New Insights into Molecular Mechanism behind Anti-Cancer Activities of Lycopene

Lycopene is a well-known compound found commonly in tomatoes which brings wide range of health benefits against cardiovascular diseases and cancers. From an anti-cancer perspective, lycopene is often associated with reduced risk of prostate cancer and people often look for it as a dietary supplement which may help to prevent cancer. Previous scientific evidence exhibited that the anti-cancer activity of lycopene relies on its ability to suppress oncogene expressions and induce proapoptotic pathways. To further explore the real potential of lycopene in cancer prevention, this review discusses the new insights and perspectives on the anti-cancer activities of lycopene which could help to drive new direction for research. The relationship between inflammation and cancer is being highlighted, whereby lycopene suppresses cancer via resolution of inflammation are also discussed herein. The immune system was found to be a part of the anti-cancer system of lycopene as it modulates immune cells to suppress tumor growth and progression. Lycopene, which is under the family of carotenoids, was found to play special role in suppressing lung cancer.     

番茄红素化学合成的研究进展

番茄红素是一种广泛存在于自然界的特殊类胡萝卜素,具有较强的抗氧化活性和多种生理活性,对各种癌症具有一定的预防和抑制效果。本文综述了自番茄红素被发现以来的几种化学合成方法。参考文献15篇。     

Divergent optimum levels of lycopene,beta-carotene and lutein protecting against UVB irradiation in human fibroblastst

Exposure of living organisms to UV light leads to photooxidative reactions. Peroxyl radicals are involved in the propagation of lipid peroxidation. Carotenoids are dietary antioxidants and show photoprotective effects in human skin, efficiently scavenging peroxyl radicals and inhibiting lipid peroxidation. Cultured human skin fibroblasts were used to examine the protective effects of the carotenoids, lycopene, beta-carotene and lutein on UVB-induced lipid peroxidation. The carotenoids were delivered to the cells using liposomes as the vehicle. The cells were exposed to UVB light for 20 min. Lycopene, beta-carotene and lutein were capable of decreasing UV-induced formation of thiobarbituric acid-reactive substances at 1 h to levels 40-50% of controls free of carotenoids. The amounts of carotenoid needed for optimal protection were divergent at 0.05, 0.40 and 0.30 nmol/mg protein for lycopene, beta-carotene and lutein, respectively. Beyond the optimum levels, further increases of carotenoid levels in cells led to prooxidant effects.     

Cardiovascular Disease and Possible Ways in Which Lycopene Acts as an Efficient Cardio-Protectant against Different Cardiovascular Risk Factors

Foods rich in antioxidants such as lycopene have a major role in maintaining cardiac health. Lycopene, 80% of which can be obtained by consuming a common vegetable such as tomato, can prevent the disturbances that contribute to cardiovascular disease (CVD). The present work begins with a brief introduction to CVD and lycopene and its various properties such as bioavailability, pharmacokinetics, etc. In this review, the potential cardio-protective effects of lycopene that reduce the progression of CVD and thrombotic complications are detailed. Further, the protective effects of lycopene including in vitro, in vivo and clinical trials conducted on lycopene for CVD protective effects are explained. Finally, the controversial aspect of lycopene as a protective agent against CVD and toxicity are also mentioned.     

A simple and rapid method to assess lycopene in multiple layers of skin samples

Topical application of lycopene is a convenient way to restore antioxidants depleted from the skin by UV radiation and achieve protection against premature aging and cancer. In this study, a simple, rapid and reproducible method to quantify lycopene in different skin layers was developed, validated and employed to assess this compound after skin penetration studies. Lycopene was extracted from the stratum corneum (SC) and viable epidermis and dermis (ED) by vortex homogenization and bath sonication in a mixture of acetonitrile and methanol (52:48, v/v). Lycopene was assayed by HPLC using a C₁₈ column, and acetonitrile:methanol (52:48, v/v) as mobile phase. The quantification limit of lycopene in samples of SC and ED was 35 ng/mL and the assay was linear from 35 to 2000 ng/mL. Within‐day and between‐days assays coefficients of variation and relative errors (indicative of precision and accuracy) were less than 15% (or 20% for the limit of quantification). Lycopene recovery from SC and ED was dependent on the spiked concentration: for 50 ng/mL, recoveries were 88.3 and 90.5%; for 100–1000 ng/mL, recoveries were 68.6–74.9%. This method has a potential application for lycopene quantification during formulation development and evaluation in the dermatological field. Copyright © 2009 John Wiley & Sons, Ltd.     

