Issues

Estrogen plays an important role in colon tumorigenesis. Studies show that selective estrogen receptor modulators, such as raloxifene, suppress tumor growth. However, gonadorelin, possessing estrogen-modulatory effects, has not been tested on tumor growth. The preventive effects of raloxifene and gonadorelin were studied in female Apc^Min/+ mouse intestinal tumorigenesis. Mice treated with raloxifene and gonadorelin showed colon tumor inhibition of 80% and 75%, respectively. As well, these treated tumors showed significantly increased natural killer (NK) cells and chemokines required for NK cells as well as decreased inflammatory genes and cancer stem-like cells (Lgr 5, EpCAM, CD44/CD24). The cover micrograph (60×) depicts the immunohistofluorescence of NK cell receptors (red) and nuclei (blue) in intestinal tumors from Apc^Min/+ mice treated with raloxifene and gonadorelin (∼ 4-fold increase; P < 0.002). Both drugs were effective in suppressing tumor growth albeit with different mechanisms. These observations show that either suppression of endogenous estrogen levels (by gonadorelin) or modulation of estrogen receptor (by raloxifene) dramatically suppresses small intestinal and colonic tumor formation in female Apc^Min/+ mice and supports the concept of chemoprevention by these agents in reducing endogenous levels of estrogen or modulating ER signaling. See article by Janakiram and colleagues (beginning on page 300) for more information.