Skip to main content
Erschienen in: European Journal of Nutrition 2/2017

18.11.2015 | Original Contribution

Increased dietary levels of α-linoleic acid inhibit mammary tumor growth and metastasis

verfasst von: Marianela Vara-Messler, Maria E. Pasqualini, Andrea Comba, Renata Silva, Carola Buccellati, Annalisa Trenti, Lucia Trevisi, Aldo R. Eynard, Angelo Sala, Chiara Bolego, Mirta A. Valentich

Erschienen in: European Journal of Nutrition | Ausgabe 2/2017

Einloggen, um Zugang zu erhalten

Abstract

Objective

The aim of this study was to determine whether α-linolenic acid (ALA ω-3 fatty acid) enriched diet affects growth parameters when applied to a syngeneic model of mammary carcinoma.

Materials and methods

BALB/c mice were divided and fed with: 1) a chia oil diet, rich in ALA or 2) a corn oil diet, rich in linoleic acid (LA ω-6 fatty acid). Mice were subcutaneously inoculated with a tumor cell line LM3, derived from a murine mammary adenocarcinoma.

Results

After 35 days, tumor incidence, weight, volume and metastasis number were lower in the ALA-fed mice, while tumor latency time was higher, and the release of pro-tumor metabolites derived from ω-6 fatty acids decreased in the tumor. Compared to the control group, a lower number of mitosis, a higher number of apoptotic bodies and higher T-lymphocyte infiltration were consistently observed in the ALA group. An ALA-rich diet decreased the estrogen receptor (ER) α expression, a recognized breast cancer promotor while showing an opposite effect on ERβ in tumor lysates.

