OMEGA 3 e Carcinoma Mammario
ABSTRACTS
tratti da
PubMed, a service of the National Library of Medicine, provides access to over 12 million MEDLINE citations back to the mid-1960's and additional life science journals. PubMed includes links to many sites providing full text articles and other related resources.
Int J Cancer 2002 Mar 1;98(1):78-83
N-3 and N-6 fatty acids in
breast adipose tissue and relative risk of breast cancer in a case-control study
in Tours, France.
Maillard V, Bougnoux P, Ferrari P, Jourdan ML, Pinault M, Lavillonniere F,
Body G, Le Floch O, Chajes V.
Laboratoire de Biologie des Tumeurs, Clinique d'Oncologie-Radiotherapie, Service
de Gynecologie-Obstetrique, E.A. 2103, Unite de Recherche Associee
Universite-INRA, CHU, Tours, France.
Experimental studies have indicated that n-3 fatty acids, including
alpha-linolenic acid (18:3 n-3) and long-chain n-3 polyunsaturated fatty acids
inhibit mammary tumor growth and metastasis. Earlier epidemiological studies
have given inconclusive results about a potential protective effect of dietary
n-3 polyunsaturated fatty acids on breast cancer risk, possibly because of
methodological issues inherent to nutritional epidemiology. To evaluate the
hypothesis that n-3 fatty acids protect against breast cancer, we examined the
fatty acid composition in adipose tissue from 241 patients with invasive,
nonmetastatic breast carcinoma and from 88 patients with benign breast disease,
in a case-control study in Tours, central France. Fatty acid composition in
breast adipose tissue was used as a qualitative biomarker of past dietary intake
of fatty acids. Biopsies of adipose tissue were obtained at the time of surgery.
Individual fatty acids were measured as a percentage of total fatty acids, using
capillary gas chromatography. Unconditional logistic regression modeling was
used to obtain odds ratio estimates while adjusting for age, height, menopausal
status and body mass index. We found inverse associations between breast
cancer-risk and n-3 fatty acid levels in breast adipose tissue. Women in the
highest tertile of alpha-linolenic acid (18:3 n-3) had an odds ratio of 0.39
(95% confidence intervals [CI] = 0.19-0.78) compared to women in the lowest
tertile (trend p = 0.01). In a similar way, women in the highest tertile of
docosahexaenoic acid (22:6 n-3) had an odds ratio of 0.31 (95% CI = 0.13-0.75)
compared to women in the lowest tertile (trend p = 0.016). Women in the highest
tertile of the long-chain n-3/total n-6 ratio had an odds ratio of 0.33 (95%
confidence interval = 0.17-0.66) compared to women in the lowest tertile (trend
p = 0.0002). In conclusion, our data based on fatty acids levels in breast
adipose tissue suggest a protective effect of n-3 fatty acids on breast cancer
risk and support the hypothesis that the balance between n-3 and n-6 fatty acids
plays a role in breast cancer. Copyright 2001 Wiley-Liss, Inc.
Eur J Cancer 2001 Feb;37(3):402-13
Effects
of gamma-linolenic acid and oleic acid on paclitaxel cytotoxicity in human
breast cancer cells.
Menendez JA, del Mar Barbacid M,
Montero S, Sevilla E, Escrich E, Solanas M, Cortes-Funes H, Colomer R.
Division of Medical Oncology, Hospital Universitario 12 de Octubre, Avda.
de Cordoba Km 5.4, E-28041 Madrid, Spain.
It has been suggested that dietary interventions may improve the effectiveness
of cancer chemotherapy. We have examined the combined in vitro cytotoxicity of
paclitaxel and the fatty acids gamma-linolenic acid (GLA, 18:3n-6) and oleic
acid (OA, 18:1n-9) in human breast carcinoma MDA-MB-231 cells. The effect of
fatty acids on paclitaxel chemosensitivity was determined by comparing IC(50)
and IC(70) (50 and 70% inhibitory concentrations, respectively) obtained when
the cells were exposed to IC(50) and IC(70) levels of paclitaxel alone and fatty
acids were supplemented either before or during the exposure to paclitaxel. The
3-4,5-dimethylthiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT) assay was used
to determine cell growth inhibition. GLA by itself showed antiproliferative
effects, and a possible GLA-paclitaxel interaction at the cellular level was
assessed by the isobologram and the combination-index (CI) methods. Isobole
analysis at the isoeffect levels of 50 and 70% revealed that drug interaction
was predominantly synergistic when GLA and paclitaxel were added concurrently
for 24 h to the cell cultures. Interaction assessment using the median-effect
principle and the combination-index (CI) method showed that exposure of
MDA-MB-231 cells to an equimolar combination of concurrent GLA plus paclitaxel
for 24 h resulted in a moderate synergism at all effect levels, consistent with
the results of the isobologram analysis. When exposure to GLA (24 h) was
followed sequentially by paclitaxel (24 h) only an additive effect was observed.
