Insulin-like growth factors are more effective than progastrin in reversing proapoptotic effects of curcumin: critical role of p38MAPK.

American Journal of Physiology. Gastrointestinal and Liver Physiology
P SinghThomas G Wood

Abstract

Progastrin and insulin-like growth factors (IGFs) stimulate hyperproliferation of intestinal epithelial cells (IECs) via endocrine/paracrine routes; hyperproliferation is a known risk factor for colon carcinogenesis. In the present study, inhibitory potency of curcumin in the presence or absence of progastrin and/or IGF-II was examined. Progastrin and IGF-II significantly increased proliferation of an immortalized IEC cell line, IEC-18, whereas curcumin decreased the proliferation in a dose-dependent manner. IGF-II was significantly more effective than progastrin in reversing antiproliferative effects of curcumin and reversed proapoptotic effects of curcumin by >80%; progastrin was relatively ineffective toward reversing proapoptotic effects of curcumin. IEC-18 clones were generated to overexpress either progastrin (IEC-PG) or hIGF-II (IEC-IGF). Proliferation of IEC-PG and IEC-IGF clones was increased, compared with that of control clones. Curcumin significantly reduced proliferation of IEC-PG, but not IEC-IGF, clones. Similarly, a human colon cancer cell line, Caco-2 (which expresses autocrine IGF-II), was relatively resistant to inhibitory effects of curcumin. However, Caco-2 cells treated with anti-IGF-II-antibodies were ren...Continue Reading

References

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