Multifaceted Effects of Lycopene: A Boulevard to the Multitarget-Based Treatment for Cancer

Lycopene is a pigment belonging to the group of carotenoids and it is among the most carefully studied antioxidants found especially in fruit and vegetables. As a carotenoid, lycopene exerts beneficial effects on human health by protecting lipids, proteins, and DNA from damage by oxidation. Lycopene is a powerful oxygen inactivator in the singlet state. This is suggestive of the fact that lycopene harbors comparatively stronger antioxidant properties over other carotenoids normally present in plasma. Lycopene is also reported to hinder cancer cell proliferation. The uncontrolled, rapid division of cells is a characteristic of the metabolism of cancer cells. Evidently, lycopene causes a delay in the progression of the cell cycle, which explains its antitumor activity. Furthermore, lycopene can block cell transformation by reducing the loss of contact inhibition of cancer cells. This paper collects recent studies of scientific evidence that show the multiple beneficial properties of lycopene, which acts with different molecular and cellular mechanisms.     

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。     

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.     

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.     

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.     

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.     

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.     

Sustainable Valorization of Tomato By-Products to Obtain Bioactive Compounds: Their Potential in Inflammation and Cancer Management

Tomato producing and processing industries present undoubted potential for industrial discarded products valorization whether due to the overproduction of fresh tomatoes or to the loss during processing. Although tomato by-products are not yet considered a raw material, several studies have suggested innovative and profitable applications. It is often referred to as “tomato pomace” and is quite rich in a variety of bioactive compounds. Lycopene, vitamin C, β-carotene, phenolic compounds, and tocopherol are some of the bioactives herein discussed. Tomato by-products are also rich in minerals. Many of these compounds are powerful antioxidants with anti-inflammatory properties besides modulating the immune system. Several researchers have focused on the possible application of natural ingredients, especially those extracted from foods, and their physiological and pharmacological effects. Herein, the effects of processing and further applications of the bioactive compounds present in tomato by-products were carefully reviewed, especially regarding the anti-inflammatory and anti-cancer effects. The aim of this review was thus to highlight the existing opportunities to create profitable and innovative applications for tomato by-products in health context.     

Chromatographic determination of the effect of storage on lycopene

A reverse-phase high-performance liquid chromatography (HPLC) method for the determination of lycopene in an alkaline lipid phase is described, and pigment stability in stored tomato sausage is reported. To avoid and replace the use of nitrite, lycopene from tomato products is added to minced meat and a tomato sausage with natural color is produced. Tomato sausage with and without nitrite were smoked in a smoking compartment and stored (4 degrees C and 8 degrees C) for 25 and 17 days, respectively. Among other factors, the quality of the tomato sausage depends on stability of lycopene during process and storage. Lycopene, being lipophilic, is extracted together with the polar and neutral fat in food. Efforts to purify lycopene from the fatty content will result in loss of pigment. The triacylglycerides obstruct the detection of lycopene by spectrophotometry or by HPLC with diode-array detection. To solve this problem, the triacylglycerides are hydrolyzed to free fatty acids just before analyzing lycopene on a column tolerating alkaline samples. At the end of the storage, loss of pigment in the sausage without nitrite was 26% stored at 4 degrees C and 19% at 8 degrees C. Corresponding results for the sausage with nitrite added as well as tomato paste show the loss of pigment is 20% and 45%. For each type of fatty food extracted, it is important to minimize the use of alkaline solutions because the HPLC equipment may be susceptible to alkaline conditions.     

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.     

番茄红素对镉诱导睾丸损伤大鼠抗氧化酶活性及生殖激素水平的影响

目的观察番茄红素对镉诱导睾丸损伤大鼠抗氧化酶活性及生殖激素水平的影响。方法将28只雄性SD大鼠随机分为4组,每组7只,分别为空白对照组、5 mg/L镉组、5 mg/L镉+10 mg/kg番茄红素组、5 mg/L镉+20 mg/kg番茄红素组,给药1周后处死,测定睾丸组织超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)活性及血清促黄体生成素(LH)、睾酮(T)水平。结果镉组大鼠体质量、睾丸质量、睾丸组织SOD、GSH-Px活性及血清T水平均显著低于NC组(P0.01),睾丸组织MDA含量和血清LH水平则显著高于后者(P0.01);番茄红素可缓解染镉大鼠体质量和睾丸质量的减轻,并回调抗氧化酶活性和生殖激素水平,且高剂量组效果更为显著。结论番茄红素对染镉大鼠的睾丸损伤具有剂量依赖性的改善作用,可能与清除氧自由基和抗脂质过氧化有关。     

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.     

