Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury.
Gastrointestinal (GI) mucosal damage is a devastating adverse effect of radiation therapy. We have recently reported that expression of Dclk1, a Tuft cell and tumor stem cell (TSC) marker, 24h after high dose total-body gamma-IR (TBI) can be used as a surrogate marker for crypt survival. Dietary pectin has been demonstrated to possess chemopreventive properties, whereas its radioprotective property has not been studied. The aim of this study was to determine the effects of dietary pectin on ionizing radiation (IR)-induced intestinal stem cell (ISC) deletion, crypt and overall survival following lethal TBI. C57BL/6 mice received a 6% pectin diet and 0.5% pectin drinking water (pre-IR mice received pectin one week before TBI until death; post-IR mice received pectin after TBI until death). Animals were exposed to TBI (14 Gy) and euthanized at 24 and 84h post-IR to assess ISC deletion and crypt survival respectively. Animals were also subjected to overall survival studies following TBI. In pre-IR treatment group, we observed a three-fold increase in ISC/crypt survival, a two-fold increase in Dclk1+ stem cells, increased overall survival (median 10d vs. 7d), and increased expression of Dclk1, Msi1, Lgr5, Bmi1, and Notch1 (in small intestine) post-TBI in pectin treated mice compared to controls. We also observed increased survival of mice treated with pectin (post-IR) compared to controls. Dietary pectin is a radioprotective agent; prevents IR-induced deletion of potential reserve ISCs; facilitates crypt regeneration; and ultimately promotes overall survival. Given the anti-cancer activity of pectin, our data support a potential role for dietary pectin as an agent that can be administered to patients receiving radiation therapy to protect against radiation-induces mucositis.
Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America; Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, United States of America; The Peggy and Charles Stephenson Cancer Center, Oklahoma City, Oklahoma, United States of America.
Sripathi M
SM
Sureban
Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America; Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, United States of America.
Randal
R
May
Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
Dongfeng
D
Qu
Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
Parthasarathy
P
Chandrakesan
Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
Nathaniel
N
Weygant
Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America; The Peggy and Charles Stephenson Cancer Center, Oklahoma City, Oklahoma, United States of America.
Naushad
N
Ali
Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
Stan A
SA
Lightfoot
Department of Biostatistics and Epidemiology, College of Public Health, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
Kai
K
Ding
Department of Molecular & Integrative Physiology, The University of Kansas, Kansas City, Kansas, United States of America.
Shahid
S
Umar
COARE Biotechnology Inc., Oklahoma City, Oklahoma, United States of America.
Michael J
MJ
Schlosser
Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America; Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, United States of America; The Peggy and Charles Stephenson Cancer Center, Oklahoma City, Oklahoma, United States of America.
Courtney W
CW
Houchen
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D019587:Dietary Supplements / Q000032:analysis; D000089742:Doublecortin-Like Kinases; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D052016:Mucositis / Q000178:diet therapy / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D010368:Pectins / Q000008:administration & dosage* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000178:diet therapy / Q000473:pathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D016019:Survival Analysis; D014916:Whole-Body Irradiation
D011837:Radiation-Protective Agents; D010368:Pectins; D000089742:Doublecortin-Like Kinases; C485525:Dclk1 protein, mouse; D017346:Protein Serine-Threonine Kinases