Conclusion

These data support the anticancer effect of an ALA-enriched diet, which might be used as a dietary strategy in breast cancer prevention.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Ronco AL, De Stéfani E, Stoll M (2010) Hormonal and metabolic modulation through nutrition: towards a primary prevention of breast cancer. Breast 19(5):322–332CrossRef Ronco AL, De Stéfani E, Stoll M (2010) Hormonal and metabolic modulation through nutrition: towards a primary prevention of breast cancer. Breast 19(5):322–332CrossRef
2.
Zurück zum Zitat Lelièvre SA, Weaver CM (2013) Global nutrition research: nutrition and breast cancer prevention as a model. Nutr Rev 71(11):742–752CrossRef Lelièvre SA, Weaver CM (2013) Global nutrition research: nutrition and breast cancer prevention as a model. Nutr Rev 71(11):742–752CrossRef
3.
Zurück zum Zitat Eynard AR (2003) Potential of essential fatty acids as natural therapeutic products for human tumors. Nutrition 19(4):386–388CrossRef Eynard AR (2003) Potential of essential fatty acids as natural therapeutic products for human tumors. Nutrition 19(4):386–388CrossRef
4.
Zurück zum Zitat Serhan CN (2014) Pro-resolving lipid mediators are leads for resolution physiology. Nature 510(7503):92–101CrossRef Serhan CN (2014) Pro-resolving lipid mediators are leads for resolution physiology. Nature 510(7503):92–101CrossRef
5.
Zurück zum Zitat Subedi K, Yu HM, Newell M, Weselake RJ, Meesapyodsuk D et al (2015) Stearidonic acid-enriched flax oil reduces the growth of human breast cancer in vitro and in vivo. Breast Cancer Res Treat 149(1):17–29CrossRef Subedi K, Yu HM, Newell M, Weselake RJ, Meesapyodsuk D et al (2015) Stearidonic acid-enriched flax oil reduces the growth of human breast cancer in vitro and in vivo. Breast Cancer Res Treat 149(1):17–29CrossRef
6.
Zurück zum Zitat Cho K, Mabasa L, Fowler AW, Walsh DM, Park CS (2010) Canola oil inhibits breast cancer cell growth in cultures and in vivo and acts synergistically with chemotherapeutic drugs. Lipids 45(9):777–784CrossRef Cho K, Mabasa L, Fowler AW, Walsh DM, Park CS (2010) Canola oil inhibits breast cancer cell growth in cultures and in vivo and acts synergistically with chemotherapeutic drugs. Lipids 45(9):777–784CrossRef
7.
Zurück zum Zitat Muñoz SE, Silva RA, Lamarque A, Guzman CA, Eynard AR (1995) Protective capability of dietary Zizyphus mistol L. seed oil, rich in 18:3 n-3, on the development of two murine mammary gland adenocarcinomas with high or low metastatic potential. Prostagl Leuk Essent Fat Acids 53:135–138CrossRef Muñoz SE, Silva RA, Lamarque A, Guzman CA, Eynard AR (1995) Protective capability of dietary Zizyphus mistol L. seed oil, rich in 18:3 n-3, on the development of two murine mammary gland adenocarcinomas with high or low metastatic potential. Prostagl Leuk Essent Fat Acids 53:135–138CrossRef
8.
Zurück zum Zitat Banno N, Akihisa T, Tokuda H, Yasukawa K, Higashihara H et al (2004) Triterpene acids from the leaves of Perilla frutescens and their anti-inflammatory and antitumor-promoting effects. Biosci Biotechnol Biochem 68(1):85–90CrossRef Banno N, Akihisa T, Tokuda H, Yasukawa K, Higashihara H et al (2004) Triterpene acids from the leaves of Perilla frutescens and their anti-inflammatory and antitumor-promoting effects. Biosci Biotechnol Biochem 68(1):85–90CrossRef
9.
Zurück zum Zitat Espada CE, Berra MA, Martinez MJ, Eynard AR, Pasqualini ME (2007) Effect of chia oil (Salvia hispanica) rich in w-3 fatty acids on the eicosanoid release, apoptosis and T-lymphocyte tumor infiltration in a murine mammary gland adenocarcinoma. Prostagl Leuk Essent Fat Acids 77:21–28CrossRef Espada CE, Berra MA, Martinez MJ, Eynard AR, Pasqualini ME (2007) Effect of chia oil (Salvia hispanica) rich in w-3 fatty acids on the eicosanoid release, apoptosis and T-lymphocyte tumor infiltration in a murine mammary gland adenocarcinoma. Prostagl Leuk Essent Fat Acids 77:21–28CrossRef
10.
Zurück zum Zitat Gleissman H, Johnsen JI, Kogner P (2010) Omega-3 fatty acids in cancer, the protectors of good and the killers of evil? Exp Cell Res 316(8):1365–1373CrossRef Gleissman H, Johnsen JI, Kogner P (2010) Omega-3 fatty acids in cancer, the protectors of good and the killers of evil? Exp Cell Res 316(8):1365–1373CrossRef
11.
Zurück zum Zitat Lu IF, Hasio AC, Hu MC, Yang FM, Su HM (2010) Docosahexaenoic acid induces proteasome-dependent degradation of estrogen receptor alpha and inhibits the downstream signaling target in MCF-7 breast cancer cells. J Nutr Biochem 21(6):512–517CrossRef Lu IF, Hasio AC, Hu MC, Yang FM, Su HM (2010) Docosahexaenoic acid induces proteasome-dependent degradation of estrogen receptor alpha and inhibits the downstream signaling target in MCF-7 breast cancer cells. J Nutr Biochem 21(6):512–517CrossRef
12.
