Folic Acid Supplementation Promotes Mammary Tumor Progression in a Rat Model

Autor: Kyoung-Jin Sohn, Shaidah Deghan Manshadi, Richard Renlund, Alan Medline, Young-In Kim, Lisa Ishiguro, Ruth Croxford
Rok vydání: 2014
Předmět:
Receptor
ErbB-2
Gene Expression
lcsh:Medicine
medicine.disease_cause
Rats
Sprague-Dawley
0302 clinical medicine
Breast Tumors
lcsh:Science
Receptor
bcl-2-Associated X Protein
0303 health sciences
Mammary tumor
Multidisciplinary
biology
Cancer Risk Factors
Obstetrics and Gynecology
food and beverages
Animal Models
Vitamins
Neoplasm Proteins
Tumor Burden
3. Good health
Oncology
Nutritional Correlates of Cancer
030220 oncology & carcinogenesis
Disease Progression
Medicine
Experimental pathology
Female
Poly(ADP-ribose) Polymerases
Cancer Prevention
Research Article
medicine.medical_specialty
9
10-Dimethyl-1
2-benzanthracene
Adenocarcinoma
03 medical and health sciences
Model Organisms
Folic Acid
Bcl-2-associated X protein
Breast cancer
Internal medicine
Breast Cancer
medicine
Animals
Humans
Biology
Nutrition
030304 developmental biology
lcsh:R
Cancers and Neoplasms
Mammary Neoplasms
Experimental
Cancer
medicine.disease
Rats
Endocrinology
Apoptosis
Dietary Supplements
biology.protein
Rat
lcsh:Q
Carcinogenesis
Zdroj: PLoS ONE, Vol 9, Iss 1, p e84635 (2014)
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0084635
Popis: Folic acid supplementation may prevent the development of cancer in normal tissues but may promote the progression of established (pre)neoplastic lesions. However, whether or not folic acid supplementation can promote the progression of established (pre)neoplastic mammary lesions is unknown. This is a critically important issue because breast cancer patients and survivors in North America are likely exposed to high levels of folic acid owing to folic acid fortification and widespread supplemental use after cancer diagnosis. We investigated whether folic acid supplementation can promote the progression of established mammary tumors. Female Sprague-Dawley rats were placed on a control diet and mammary tumors were initiated with 7,12-dimethylbenza[a]anthracene at puberty. When the sentinel tumor reached a predefined size, rats were randomized to receive a diet containing the control, 2.5x, 4x, or 5x supplemental levels of folic acid for up to 12 weeks. The sentinel mammary tumor growth was monitored weekly. At necropsy, the sentinel and all other mammary tumors were analyzed histologically. The effect of folic acid supplementation on the expression of proteins involved in proliferation, apoptosis, and mammary tumorigenesis was determined in representative sentinel adenocarcinomas. Although no clear dose-response relationship was observed, folic acid supplementation significantly promoted the progression of the sentinel mammary tumors and was associated with significantly higher sentinel mammary tumor weight and volume compared with the control diet. Furthermore, folic acid supplementation was associated with significantly higher weight and volume of all mammary tumors. The most significant and consistent mammary tumor-promoting effect was observed with the 2.5x supplemental level of folic acid. Folic acid supplementation was also associated with an increased expression of BAX, PARP, and HER2. Our data suggest that folic acid supplementation may promote the progression of established mammary tumors. The potential tumor-promoting effect of folic acid supplementation in breast cancer patients and survivors needs further clarification.
Databáze: OpenAIRE
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