|
ISTITUTO DI MEDICINA BIOLOGICA
dr G. Di Fede
PUFA
biomarkers in assessment of cancer patients.
A proposal
B. Berra, G. Montorfano, A.M. Rizzo
Institute of General Physiology and Biochemistry "G.
Esposito"
University of Milano Via D. Trentacoste, 2 - 20134
Milano Italy
INTRODUCTION
Omega 3 are important molecules for membrane order; they can also
modify gene-expression, content of inflammation-inducible cytokines,
regulation of eicosanoid production, plasma triglycerides level, blood
pressure, and ion flux in cardiac cells. So there have been successful
trials with eicosapentaenoic acid (C20:5 ω-3, EPA) and
docosaexahaenoic acid (C22:6 ω-3, DHA) of secondary prevention of
myocardial infarction, fatal arrhytmias and coronary hearth disease.
These observations show they play an important role in the
cardiovascoular system.
The effects of ω -3 in patients with cardiovascular diseases (CVD)
were the driving force for the valuation of PUFA-based biomarker for
the assessment of coronary heart diseases, which could serve as
measures of the risk for developing CVD and SCD.
Colorectal cancer
Omega-3 have been hypothesized to influence colorectal carcinogenesis
through many mechanisms (e.g. inhibiting COX2, increasing apoptosis,
reducing angiogenesis). Low dose of DHA synergistically interacts with
araC, suggesting that dietary supplementation of DHA might achieve
therapeutic gain.
Breast cancer
Supplementation with DHA synergistically enhances toxane cytotoxicity,
down regulate HER-2/neu (c-erb B-2) oncogene expression, modifies the
production of the heparansulfate syndecan-1, suggesting a
gene-nutrient interaction of critical importance for mammary
carcinogenesis and supporting the hypothesis that ω-3 can be used as
modulators of tumor cell chemiosensitivity.
AIM OF
THE STUDY
We would like to evaluate the potential value of tumor risk assessment
in colon and breast cancer patients by determining ω-3 concentration
in blood in healthy subjects, cancer free patients and patients with
colon or breast cancer, before and after supplementation with (ω-3,
evaluating the potential correlation with the clinical conditions.
MATERIALS AND METHODS
Arachidonic acid (AA) and eicosapentaenoic acid (EPA) content in blood
were determined by gaschromatographic analysis. The methylesters fatty
acids were obtained with sodium methoxide in methanol 3.33% w/v and
injected into an Agilent gaschromatograph (HP 6850, series II plus),
equipped with FID detector under the following experimental conditions:
Capillary column: AT Silar ALLTECH (50% cyanopropyl - 50% methyl
polysiloxane) length 30 m, i.d. 0.32 mm, film thickness 0.25 μm. Gas
carrier: helium, flow rate 2.7 ml/min. Temperature: injector 250°C,
detector 275°C, oven 50°C for 2 minutes, rate of 10°C/minute until
200°C for 20 minutes. Standard: a standard mixture containing
arachidonic acid and eicosapentaenoic acid was injected to identify
sample peaks. The procedure was validated according the more recent
rules (ISO 9001:2000).
The AA/EPA ratio was calculated on blood samples from 600 healthy
subjects and 46 pathological subjects.
RESULTS AND DISCUSSION
We analyzed 295 healthy subjects, on a normal diet and 268 after
omega-3 supplementation. The ratio AA/EPA was 15.25±10.36 and
4.07±3.44 respectively in the 1st and 2nd group. We have also analyzed
38 and 6 patients respectively with breast and colon cancer. The ratio
AA/EPA was 18.20±9.36 in patients with tumors without supplementation
and 4.07±3.44 in patients after supplementation. In 150 subjects the
AA/EPA ratio in blood correlate with the AA/EPA ratio in cell membrane
phospholipids of erythrocytes (RBC).
CONCLUSIONS
Conclusion 1: the correlation between plasma and RBC
phospholipids we found suggests that the easier analysis in blood
samples is a good tool for the evaluation of the ratio AA/EPA.
Conclusion 2: in colon and breast cancer patients the
concentration of omega-3 LCPUFA is lower in comparison with normal
subjects.
Conclusion 3: the supplement with omega-3 results in
restablishing normal value of the ratio ω3 / ω6.
Conclusion 4: the preliminary results in colon and breast
cancer patients obtained seems to indicate that the ratio AA/EPA.
could be included as a new biomarker in the follow-up of patients
under traditional chemotherapy supplemented, according to the recent
data of literature with PUFA omega-3 fatty acids (Wu M. et al. Omega-3
polyunsaturated fatty acids attenuate breast cancer growth through
activation of a neutral sphingomyelinase-mediated pathway. Int. J.
Cancer, 117, 340-348 2005; Astorg P., Dietary fatty acids and
colorectal and prostate cancers: epidemiological studies. Bull Cancer.
2005 Jul;92(7):670-84).
|