Cancer chemoprevention by carotenoids

Carotenoids are natural fat-soluble pigments that provide bright coloration to plants and animals. Dietary intake of carotenoids is inversely associated with the risk of a variety of cancers in different tissues. Preclinical studies have shown that some carotenoids have potent antitumor effects both in vitro and in vivo, suggesting potential preventive and/or therapeutic roles for the compounds. Since chemoprevention is one of the most important strategies in the control of cancer development, molecular mechanism-based cancer chemoprevention using carotenoids seems to be an attractive approach. Various carotenoids, such as β-carotene, a-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, fucoxanthin, canthaxanthin and astaxanthin, have been proven to have anti-carcinogenic activity in several tissues, although high doses of β-carotene failed to exhibit chemopreventive activity in clinical trials. In this review, cancer prevention using carotenoids are reviewed and the possible mechanisms of action are described.     

Carotenoid Recovery from Tomato Processing By-Products through Green Chemistry

The recovery of bioactive compounds from agro-industry-derived by-products sustains circular economy principles by encouraging maximized recycling and minimized waste. Tomato processing by-products are abundant in carotenoids, which have several health-promoting properties, and their reintegration into functional food products represents a major interest for scientists and manufacturers. In the present study, carotenoids were recovered from tomato processing by-products based on the principles of green chemistry by using generally recognized as safe (GRAS) solvents, freeze-drying as pretreatment, and ultrasound in the recovery procedure. Spectrophotometric measurements and HPLC were used to identify and quantify total and individual carotenoids from the extracts. The highest values for lycopene (1324.89 µg/g dw) were obtained when ethyl lactate was applied as a solvent, followed by ethyl acetate with slightly smaller differences (1313.54 µg/g dw). The extracts obtained from freeze-dried samples presented significantly lower amounts of lycopene, indicating that carotenoids are highly susceptible to degradation during lyophilization. Flaxseed, grape seed, and hempseed oils were enriched with carotenoids and their rheological measurements showed favorable viscoelastic properties, especially hempseed and flaxseed oil, with viscosity under 50 mPa·s. Considering the results and the economic perspective of carotenoid recovery from tomato processing by-products, ethyl acetate is suitable, sustainable, and environmentally friendly for carotenoid extraction.     

Lycopene: A Potent Antioxidant for the Amelioration of Type II Diabetes Mellitus

Nutrition is of utmost importance in chronic disease management and has often been described as the cornerstone of a variety of non-communicable diseases. In particular, type II diabetes mellitus (T2DM) represents a prevalent and global public health crisis. Lycopene, a bright red carotenoid hydrocarbon found in tomatoes and other red fruits and vegetables, has been extensively studied for its biological activities and treatment efficiency in diabetes care. Epidemiological investigations indicate that lycopene has potential antioxidant properties, is capable of scavenging reactive species, and alleviates oxidative stress in T2DM patients. This review aims to summarize the characteristics and mechanisms of action of lycopene as a potent antioxidant for T2DM. In addition, the evidence demonstrating the effects of lycopene on glycemic control and oxidative stress biomarkers in T2DM are also highlighted using animal and human studies as literature approach.     