Zurück zum Zitat Fox EM, Davis RJ, Shupnik MA (2008) ERβ in breast cancer—onlooker, passive player, or active protector? Steroids 73(11):1039–1051CrossRef Fox EM, Davis RJ, Shupnik MA (2008) ERβ in breast cancer—onlooker, passive player, or active protector? Steroids 73(11):1039–1051CrossRef
13.
Zurück zum Zitat Herynk MH, Fuqua SA (2004) Estrogen receptor mutations in human disease. Endocr Rev 25:869–898CrossRef Herynk MH, Fuqua SA (2004) Estrogen receptor mutations in human disease. Endocr Rev 25:869–898CrossRef
14.
Zurück zum Zitat Puricelli L, Colombo LL, Bal de Kier Joffé E, de Lustig ES (1984) Invasiveness in vitro of two mammary adenocarcinoma tumors with different metastasizing ability. Invasio Metast 4:238–246 Puricelli L, Colombo LL, Bal de Kier Joffé E, de Lustig ES (1984) Invasiveness in vitro of two mammary adenocarcinoma tumors with different metastasizing ability. Invasio Metast 4:238–246
15.
Zurück zum Zitat Folch J (1957) A simple method for the isolation and purification of total lipids from animal tissue. J Biol Chem 226:497–509 Folch J (1957) A simple method for the isolation and purification of total lipids from animal tissue. J Biol Chem 226:497–509
16.
Zurück zum Zitat Pasqualini ME, Berra MA, Calderón RO, Cremonezzi D, Giraudo C et al (2005) Dietary lipids modulate eicosanoid release and apoptosis of cells of a murine lung alveolar carcinoma. Prostagl Leuk Essent Fat Acids 72:235–240CrossRef Pasqualini ME, Berra MA, Calderón RO, Cremonezzi D, Giraudo C et al (2005) Dietary lipids modulate eicosanoid release and apoptosis of cells of a murine lung alveolar carcinoma. Prostagl Leuk Essent Fat Acids 72:235–240CrossRef
17.
Zurück zum Zitat Lowry OH, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275 Lowry OH, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275
18.
Zurück zum Zitat Toniolo A, Warden EA, Nassi A, Cignarella A, Bolego C (2013) Regulation of SIRT1 in vascular smooth muscle cells from streptozotocin-diabetic rats. PLoS One. 8(5):e65666 Toniolo A, Warden EA, Nassi A, Cignarella A, Bolego C (2013) Regulation of SIRT1 in vascular smooth muscle cells from streptozotocin-diabetic rats. PLoS One. 8(5):e65666
19.
Zurück zum Zitat Hosek J, Toniolo A, Neuwirth O, Bolego C (2013) Prenylated and geranylated flavonoids increase production of reactive oxygen species in mouse macrophages but inhibit the inflammatory response. J Nat Prod 76(9):1586–1591CrossRef Hosek J, Toniolo A, Neuwirth O, Bolego C (2013) Prenylated and geranylated flavonoids increase production of reactive oxygen species in mouse macrophages but inhibit the inflammatory response. J Nat Prod 76(9):1586–1591CrossRef
20.
Zurück zum Zitat American Oil Chemists’ Society (1998) Official methods and recommended practices of the AOCS. American Oil Chemists’ Society, Champaign American Oil Chemists’ Society (1998) Official methods and recommended practices of the AOCS. American Oil Chemists’ Society, Champaign
21.
Zurück zum Zitat Rathore AS, Kumar S, Konwar R, Makker A, Negi MP et al (2014) CD3+, CD4+ and CD8+ tumour infiltrating lymphocytes (TILs) are predictors of favourable survival outcome in infiltrating ductal carcinoma of breast. Indian J Med Res 140(3):361–369 Rathore AS, Kumar S, Konwar R, Makker A, Negi MP et al (2014) CD3+, CD4+ and CD8+ tumour infiltrating lymphocytes (TILs) are predictors of favourable survival outcome in infiltrating ductal carcinoma of breast. Indian J Med Res 140(3):361–369
22.
Zurück zum Zitat Liu S, Edgerton SM, Moore DH 2nd, Thor AD (2001) Measures of cell turnover (proliferation and apoptosis) and their association with survival in breast cancer. Clin Cancer Res 7(6):1716–1723 Liu S, Edgerton SM, Moore DH 2nd, Thor AD (2001) Measures of cell turnover (proliferation and apoptosis) and their association with survival in breast cancer. Clin Cancer Res 7(6):1716–1723
23.
Zurück zum Zitat Corsetto PA, Montorfano G, Zava S, Jovenitti IE, Cremona A et al (2011) Effects of n-3 PUFAs on breast cancer cells through their incorporation in plasma membrane. Lipids Health Dis 12(10):73CrossRef Corsetto PA, Montorfano G, Zava S, Jovenitti IE, Cremona A et al (2011) Effects of n-3 PUFAs on breast cancer cells through their incorporation in plasma membrane. Lipids Health Dis 12(10):73CrossRef
24.
Zurück zum Zitat Larsson SC, Kumlin M, Ingelman-Sundberg M, Wolk A (2004) Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms. Am J Clin Nutr 79:935–945 Larsson SC, Kumlin M, Ingelman-Sundberg M, Wolk A (2004) Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms. Am J Clin Nutr 79:935–945
25.
Zurück zum Zitat Corsetto PA, Cremona A, Montorfano G, Jovenitti IE, Orsini F et al (2012) Chemical-physical changes in cell membrane microdomains of breast cancer cells after omega-3 PUFA incorporation. Cell Biochem Biophys 64:45–59CrossRef Corsetto PA, Cremona A, Montorfano G, Jovenitti IE, Orsini F et al (2012) Chemical-physical changes in cell membrane microdomains of breast cancer cells after omega-3 PUFA incorporation. Cell Biochem Biophys 64:45–59CrossRef
