Two birds, one stone: Hesperetin alleviates chemotherapyinduced diarrhea and potentiates tumor inhibition

Yaping Yu, Ren Kong, Huojun Cao, Zheng Yin, Jiyong Liu, Xiang Nan, Alexandria T. Phan, Tian Ding, Hong Zhao, Stephen T.C. Wong

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 anti-tumor effects of these agents, to improve patient outcomes.

Original languageEnglish (US)
Pages (from-to)27958-27973
Number of pages16
JournalOncotarget
Volume9
Issue number46
DOIs
StatePublished - Jun 15 2018

Keywords

  • Chemotherapy-induced diarrhea
  • Hesperetin
  • Human intestinal carboxylesterase (CES2)
  • Macrophage
  • STAT3

ASJC Scopus subject areas

  • Oncology

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