Berberine enhances chemosensitivity to irinotecan in colon cancer via inhibition of NF-κB

Abstract

Previous studies have shown that irinotecan (CPT-11) impairs chemotherapy-induced apoptosis by activating nuclear factor-κB (NF-κB) and a number of strategies have been employed to augment chemosensitivity through the suppression of NF-κB activation. Berberine, a botanical alkaloid, was reported to enhance chemosensitivity to 5-fluorouracil and doxorubicin by suppressing NF-κB activation. In the present study, the effect of berberine on CPT-11-induced apoptosis was investigated through the inhibition of NF-κB. Inhibition of NF-κB activation by p65 small interfering RNA was shown to potentiate apoptosis induced by CPT-11. Berberine suppressed CPT-11-induced NF-κB activation in a dose-dependent manner and enhanced chemosensitivity to CPT-11 by down-regulating NF-κB activation of antiapoptotic genes, c-IAP1, c-IAP2, survivin and Bcl-xL. The current observations indicate that berberine inhibits NF-κB activation and may be used to enhance CPT-11-induced apoptosis in colon cancer.