Advances in Management of Bladder Cancer—The Role of Photodynamic Therapy

Photodynamic therapy (PDT) is a non-invasive and modern form of therapy. It is used in the treatment of non-oncological diseases and more and more often in the treatment of various types of neoplasms in various locations including bladder cancer. The PDT method consists of local or systemic application of a photosensitizer, i.e., a photosensitive compound that accumulates in pathological tissue. Light of appropriate wavelength is absorbed by the photosensitizer molecules, which in turn transfers energy to oxygen or initiates radical processes that leads to selective destruction of diseased cells. The technique enables the selective destruction of malignant cells, as the photocytotoxicity reactions induced by the photosensitizer take place strictly within the pathological tissue. PDT is known to be well tolerated in a clinical setting in patients. In cited papers herein no new safety issues were identified. The development of anti-cancer PDT therapies has greatly accelerated over the last decade. There was no evidence of increased or cumulative toxic effects with each PDT treatment. Many modifications have been made to enhance the effects. Clinically, bladder cancer remains one of the deadliest urological diseases of the urinary system. The subject of this review is the anti-cancer use of PDT, its benefits and possible modifications that may lead to more effective treatments for bladder cancer. Bladder cancer, if localized, would seem to be a good candidate for PDT therapy since this does not involve the toxicity of systemic chemotherapy and can spare normal tissues from damage if properly carried out. It is clear that PDT deserves more investment in clinical research, especially for plant-based photosensitizers. Natural PS isolated from plants and other biological sources can be considered a green approach to PDT in cancer therapy. Currently, PDT is widely used in the treatment of skin cancer, but numerous studies show the advantages of related therapeutic strategies that can help eliminate various types of cancer, including bladder cancer. PDT for bladder cancer in which photosensitizer is locally activated and generates cytotoxic reactive oxygen species and causing cell death, is a modern treatment. Moreover, PDT is an innovative technique in oncologic urology.     

Erythrocyte-derived drug delivery systems in cancer therapy

As natural blood components,erythrocytes were good candidates for being used as drug delive ry systems to improve the pharmacokinetics,biocompatibility and many other aspects of different drugs.The advantages brought by erythrocytes making erythrocyte-derived drug delivery systems,also known as erythrocyte carriers,suitable for various anti-cancer agents,especially newly invented agents like nanoparticles,which were characterized by their undesired systematic toxicity,anaphylactic reactions and poor biocompatibility.Current researches on erythrocyte carriers in ca ncer therapy showed inspiring results in four major aspects:cancer enzyme therapy,delivering chemotherapeutic agents,combining with nanoparticles,and several other anti-cancer agents for gene or immune therapy.This novel delivering system was now undergoing the translation process from laboratory to clinical practice.Erythrocyte carriers for cancer enzyme therapy have entered the stage of clinical trial and have showed promising outcomes,and others were still at pre-clinical stage.In summary,erythrocyte-derived drug delivery system might play an indispensable role in the management of cancer in the future.     

Optisch aktive Lycopin-epoxide und Lycopin-glycole: Synthesen und chiroptische Eigenschaften

Optically Active Lycopene Epoxides and Lycopene Glycols: Synthesis and Chiroptical Properties We present extensive spectral and chiroptical data on the pure and crystalline lycopene diepoxides 1–3 and glycols 4–9 . A first synthetic approach to 1–9 with (+)-malic acid as starting material afforded 30 as a complex mixture of isomers (Scheme 1). Pure stereoisomers 1–9 were obtained using the enantiomerically pure epoxygeraniol 31 as starting material (Scheme 2). Differentiation of the (5Z)-from the (all-E)-isomers by ¹H-NMR and UV/VIS alone is very difficult.     