Bioactive Compounds and Antioxidant Capacity of Valencian Pepper Landraces

Sweet pepper is one of the most important economic fruits with nutritional attributes. In this sense, the nutraceutical value of consumed products is a major concern nowadays so the content of some bioactive compounds and antioxidants (phenols, ascorbic acid, lycopene, carotenoids, chlorophylls, and antioxidant activity) was monitored in 18 sweet pepper landraces at two maturity stages (green and red). All the traits except chlorophylls significantly increased in red fruits (between 1.5- and 2.3-fold for phenols, ascorbic acid, and 2-2-diphenyl-1-picrylhydrazyl (DPPH) inhibition activity, 4.8-fold for carotenoid and 27.4-fold for lycopene content), which suggests that ripening is key for obtaining desired fruit quality. Among landraces, P-44 in green fruits is highlighted for its content in carotenoids, chlorophylls, phenols, and ascorbic acid, and P-46 for its antioxidant capacity and lycopene content. Upon maturity, P-48, P-44, and P-41 presented higher levels of phenols and lycopene, and P-39 of phenols, carotenoid, and DPPH. This work reflects a wide variability in the 18 pepper landraces at bioactive compounds concentration and in relation to fruit ripeness. The importance of traditional landraces in terms of organoleptic properties is emphasized as they are the main source of agricultural biodiversity today and could be helpful for breeders to develop new functional pepper varieties.     

Application of analytical and preparative high-speed counter-current chromatography for separation of lycopene from crude extract of tomato paste

Lycopene was isolated from 100 mg of crude extract of tomato paste containing about 9% of lycopene. Analytical high-speed counter-current chromatography (HSCCC) was first used for the systematic selection of the two-phase solvent system. Then preparative HSCCC separation was performed with a nonaqueous solvent system composed of n-hexane-dichloromethane-acetonitrile at an optimum volume ratio of 10:3.5:6.5. This yielded 8.6 mg of lycopene at over 98.5% purity as determined by HPLC analysis.     

Analytical determination of antioxidants in tomato: typical components of the Mediterranean diet

Diets in the countries of the Mediterranean basin are characterised by abundant plant foods (fruits, vegetables, breads, nuts, seeds, wine, and olive oil) and include fish and low-fat dairy products. Among the vegetables, tomatoes are a main component of the traditional Mediterranean diet, which has been associated with health protection and longevity. Eating tomatoes has been associated with reduced risks of some types of cancer and other diseases. These beneficial properties appear to be related to the antioxidant content of the fruit, particularly carotenoids (lycopene and beta-carotene), ascorbic acid, and phenols, which may play a role in inhibiting reactions mediated by reactive oxygen species. Due to the importance of antioxidant compounds in tomatoes and tomato products, we present here an overview of current analytical methods (from 2000 until the present date) for determining the different antioxidants. The analytical procedures used to determine individual compounds involve extraction from the sample, analytical separation, and quantification. The choice of analytical method depends on the particular focus of the analysis and the kind of product analysed. High-performance liquid chromatography is the technique of choice for the analysis of tomato antioxidants.     

Direct determination of lycopene content in tomatoes (Lycopersicon esculentum) by attenuated total reflectance infrared spectroscopy and multivariate analysis

Lycopene is a potent antioxidant that has been shown to play critical roles in disease prevention. Efficient assays for detection and quantification of lycopene are desirable as alternatives to time- and labor-intensive methods. Attenuated total reflectance infrared (ATR-IR) spectroscopy was used for quantification of lycopene in tomato varieties. Calibration models were developed by partial least-squares regression (PLSR) using quantitative measures of lycopene concentration from liquid chromatography as reference method. IR spectra showed a distinct marker band at 957 cm(-1) for trans Carbon-Hydrogen (CH) deformation vibration of lycopene. PLSR models predicted the lycopene content accurately and reproducibly with a correlation coefficient (sigma) of 0.96 and standard error of cross-validation <0.80 mg/100 g. ATR-IR spectroscopy allowed for rapid, simple, and accurate determination of lycopene in tomatoes with minimal sample preparation. Results suggest that the ATR-IR method is applicable for high-throughput quantitative analysis and screening for lycopene in tomatoes.     

Antioxidant inhibition of porphyrin-induced cellular phototoxicity.

