Achaete-scute homolog-1 and Notch in lung neuroendocrine development and cancer

The modifying effects of dietary feeding of extract of leaves of ginkgo (Ginkgo biloba) (EGb) and bilobalide isolated from EGb on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in male F344 rats. We also assessed the effects of EGb and bilobalide on proliferating cell nuclear antigen (PCNA) index in ‘normal-appearing’ crypts and activities of detoxifying enzymes of cytochrome P450 (CYP), glutathione S-transferase (GST) and quinine reductase (QR) activity in the liver. To induce ACF, rats were given two weekly subcutaneous injections of AOM (20 mg/kg body wt). They also received the experimental diets containing EGb (50 or 500 ppm) and bilobalide (15 or 150 ppm) for 4 weeks, starting 1 week before the first dosing of AOM. AOM exposure produced a substantial number of ACF (106±10) at the end of the study (week 4). Dietary administration of EGb and bilobalide caused significant reduction in the frequency of ACF: 50 ppm EGb, 73±17 (31% reduction, P<0.001); 500 ppm EGb, 56±13 (47% reduction, P<0.001); 15 ppm bilobalide, 79±17 (25% reduction, P<0.01); and 150 ppm bilobalide, 71±30 (33% reduction, P<0.01). Immunohistochemically, EGb or bilobalide administration significantly lowered PCNA index in normal-appearing crypts. Feeding with EGb or bilobalide increased activities of CYP as well as GST and QR in the liver. These findings might suggest possible chemopreventive ability of EGb or bilobalide, through alterations in cryptal cell proliferation activity and drug metabolizing enzymes' activities, in colon tumorigenesis.