptosis were assessed in cell lines exposed to OT using western blots and 4',6-diamidino-2-phenylindole staining. Results. Administration of ONA and OT inhibited mean colonic ACF and multi-crypt AC/foci in a dose dependent manner (p < 0.001-0.0001). OT blocked the COX-2 expression induced by phorbol 12-myristate 13-acetate in a dose-dependent manner and induced apoptosis in HT-29 cancer cells, and suppressed iNOS activation in RAW264.7 macrophages. Conclusions. ONA and OT possess chemopreventive activity against colon carcinogenesis in rat and OT inhibits the COX-2 and iNOS and induces apoptosis in cell lines.
AB - Purpose. To assess the chemopreventive effect of oleanolic acid (ONA) and its synthetic analog 18α-olean-12-ene-3β-23,28-triol (OT) on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in F344 rats and understand anti-inflammatory properties and apoptosis effects in HT29 colon cancer cells and Raw 264.7 macrophage cell lines. Methods. Five week-old male F344 rats were fed a control diet or experimental diets containing two doses of ONA (750 and 1,500 ppm) and OT (250 and 500 ppm). After 1 week, all animals were s.c. injected with AOM (15 mg/kg body weight, once weekly for 2 weeks). At 14 weeks of age, all rats were killed and colons were evaluated for ACF. Cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) expressions and apoptosis were assessed in cell lines exposed to OT using western blots and 4',6-diamidino-2-phenylindole staining. Results. Administration of ONA and OT inhibited mean colonic ACF and multi-crypt AC/foci in a dose dependent manner (p < 0.001-0.0001). OT blocked the COX-2 expression induced by phorbol 12-myristate 13-acetate in a dose-dependent manner and induced apoptosis in HT-29 cancer cells, and suppressed iNOS activation in RAW264.7 macrophages. Conclusions. ONA and OT possess chemopreventive activity against colon carcinogenesis in rat and OT inhibits the COX-2 and iNOS and induces apoptosis in cell lines.
KW - COX-2
KW - Chemoprevention
KW - Colon cancer
KW - Triterpenoids
KW - iNOS
UR - http://www.scopus.com/inward/record.url?scp=49549117555&partnerID=8YFLogxK
U2 - 10.1007/s11095-008-9582-7
DO - 10.1007/s11095-008-9582-7
M3 - Article
C2 - 18408893
AN - SCOPUS:49549117555
SN - 0724-8741
VL - 25
SP - 2151
EP - 2157
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 9
ER -