The GLA-mediated increase in paclitaxel chemosensitivity was only partially
abolished by Vitamin E, a lipid peroxidation inhibitor, suggesting a limited
influence of the oxidative status of GLA in achieving potentiation of paclitaxel
toxicity. When OA (a non-peroxidisable fatty acid) was combined with paclitaxel,
an enhancement of chemosensitivity was found when OA was used concurrently with
paclitaxel, although less markedly than with GLA. Pretreatment of MDA-MB-231
cells with OA for 24 h prior to a 24 h paclitaxel exposure produced greater
enhancement of paclitaxel sensitivity at high OA concentrations than the
concurrent exposure to OA and paclitaxel. The OA-induced sensitisation to
paclitaxel was not due to the cytoxicity of the fatty acid itself. When these
observations were extended to three additional breast carcinoma cell lines
(SK-Br3, T47D and MCF-7), simultaneous exposure to GLA and paclitaxel also
resulted in synergism. GLA preincubation followed by paclitaxel resulted in
additivity for all cell lines. Simultaneous exposure to paclitaxel and OA
enhanced paclitaxel cytotoxicity in T47D and MCF-7 cells, but not in SK-Br3
cells, whereas preincubation with OA failed to increase paclitaxel effectiveness
in all three cell lines. For comparison, the effects of other fatty acids on
paclitaxel chemosensitivity were examined: GLA was the most potent at
enhancing paclitaxel cytotoxicity, followed by alpha-linolenic acid (ALA;
18:3n.3), eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA;
22:6n-3), whereas linoleic acid (LA; 18:2n-6) did not increase paclitaxel
toxicity. These findings provide experimental support for the use of fatty
acids as modulators of tumour cell chemosensitivity in paclitaxel-based therapy.
Breast Cancer Res Treat 2000 Dec;64(3):287-96
Effect
of melatonin and linolenic acid on mammary cancer in transgenic mice with c-neu
breast cancer oncogene.
Rao GN, Ney E, Herbert RA.
Environmental Toxicology Program, National Institute of Environmental Health
Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
rao@niehs.nih.gov
Breast cancer is one of the most common cancers and is a leading cause of
mortality in women. The TG.NK transgenic mouse line expresses the c-neu breast
cancer oncogene under the control of a MMTV promoter and appears to be a useful
animal model for evaluation of intervention strategies to delay/prevent breast
cancer.
Fiber-rich nonpurified diet (NTP-2000) and some retinoid analogues have been shown to significantly delay the development of mammary cancer in the TG.NK model.
Four-week-old hemizygous TG.NK female mice with MMTV/c-neu oncogene fed NTP-2000 diet were gavaged with 0.05-0.2 ml of flaxseed oil as the source of omega-3 rich PUFA, or melatonin at 50-200 mg/kg or a combination of 0.10 ml flaxseed oil and 50 mg/kg melatonin in a gavage volume of 0.2 ml per mouse with corn oil as the vehicle for 30 weeks.
The time course of the mammary tumor incidence pattern was advanced by flaxseed oil compared to the control.
At the high dose (0.2 ml) of flaxseed oil, when the
omega-6: omega-3 PUFA ratio was closer to 1, there was some delay in the growth
of mammary tumors.
Melatonin delayed the appearance of palpable tumors and the growth of the tumors with a dose-related statistically significant negative trend for the incidence of tumors.
The combination of flaxseed oil and melatonin caused a significant decrease in the number of tumors and tumor weight per mouse compared to the control and to flaxseed oil but not to melatonin alone.