番茄红素改善移植血管内皮功能

目的探讨番茄红素对大鼠移植血管内皮功能的改善作用。方法实验分为两组:实验组,Lewis大鼠接受Brown-Norway(BN)大鼠腹主动脉移植;番茄红素干预组(30 mg·kg-1·d-1),Lewis大鼠接受BN大鼠腹主动脉移植。于移植后28 d取移植动脉,进行组织形态学观察、测量内膜厚度,免疫组化检测血管内i NOS和ICAM-1表达。收集各组血浆,ELISA检测c GMP浓度。结果各组血管内膜均出现增厚;番茄红素干预组血管内膜增厚与实验组相比显著降低,差异有统计学意义(P0.05)。免疫组化检测结果显示,与实验组相比,番茄红素干预组移植动脉i NOS表达增高(P0.05)。结论番茄红素通过调控NOS通路,改善内皮功能,缓解移植动脉的纤维化进程以及内膜的增生。     

A Review on Cancer Immunotherapy and Applications of Nanotechnology to Chemoimmunotherapy of Different Cancers

Clinically, different approaches are adopted worldwide for the treatment of cancer, which still ranks second among all causes of death. Immunotherapy for cancer treatment has been the focus of attention in recent years, aiming for an eventual antitumoral effect through the immune system response to cancer cells both prophylactically and therapeutically. The application of nanoparticulate delivery systems for cancer immunotherapy, which is defined as the use of immune system features in cancer treatment, is currently the focus of research. Nanomedicines and nanoparticulate macromolecule delivery for cancer therapy is believed to facilitate selective cytotoxicity based on passive or active targeting to tumors resulting in improved therapeutic efficacy and reduced side effects. Today, with more than 55 different nanomedicines in the market, it is possible to provide more effective cancer diagnosis and treatment by using nanotechnology. Cancer immunotherapy uses the body’s immune system to respond to cancer cells; however, this may lead to increased immune response and immunogenicity. Selectivity and targeting to cancer cells and tumors may lead the way to safer immunotherapy and nanotechnology-based delivery approaches that can help achieve the desired success in cancer treatment.     

An Insight into the Anti-Angiogenic and Anti-Metastatic Effects of Oridonin: Current Knowledge and Future Potential

Cancer is one of the leading causes of death worldwide, with a mortality rate of more than 9 million deaths reported in 2018. Conventional anti-cancer therapy can greatly improve survival however treatment resistance is still a major problem especially in metastatic disease. Targeted anti-cancer therapy is increasingly used with conventional therapy to improve patients’ outcomes in advanced and metastatic tumors. However, due to the complexity of cancer biology and metastasis, it is urgent to develop new agents and evaluate the anti-cancer efficacy of available treatments. Many phytochemicals from medicinal plants have been reported to possess anti-cancer properties. One such compound is known as oridonin, a bioactive component of Rabdosia rubescens. Several studies have demonstrated that oridonin inhibits angiogenesis in various types of cancer, including breast, pancreatic, lung, colon and skin cancer. Oridonin’s anti-cancer effects are mediated through the modulation of several signaling pathways which include upregulation of oncogenes and pro-angiogenic growth factors. Furthermore, oridonin also inhibits cell migration, invasion and metastasis via suppressing epithelial-to-mesenchymal transition and blocking downstream signaling targets in the cancer metastasis process. This review summarizes the recent applications of oridonin as an anti-angiogenic and anti-metastatic drug both in vitro and in vivo, and its potential mechanisms of action.     

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.     

Potent Lymphatic Translocation and Spatial Control Over Innate Immune Activation by Polymer–Lipid Amphiphile Conjugates of Small‐Molecule TLR7/8 Agonists

Uncontrolled systemic inflammatory immune triggering has hampered the clinical translation of several classes of small‐molecule immunomodulators, such as imidazoquinoline TLR7/8 agonists for vaccine design and cancer immunotherapy. By taking advantage of the inherent serum‐protein‐binding property of lipid motifs and their tendency to accumulate in lymphoid tissue, we designed amphiphilic lipid–polymer conjugates that suppress systemic inflammation but provoke potent lymph‐node immune activation. This work provides a rational basis for the design of lipid–polymer amphiphiles for optimized lymphoid targeting.