Lycopene studies

Characteristics of Prostate Cell Lines Used in Lycopene Studies.440... 

CHARACTERISTICS OF PROSTATE CELL LINES USED IN LYCOPENE STUDIES... 

An evaluation of the Health Professionals Follow-Up Study (Giovannucci et al., 1995) has detected a lower prostate cancer risk associated with the greater consumption of tomatoes and related food products. Tomatoes are the primary dietary source of lycopene and lycopene concentrations are highest in testis and adrenal tissue (Clinton, 1998). In paired benign and malignant prostate tissue from 25 American men, 53-74 yrs, undergoing... 

The relationship between serum and tissue concentrations of lutein and zeaxanthin was recently studied by Johnson et al, (2000). Dietary intake of xanthophyll-rich vegetables (for example, spinach and com) resulted in significant increases in lutein concentration in serum, adipose tissue and buccal cells, and this correlated with changes in MP density. However, P-carotene and lycopene are normally the major carotenoids detected in buccal cells (Peng et al, 1994). 

Carotenoid accumulation during fruit ripening in tomato has been studied extensively and is a good model system to elucidate the regulation of the process. During ripening the concentration of carotenoids increases between 10 and 15-fold due mainly to a 500-fold increase in the concentration of lycopene (Fraser et al, 1994 Table 13.5). Accumulation of lycopene begins... 

The carotenoid pathway may also be regulated by feedback inhibition from the end products. Inhibition of lycopene cyclisation in leaves of tomato causes increase in the expression of Pds and Psy-1 (Giuliano et al, 1993 Corona et al, 1996). This hypothesis is supported by other studies using carotenoid biosynthesis inhibitors where treated photosynthetic tissues accumulated higher concentrations of carotenoids than untreated tissues (reviewed by Bramley, 1993). The mechanism of this regulation is unknown. A contrary view, however, comes from studies on the phytoene-accumulating immutans mutant of Arabidopsis, where there is no feedback inhibition of phytoene desaturase gene expression (Wetzel and Rodermel, 1998). 

GIOVANNUCCI E, RIMM E B, LIU Y, STAMPFER M J and WILLETT w c (2002) A prospective study of tomato products, lycopene and prostate cancer risk , J Natl Cancer Inst, 94, 391-8. 

Carotenoids and prostate cancer — Numerous epidemiological studies including prospective cohort and case-control studies have demonstrated the protective roles of lycopene, tomatoes, and tomato-derived products on prostate cancer risk other carotenoids showed no effects. " In two studies based on correlations between plasma levels or dietary intake of various carotenoids and prostate cancer risk, lycopene appeared inversely associated with prostate cancer but no association was reported for a-carotene, P-carotene, lutein, zeaxanthin, or p-cryptoxanthin. - Nevertheless, a protective role of all these carotenoids (provided by tomatoes, pumpkin, spinach, watermelon, and citrus fruits) against prostate cancer was recently reported by Jian et al. ... 

Supplementation study Oleoresin (equivalent to 30 mg/day Lycopene PSA and tumors - 24... 

Supplementation study Tomato sauce-based pasta Lycopene Serum and prostate levels + 25... 

Intervention trials confirmed this protective role of lycopene on prostate cancer risk. Three primary intervention studies evaluated the effect of lycopene supplementation on prostate cancer risk or on certain risk markers such as prostate-specific antigen (PSA) plasma concentration or oxidative alterations of leucocyte DNA. - All showed increases of plasma and prostate lycopene levels after diet supplementation with lycopene and inverse correlations between tumor incidence and risk biomarkers. 

Carotenoids and urino-digestive cancers — On the whole, findings from epidemiological studies did not demonstrate a protective role of carotenoids against colorectal, gastric, and bladder cancers. Indeed, most prospective and case-control studies of colorectal cancer showed no association with dietary intake or plasma level of most carotenoids. - Only lycopene and lutein were shown to be protective against colorectal cancer. Otherwise, findings from the ATBC study s showed no effect of P-carotene supplementation on colorectal cancer. 

Data concerning gastric cancer are scarce. The prospective Netherlands Cohort Study found no correlation between lutein dietary intake and gastric cancer risk, whereas findings from the Physicians Health Study and the ATBC study reported no effect of P-carotene on gastric cancer incidence. Two case-control studies and three intervention trials (ATBC, CARET, and the Physicians Health Study ) showed no association of P-carotene, lycopene, lutein, zeaxanthin, and P-cryptoxanthin. 

Among 27 prospective and case-control studies, 16 reported inverse associations between some carotenoids and CVDs, taking plasma or serum concentration as carotenoid biomarkers (11 of 16 studies), dietary intake (5 of 16 studies), or adipose tissue level (1 of 16 studies). With regard to the findings from the studies based on CVD risk, only two of seven presented significant inverse associations of carotenoids, particularly lycopene and P-carotene, whereas five studies of nine showed inverse correlations between myocardial infarcts and lycopene and/or P-carotene the others presented no associations. ... 

