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 az...

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Bibliographic Details
Published in:Cancer biology & therapy 2012-02, Vol.13 (3), p.130-137
Main Authors: Rinella, Erica, Bankaitis, Eric, Threadgill, David
Format: Article
Language:English
Subjects:
AG1478
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Antineoplastic Agents - toxicity
Azoxymethane
Binding
Biology
Bioscience
Calcium
Calcium - pharmacology
Calcium - therapeutic use
Calcium - toxicity
Cancer
Cell
Cell Line, Tumor
Cell Proliferation - drug effects
Cell Survival - drug effects
colon cancer
Colonic Neoplasms - chemically induced
Colonic Neoplasms - drug therapy
Colonic Neoplasms - pathology
Cycle
Dietary Supplements
Drug Screening Assays, Antitumor
Drug Synergism
EGFR
Female
Humans
Landes
Male
MAP Kinase Signaling System - drug effects
Mice
Mice, Inbred C57BL
mouse models
Organogenesis
Proteins
Quinazolines - pharmacology
Quinazolines - therapeutic use
Quinazolines - toxicity
Random Allocation
Receptor, Epidermal Growth Factor - antagonists & inhibitors
Research Paper
therapy
toxicity
Tumor Burden - drug effects
Tyrphostins - pharmacology
Tyrphostins - therapeutic use
Tyrphostins - toxicity
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Summary: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.
ISSN:1538-4047
1555-8576
DOI:10.4161/cbt.13.3.18690