Porphyrins such as protoporphyrin IX (PP IX) and uroporphyrin I (UP I) can be phototoxic to human cells. To study the protective ability of antioxidants (beta-carotene, lycopene, ascorbic acid and alpha-tocopherol), against such porphyrin phototoxicity, membrane destruction experiments (Jurkat cells) and human cell cultures (fibroblasts) were performed. Both beta-carotene and lycopene and also the combination of beta-carotene, ascorbic acid and alpha-tocopherol offered cell protection against PP IX phototoxicity. Investigations of both cell membrane protection and of cell growth showed differences in terms of the protection afforded by the anti-oxidants. Thus, for PP IX, carotenoids alone, and in combination with ascorbic acid and alpha-tocopherol, showed higher protection factors in general than UP I. However, for membrane protection there was significant protection against UP I by the combination of beta-carotene, ascorbic acid and alpha-tocopherol but not by any of these anti-oxidants alone. The membrane protection against PP IX by beta-carotene, and especially lycopene, is significant presumably because of the high lipophilicity of all these molecules. However, the hydrophilic UP I will cause phototoxicity mainly via H(2)O(2), radical or singlet oxygen production in the aqueous phase, and these reactive species may be generated some distance from the cell membrane. This may lead to the little or no protection observed for UP I by the individual antioxidants. Nevertheless, a combination of beta-carotene, ascorbic acid and alpha-tocopherol offers membrane protection against the phototoxicity of both porphyrins. This is believed to occur as a result of synergistic processes. Our results suggest that the treatment of porphyria cutanea tarda and erythropoietic protoporphyria may be improved by the use of a combination of the antioxidants studied.     

Lycopene Inhibits Toll-Like Receptor 4-Mediated Expression of Inflammatory Cytokines in House Dust Mite-Stimulated Respiratory Epithelial Cells

House dust mites (HDM) are critical factors in airway inflammation. They activate respiratory epithelial cells to produce reactive oxygen species (ROS) and activate Toll-like receptor 4 (TLR4). ROS induce the expression of inflammatory cytokines in respiratory epithelial cells. Lycopene is a potent antioxidant nutrient with anti-inflammatory activity. The present study aimed to investigate whether HDM induce intracellular and mitochondrial ROS production, TLR4 activation, and pro-inflammatory cytokine expression (IL-6 and IL-8) in respiratory epithelial A549 cells. Additionally, we examined whether lycopene inhibits HDM-induced alterations in A549 cells. The treatment of A549 cells with HDM activated TLR4, induced the expression of IL-6 and IL-8, and increased intracellular and mitochondrial ROS levels. TAK242, a TLR4 inhibitor, suppressed both HDM-induced ROS production and cytokine expression. Furthermore, lycopene inhibited the HDM-induced TLR4 activation and cytokine expression, along with reducing the intracellular and mitochondrial ROS levels in HDM-treated cells. These results collectively indicated that the HDM induced TLR4 activation and increased intracellular and mitochondrial ROS levels, thus resulting in the induction of cytokine expression in respiratory epithelial cells. The antioxidant lycopene could inhibit HDM-induced cytokine expression, possibly by suppressing TLR4 activation and reducing the intracellular and mitochondrial ROS levels in respiratory epithelial cells.     

Lycopene control of benzophenone-sensitized lipid peroxidation

Lycopene antioxidant activity in the presence of two different mixtures of phospholipids in hexane solution, under continuous regime of UV-irradiation from three different ranges (UV-A, UV-B, and UV-C) has been evaluated in this work. Lycopene expected role was to control lipid peroxidation, by scavenging free radicals generated by UV-irradiation, in the presence and in the absence of selected photosensitizer, benzophenone. This work shows that lycopene undergoes to UV-induced destruction (bleaching), highly dependent on the incident photons energy input, more expressed in the presence than in the absence of benzophenone. The further increase (“excess”) of its bleaching is undoubtedly related to the further increase of its antioxidant activity in the presence of benzophenone, having the same cause: increase of (phospholipids peroxidation) chain-breaking activities.     

Optimization and development of a high‐performance liquid chromatography method for the simultaneous determination of vitamin E and carotenoids in tomato fruits