Some prospective and case-control studies also investigated the relationship of carotenoids and the evolution of CCA-IMT. Although the EVA study showed no association between total carotenoids and IMT, others like the ARIC study, the Los Angeles Atherosclerosis Study, " and the Kuopio Ischaemic Heart Disease Risk Factor Study demonstrated the protective role of isolated carotenoids such as lycopene, lutein, zeaxanthin, and P-cryptoxanthin on IMT. Thus, findings from prospective and case-control studies have suggested that some carotenoids such as lycopene and P-carotene may present protective effects against CVD and particularly myocardial infarcts and intima media thickness, a marker of atherosclerosis. 

However, intervention trials investigating the effects of P-carotene and lycopene supplementation on CVD have not reported convincing results (Table 3.1.3). Among the seven studies reviewed herein, four primary prevention trials, namely the Multicenter Skin Cancer Prevention Study, the Beta Carotene and Retinol Efficacy Trial, the ATBC cancer prevention study, " and the Physicians Health Study have shown no association between a supplementation of P-carotene and risk of death from CVD or fatal and non-fatal MI. 

Epidemiological data on carotenoids and cerebral infarcts or strokes indicate a protective effect of P-carotene and lycopene. Indeed, the Basel prospective study, the Kuopio Ischaemic Heart Disease Risk Factor study, and the Physicians Health Study " have shown an inverse correlation between carotenoid plasma level and risk of stroke. In the same way, Hirvonen et al. demonstrated, in findings from the ATBC cancer prevention stndy, an inverse association between P-carotene dietary intake and stroke. However, clinical data on carotenoids and stroke are nonexistent and they are needed to confirm this possible protective effect of carotenoids on stroke. 

Etminan, M. et al.. The role of tomato products and lycopene in the prevention of prostate cancer a meta-analysis of observational studies. Cancer Epidemiol. Biomarkers Prev., 13, 340, 2004. 

Rissanen, T.H. et al.. Serum lycopene concentrations and carotid atherosclerosis the Kuopio Ischaemic Heart Disease Risk Factor Study, Am. J. Clin. Nutr, 77, 133, 2003. 

Agarwal, S. and Rao, A.V., Tomato lycopene and low density lipoprotein oxidation a human dietary intervention study. Lipids, 33, 981, 1998. 

Stndies of the antoxidation of carotenoids in liposomal suspensions have also been performed since liposomes can mimic the environment of carotenoids in vivo. Kim et al. stndied the antoxidation of lycopene," P-carotene," and phytofluene" " in liposomal snspensions and identified oxidative cleavage compounds. Stabilities to oxidation at room temperature of various carotenoids incorporated in pig liver microsomes have also been studied." The model took into account membrane dynamics. After 3 hr of reactions, P-carotene and lycopene had completely degraded, whereas xanthophylls tested were shown to be more stable. 

In the second oxidation method, a metalloporphyrin was used to catalyze the carotenoid oxidation by molecular oxygen. Our focus was on the experimental modeling of the eccentric cleavage of carotenoids. We used ruthenium porphyrins as models of cytochrome P450 enzymes for the oxidation studies on lycopene and P-carotene. Ruthenium tetraphenylporphyrin catalyzed lycopene oxidation by molecular oxygen, producing (Z)-isomers, epoxides, apo-lycopenals, and apo-lycopenones. 

The underlying mechanisms involved in the activities of carotenoid oxidation products are due either to a possible role as precursors of retinoids that would be the active species for positive effects or to their own specific activities. This latter case is illustrated by the activity of non-provitamin A carotenoid oxidation products such as those derived from lycopene. However, biological effects of carotenoid oxidation products other than retinoids are only hypothesized in vivo in humans, which hypothesis has been used as the basic principle to justify in vitro studies of these compounds. 

Besides the capacity of CRTI to introduce all four double bonds in the conversion of phytoene to lycopene, the enzyme produces different geometric isomers than does PDS/ZDS (see graphic, side-by-side comparison in Fraser and Bramley ). CRTI produces all-trans isomers. Studies that have examined the function of the paired plant desaturases acting together, from Arabidopsis, and from maize and from... 

In a very recent study in potatoes, inhibition of LCYE accumulation was accomplished by an antisense LcyE driven by the patatin promoter and allowed rechanneling of lycopene toward the P-carotene branch of the pathway to produce up to 14-fold increased levels of P-carotene as well as up to 2.5-fold increased total carotenoids. RNAi and TILLING for manipulation of carotenogenesis have yet to be reported, but these new techniques for suppression of function and generation and selection of allelic diversity are likely to impact future research and production of varieties with enhanced pigment accumulation. 

An interlaboratory study using mixed vegetable reference material showed average relative standard deviations (RSDs) of 23% ranging from 11% for lutein and a-carotene to 40% for lycopene." Triplicate HPLC injections of the same extract showed RSD values of 0% for P-carotene and 6.8% for lutein. ... 

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