26.
Zurück zum Zitat Williams JA, Batten SE, Harris M, Rockett BD, Shaikh SR et al (2012) Docosahexaenoic and eicosapentaenoic acids segregate differently between raft and nonraft domains. Biophys J 103:228–237CrossRef Williams JA, Batten SE, Harris M, Rockett BD, Shaikh SR et al (2012) Docosahexaenoic and eicosapentaenoic acids segregate differently between raft and nonraft domains. Biophys J 103:228–237CrossRef
27.
Zurück zum Zitat Wallace JM (2002) Nutritional and botanical modulation of the inflammatory cascade-eicosanoids, cyclooxygenases, and lipoxygenases-as an adjunct in cancer therapy. Integr Cancer Ther 1:7–37 Wallace JM (2002) Nutritional and botanical modulation of the inflammatory cascade-eicosanoids, cyclooxygenases, and lipoxygenases-as an adjunct in cancer therapy. Integr Cancer Ther 1:7–37
28.
Zurück zum Zitat Cabral M, Martín-Venegas R, Moreno JJ (2013) Role of arachidonic acid metabolites on the control of non-differentiated intestinal epithelial cell growth. Int J Biochem Cell Biol 45:1620–1628CrossRef Cabral M, Martín-Venegas R, Moreno JJ (2013) Role of arachidonic acid metabolites on the control of non-differentiated intestinal epithelial cell growth. Int J Biochem Cell Biol 45:1620–1628CrossRef
29.
Zurück zum Zitat Hsi LC, Wilson L, Nixon J, Eling TE (2001) 15-lipoxygenase-1 metabolites down-regulate peroxisome proliferator-activated receptor gamma via the MAPK signaling pathway. J Biol Chem 276(37):34545–34552CrossRef Hsi LC, Wilson L, Nixon J, Eling TE (2001) 15-lipoxygenase-1 metabolites down-regulate peroxisome proliferator-activated receptor gamma via the MAPK signaling pathway. J Biol Chem 276(37):34545–34552CrossRef
30.
Zurück zum Zitat Zhang G, Panigrahy D, Mahakian LM, Yang J, Liu JY et al (2013) Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis. Proc Natl Acad Sci USA 110(16):6530–6535CrossRef Zhang G, Panigrahy D, Mahakian LM, Yang J, Liu JY et al (2013) Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis. Proc Natl Acad Sci USA 110(16):6530–6535CrossRef
31.
Zurück zum Zitat Serhan CN (2011) The resolution of inflammation: the devil in the flask and in the details. FASEB J 25:1441–1448CrossRef Serhan CN (2011) The resolution of inflammation: the devil in the flask and in the details. FASEB J 25:1441–1448CrossRef
32.
Zurück zum Zitat Coronella JA, Spier C, Welch M, Trevor KT, Stopeck AT et al (2002) Antigen-driven oligoclonal expansion of tumor-infiltrating B cells in infiltrating ductal carcinoma of the breast. J Immunol 169:1829–1836CrossRef Coronella JA, Spier C, Welch M, Trevor KT, Stopeck AT et al (2002) Antigen-driven oligoclonal expansion of tumor-infiltrating B cells in infiltrating ductal carcinoma of the breast. J Immunol 169:1829–1836CrossRef
33.
Zurück zum Zitat Toso JF, Oei C, Oshidari F, Tartaglia J, Paoletti E et al (1996) MAGE-1-specific precursor cytotoxic T-lymphocytes present among tumor-infiltrating lymphocytes from a patient with breast cancer: characterization and antigen-specific activation. Cancer Res 56:16–20 Toso JF, Oei C, Oshidari F, Tartaglia J, Paoletti E et al (1996) MAGE-1-specific precursor cytotoxic T-lymphocytes present among tumor-infiltrating lymphocytes from a patient with breast cancer: characterization and antigen-specific activation. Cancer Res 56:16–20
34.
Zurück zum Zitat Rabinowich H, Cohen R, Bruderman I, Steiner Z, Klajman A (1987) A functional analysis of mononuclear cell infiltrating into tumors: lysis of autologous human tumor cells by cultured infiltrating lymphocytes. Cancer Res 47:173–177 Rabinowich H, Cohen R, Bruderman I, Steiner Z, Klajman A (1987) A functional analysis of mononuclear cell infiltrating into tumors: lysis of autologous human tumor cells by cultured infiltrating lymphocytes. Cancer Res 47:173–177
35.
Zurück zum Zitat Yuan B, Cheng L, Chiang HC, Xu X, Han Y, Su H, Wang L et al (2014) A phosphotyrosine switch determines the antitumor activity of ERβ. J Clin Invest 124(8):3378–3390CrossRef Yuan B, Cheng L, Chiang HC, Xu X, Han Y, Su H, Wang L et al (2014) A phosphotyrosine switch determines the antitumor activity of ERβ. J Clin Invest 124(8):3378–3390CrossRef
Metadaten
Titel
Increased dietary levels of α-linoleic acid inhibit mammary tumor growth and metastasis
verfasst von
Marianela Vara-Messler
Maria E. Pasqualini
Andrea Comba
Renata Silva
Carola Buccellati
Annalisa Trenti
Lucia Trevisi
Aldo R. Eynard
Angelo Sala
Chiara Bolego
Mirta A. Valentich
Publikationsdatum
18.11.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nutrition / Ausgabe 2/2017
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-015-1096-6

Weitere Artikel der Ausgabe 2/2017

European Journal of Nutrition 2/2017 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.