A simple and reliable high‐performance liquid chromatography method was developed and validated for the simultaneous determination of lipophilic antioxidants in tomato fruits using C₃₀ column operated at 15°C and a gradient mobile phase based on acetonitrile/methanol/dichloromethane in a total run time of 30 min. Diode array and fluorescence detectors were used respectively for the detection of carotenoids (lutein, zeaxanthin, cryptoxanthin, lycopene, and β‐carotene) and vitamin E analogs (α‐, β‐, γ‐, and δ‐tocopherols, and tocotrienols). The best extraction yield of analytes in tomato fruits was achieved by employing ethyl acetate/hexane (1:1, v/v) after several treatments with various solvents. In addition, low extraction yields were obtained for carotenoids compared to tocopherols by adopting solid‐phase extraction as a second clean‐up step. The method was validated on the basis of recovery, precision, linearity, and limit of detection and quantification using spiked tomato samples. The method was applied to cherry and medium‐sized tomato fruits. Lycopene was found to be present in largest amount in tomato pulp, followed by β‐carotene and lutein. Due to its simplicity, rapidity, and efficiency, the method is suitable for routine analysis of lipophilic antioxidants in tomato fruits, and may also be applied to other vegetables of similar phytochemical profiles.     

Degradation kinetic (D100) of lycopene during the thermal treatment of concentrated tomato paste

Heat treatments can cause degradation in tomatoes of lycopene which has important antioxidant effects. No information about decimal reduction time (D₁₀₀) of lycopene is available. D-value is the time required at a given temperature to reduce 90% of the molecule. This study for the first time determine the kinetic of lycopene thermal degradation. The content was measured at regular intervals of pasteurization using canned tomato paste to determinate D value. Microbiological analysis was carried out to verify product stability after packaging. Yeasts, molds and lactic acid bacteria were determined. The pasteurization time allowed to observe a loss of the red color. Lycopene content, after an increase at 8 min, decreased at 32 min of pasteurization. D₁₀₀ value was calculated at 75 min; a diminution of 90% in lycopene content in the concentrated tomato paste was observed. Microbiological analysis confirmed the stability of products after 8 min of pasteurization.     

Chili Pepper Carotenoids: Nutraceutical Properties and Mechanisms of Action

Chili pepper is a prominent cultivated horticultural crop that is traditionally used for food seasoning and is applied for the treatment and prevention of multiple diseases. Its beneficial health properties are due to its abundance and variety of bioactive components, such as carotenoids, capsaicinoids, and vitamins. In particular, carotenoids have important nutraceutical properties, and several studies have focused on their potential in the prevention and treatment of human diseases. In this article, we reviewed the state of knowledge of general aspects of chili pepper carotenoids (biosynthesis pathway, types and content in Capsicum spp., and the effects of processing on carotenoid content) and recent findings on the effects of carotenoid nutraceuticals, such as antioxidant, cancer preventive, anti-inflammatory, cardiovascular disorder preventive, and anti-obesity effects.     

Dietary uptake of lycopene protects human cells from singlet oxygen and nitrogen dioxide - ROS components from cigarette smoke.

There is current interest in the health benefits of dietary carotenoids and the possible deleterious effects on certain sub-populations such as smokers. Here we report in vivo protection of human lymphocytes, conferred by dietary supplementation of lycopene rich foods against the reactive oxygen species, NO(2)(*) radical (by electron transfer) and 1(O)(2) (by energy transfer). It was found that a lycopene rich diet, maintained for 14 days, increased the serum lycopene level 10 fold compared to serum obtained after the same period, where a typical western European diet had been consumed. Relative lymphocyte protection factors of 17.6 and 6.3 against NO(2)(*) radical and 1(O)(2), respectively, were obtained, which re-enforce epidemiological data, showing protection against several chronic diseases by tomato lycopene.     

Carotene location in processed food samples measured by cryo In-SEM Raman

Cryo In-SEM Raman has been used for the first time to localise carotene compounds in a food matrix. Raman spectra of lycopene and β-carotene have been obtained from sampling oil droplets and plant cell structures visualised with cryo-SEM in tomato and carrot based emulsions containing 5% oil. It was possible to identify the carotenoids in both the oil droplets and the cell walls. Furthermore our results gave some indication that the carotenoids were in the non-crystalline state. It has been suggested that a higher amount of carotenes solubilised into the oil phase of the food matrix would lead to a higher bioaccessibility, thus understanding the effect of processing conditions on micronutrients distribution in a food matrix might help the design of plant based food products with a better nutritional quality. This shows improved structural characterisation of the cryo-SEM with the molecular sensitivity of Raman spectroscopy as a promising approach for complex biological problems.