Flaxseed oil may delay the growth of mammary tumors if the omega-6:omega-3 PUFA ratio of fat consumed is closer to 1.
Melatonin has the potential to markedly delay the appearance of palpable mammary tumors.
Studies are in progress with the TG.NK mouse model to understand the histological and molecular changes associated with the dose-response pattern of mammary tumor incidence and growth after treatment with a broad range of doses of melatonin.
Eur J Cancer 2000 Feb;36(3):335-40
Low alpha-linolenic acid
content of adipose breast tissue is associated with an increased risk of breast
cancer.
Klein V, Chajes V, Germain E, Schulgen G, Pinault M, Malvy D, Lefrancq T,
Fignon A, Le Floch O, Lhuillery C, Bougnoux P.
Laboratoire de Biologie des
Tumeurs, d'anatomo-pathologie, Clinique d'Oncologie-Radiotherapie, Service de
Gynecologie-Obstetrique, E. A. 2103, Unite de Recherche Associee
Universite-INRA, CHU, Tours, France.
Data derived from experimental studies suggest that alpha-linolenic acid
may have a protective effect in breast cancer. Observations obtained from
epidemiological studies have not allowed conclusions to be drawn about a
potential protective effect of dietary alpha-linolenic acid on breast cancer,
possibly because of methodological issues. This case-control study conducted in
an homogeneous population from a central area in France was designed to explore
the hypothesis that alpha-linolenic acid inhibits breast cancer, using fatty
acid levels in adipose breast tissue as a biomarker of past qualitative dietary
intake of fatty acids. Biopsies of adipose breast tissue at the time of
diagnosis were obtained from 123 women with invasive non-metastatic breast
carcinoma. 59 women with benign breast disease served as controls. Individual
fatty acids were analysed by capillary gas chromatography. An unconditional
logistic regression model was used to obtain odds ratio estimates whilst
adjusting for age, menopausal status and body mass index (BMI). No association
was found between fatty acids (saturates, monounsaturates, long-chain
polyunsaturates n-6 or n-3) and the disease, except for alpha-linolenic acid
which showed an inverse association with the risk of breast cancer. The relative
risk of breast cancer for women in the highest quartile of adipose breast tissue
alpha-linolenic acid level was 0.36 (95% confidence interval=0.12-1.02) compared
with those in the lowest quartile (P trend=0.026), suggesting a protective
effect of alpha-linolenic acid in the risk of breast cancer. The effects of
dietary alpha-linolenic on the risk of breast cancer warrant further study.
Nutr Cancer 2000;36(1):33-41
Effect
of an alpha-linolenic acid-rich diet on rat mammary tumor growth depends on the
dietary oxidative status.
Cognault S, Jourdan ML, Germain E, Pitavy R, Morel E, Durand G, Bougnoux P,
Lhuillery C.
Laboratoire de Nutrition et Securite Alimentaire, Institut National de la
Recherche Agronomique, Jouy-en-Josas, France.
To investigate whether the oxidative status of an 18:3(n-3) polyunsaturated
fatty acid (PUFA)-enriched diet could modulate the growth of chemically induced
rat mammary tumors, three independent experiments were performed. Experiments I
and II examined the variation of tumor growth by addition of antioxidant (vitamin E) or a prooxidant system
(sodium ascorbate/2-methyl-1,4-naphthoquinone) to a 15% linseed oil diet rich in
18:3(n-3). Experiment III addressed the role of PUFA in the tumor growth
modulation by vitamin E. For this purpose, we compared the effect of vitamin E
in 15% fat diets containing a high level of 18:3(n-3) (linseed oil, high-PUFA
diet) or devoid of 18:3(n-3) (hydrogenated palm/sunflower oil, low-PUFA diet).
In Experiments I-III, tumor growth increased in the presence of vitamin E
compared with control (without vitamin E). Furthermore, it decreased when
prooxidant was added. In contrast, no difference was observed when the diet was
low in PUFA, suggesting that sensitivity of PUFA to peroxidation may interfere
with tumor growth. This observation was supported by growth kinetic parameter
analysis, which indicated that tumor growth resulted from variations in cell
loss but not from changes in cell proliferation. These data show that, in vivo,
PUFA effects on tumor growth are highly dependent on diet oxidative status.