Dietary calcium supplementation enhances efficacy but also toxicity of EGFR inhibitor therapy for colon cancer.
The inverse correlation between levels of dietary calcium and colorectal cancer (CRC) incidence has been extensively investigated. However, the impact of supplemental calcium on cancer therapy remains unknown. We used four models of CRC, Caco-2 and HCT116 human cancer cell lines and Apc (Min/+)  and azoxymethane carcinogen-induced mouse models, to investigate the impact of a western-style diet low in calcium (0.05%) vs. a similar diet but supplemented with calcium (5%) on therapeutic targeting of the epidermal growth factor receptor (EGFR). We found that calcium supplementation combined with pharmacologic blockade of EGFR results in an additive effect on tumor growth inhibition in all models. Unexpectedly, the combined use of dietary calcium supplementation and EGFR inhibitors also resulted in elevated toxicity suggesting that careful consideration be given when combining dietary supplements with prescribed cancer therapies.
Department of Genetics, Curriculum in Genetics and Molecular Biology, Lineberger Cancer Center and Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
Erica S
ES
Rinella
Eric D
ED
Bankaitis
David W
DW
Threadgill
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D001397:Azoxymethane; D002118:Calcium / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D019587:Dietary Supplements; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D011897:Random Allocation; D047368:Tumor Burden / Q000187:drug effects; D020032:Tyrphostins / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity
D000970:Antineoplastic Agents; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; D066246:ErbB Receptors; D001397:Azoxymethane; D002118:Calcium