Journal article
Two birds, one stone: hesperetin alleviates chemotherapy-induced diarrhea and potentiates tumor inhibition
Oncotarget, Vol.9(46), pp.27958-27973
06/15/2018
DOI: 10.18632/oncotarget.24563
PMCID: PMC6021345
PMID: 29963254
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.
Details
- Title: Subtitle
- Two birds, one stone: hesperetin alleviates chemotherapy-induced diarrhea and potentiates tumor inhibition
- Creators
- Yaping Yu - Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medicine, Houston, TX, 77030, USARen Kong - Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medicine, Houston, TX, 77030, USAHuojun Cao - Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medicine, Houston, TX, 77030, USAZheng Yin - Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medicine, Houston, TX, 77030, USAJiyong Liu - Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medicine, Houston, TX, 77030, USAXiang Nan - Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medicine, Houston, TX, 77030, USAAlexandria T Phan - Cancer Treatment Centers of America at South Eastern Regional Center, Atlanta, GA, 30265, USATian Ding - Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medicine, Houston, TX, 77030, USAHong Zhao - Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medicine, Houston, TX, 77030, USAStephen T.C Wong - Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medicine, Houston, TX, 77030, USA
- Resource Type
- Journal article
- Publication Details
- Oncotarget, Vol.9(46), pp.27958-27973
- DOI
- 10.18632/oncotarget.24563
- PMID
- 29963254
- PMCID
- PMC6021345
- NLM abbreviation
- Oncotarget
- ISSN
- 1949-2553
- eISSN
- 1949-2553
- Publisher
- Impact Journals LLC
- Language
- English
- Date published
- 06/15/2018
- Academic Unit
- Anatomy and Cell Biology; Endodontics; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984065804602771
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