Two birds, one stone: hesperetin alleviates chemotherapy-induced diarrhea and potentiates tumor inhibition.

Two birds, one stone: hesperetin alleviates chemotherapy-induced diarrhea and potentiates tumor inhibition. Oncotarget. 2018 Jun 15;9(46):27958-27973 Authors: Yu Y, Kong R, Cao H, Yin Z, Liu J, Nan X, Phan AT, Ding T, Zhao H, Wong STC Abstract Chemotherapy-induced diarrhea (CID), with clinical high incidence, adversely affects the efficacy of cancer treatment and patients' quality of life. Our study demonstrates that the citrus flavonoid hesperetin (Hst) has a superior potential as a new agent to prevent and alleviate CID. In the animal model for irinotecan (CPT-11) induced CID, Hst could selectively inhibit intestinal carboxylesterase (CES2) and thus reduce the local conversion of CPT-11 to cytotoxic SN-38 which causes intestinal toxicity. Oral administration of Hst manifested an excellent anti-diarrhea efficacy, prohibiting 80% of severe and 100% of mild diarrhea in the CPT-11 administered tumor-bearing mice. In addition, a significant attenuation of intestinal inflammation contributed to the anti-diarrhea effect of Hst. Moreover, Hst was found to work synergistically with CPT-11 in tumor inhibition by suppressing the tumor's STAT3 activity and recruiting tumoricidal macrophages into the tumor microenvironment. The anti-intestinal inflammation and anti-STAT3 properties of Hst would contribute its broad benefits to the management of diarrhea caused by other chemo or targeted agents, and more importantly, enhance and reinforce the an...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research