Natural sulforaphane as a functional chemopreventive agent: including a review of isolation, purification and analysis methods

Epidemiological data show that a diet rich in fruits and vegetables can reduce the risk from a number of cancers and chronic diseases. Sulforaphane (SF), a phytochemical constituent of cruciferous vegetables, has been widely researched in recent decades as a potential chemopreventive compound. Nonexistent in intact vegetables, natural SF, is formed from glucoraphanin hydrolyzed by myrosinase. This review summarizes and compares different analysis, isolation and purification methods engaged in SF research. Major important chemopreventive properties of SF investigated in existing research are reviewed and discussed, including antioxidant, anticarcinogenic and anti-inflammatory functions. Considering the potential applications of SF in the future, metabolism, stability and formulation developments of SF are also discussed. Research opportunities are identified based on the review of existing studies to facilitate future explorations on SF, a promising natural compound in chemopreventive therapy.     

The role of Sulforaphane in cancer chemoprevention and health benefits: a mini-review

Cancer is a multi-stage process resulting from aberrant signaling pathways driving uncontrolled proliferation of transformed cells. The development and progression of cancer from a premalignant lesion towards a metastatic tumor requires accumulation of mutations in many regulatory genes of the cell. Different chemopreventative approaches have been sought to interfere with initiation and control malignant progression. Here we present research on dietary compounds with evidence of cancer prevention activity that highlights the potential beneficial effect of a diet rich in cruciferous vegetables. The Brassica family of cruciferous vegetables such as broccoli is a rich source of glucosinolates, which are metabolized to isothiocyanate compounds. Amongst a number of related variants of isothiocyanates, sulforaphane (SFN) has surfaced as a particularly potent chemopreventive agent based on its ability to target multiple mechanisms within the cell to control carcinogenesis. Anti-inflammatory, pro-apoptotic and modulation of histones are some of the more important and known mechanisms by which SFN exerts chemoprevention. The effect of SFN on cancer stem cells is another area of interest that has been explored in recent years and may contribute to its chemopreventive properties. In this paper, we briefly review structure, pharmacology and preclinical studies highlighting chemopreventive effects of SFN.     

十字花科植物中莱菔硫烷防癌机制研究进展

十字花科蔬菜中的异硫氰酸酯--莱菔硫烷(sulforaphane,SF)可以在癌症的起始、发展和增生3个阶段阻滞癌细胞的生长发育,降低癌症发生的风险,其前体物主要存在于西兰花中.本文主要对国内外近年来有关SF对化学致癌物代谢酶的影响、激活抗氧化基因活性、激活转录因子、阻滞细胞周期、诱导细胞凋亡等方面的研究进展进行综述,以探讨SF的防癌机制,为防癌抗癌食品和药物的研发提供参考.     

Modulation of inflammatory signaling pathways by phytochemicals in ovarian cancer

Inflammation has been suggested to be involved in cancer development and progression. Many clinical and experimental studies have shown that inflammation could contribute to ovarian carcinogenesis through activation of the NF-κB and AP-1 pathways by chronic inflammatory mediators. Phytochemicals, which are natural compounds derived from fruits and vegetables, have shown anti-inflammatory and anti-cancer effects. Due to their relatively low toxicity and easy accessibility, phytochemicals have been investigated for their chemopreventive potential against various cancers. In this review, we discuss the role of phytochemicals in preventing ovarian cancer through anti-inflammatory mechanisms.     

天然产物产生菌自抗性中DNA损伤修复的研究进展

临床上使用的抗生素大多是由微生物次级代谢产生的天然产物及其衍生物,这类化合物可以抑制微生物的生长,具有显著的细胞毒性。产生菌在合成这些抗生素的同时,也需要通过多种自抗性机制来应对其对自身的毒害作用。本文总结了近年来DNA损伤修复途径参与的天然产物产生菌自抗性机制的研究进展,重点介绍了DNA损伤类抗生素产生菌中的碱基切除修复途径和类核苷酸切除修复途径等,并对目前DNA损伤修复抗性机制中存在的问题进行了讨论,同时对其潜在的应用进行了展望。     

Metal and metalloid containing natural products and a brief overview of their applications in biology,biotechnology and biomedicine

Bioinorganic natural product chemistry is a relatively unexplored but rapidly developing field with enormous potential for applications in biology, biotechnology (especially in regards to nanomaterial development, synthesis and environmental cleanup) and biomedicine. In this review the occurrence of metals and metalloids in natural products and their synthetic derivatives are reviewed. A broad overview of the area is provided followed by a discussion on the more common metals and metalloids found in natural sources, and an overview of the requirements for future research. Special attention is given to metal hyperaccumulating plants and their use in chemical synthesis and bioremediation, as well as the potential uses of metals and metalloids as therapeutic agents. The potential future applications and development in the field are also discussed.     

海草种子特性与海草床修复

海草床面积的急剧减少已引起人们对海草床生态修复的重视, 种子在海草床修复中具有较大的应用潜力。该文系统归纳了近年来有关海草种子的研究概况及其应用进展: 从种子生物学和生态学角度对海草种子的形态结构、发育、散布、休眠和萌发进行了归纳比较; 提出了在研究天然海草种子库的同时, 有必要建立人工海草种子库的观点, 并指出建立和完善人工海草种子库需基于种子生物学和生态学研究, 以指导种子的采集和保存; 对海草种子的播种方式和利用种子修复海草床的途径进行了阐述, 并指出了目前研究和应用中存在的一系列问题。最后对海草种子的研究和应用前景进行了展望, 提出海草种子生态学将成为今后的研究热点, 在应用方面, 仍然需要以提高种子萌发率和成苗率为研究重点, 并指出如果利用由种子获得的人工幼苗进行海草床修复, 需首先解决幼苗成活率低的难题。     

The use of the micronucleus test on exfoliated cells to identify anti-clastogenic action in humans: a biological marker for the efficacy of chemopreventive agents.

Laboratory and epidemiological studies support the hypothesis that cancer incidence in human populations can be reduced by supplementing high-risk individuals with chemopreventive agents. Many candidate agents have been identified, too many to be assayed in long-term clinical trials. As an alternate approach, intermediate markers are currently being evaluated as short-term screens for the activity of chemopreventive agents in humans. These markers quantify cellular and molecular changes of biological significance to the process of carcinogenesis. One such marker is the micronucleus test on exfoliated cells. This assay has been used to quantify chromosomal breakage occurring in the human oral cavity, esophagus, cervix, lung, nasal cavity and urinary bladder. Intervention trials on high-risk populations have shown that supplementation with chemopreventive agents can modulate this breakage. This article will review the evidence in support of the use of this assay as a biological marker for the efficacy of a chemopreventive regime. Basic problem areas in the design and conduct of this assay in humans will also be discussed, as will the future potential of the assay.     

Bioconversion of natural gas to liquid fuel: Opportunities and challenges

Natural gas is a mixture of low molecular weight hydrocarbon gases that can be generated from either fossil or anthropogenic resources. Although natural gas is used as a transportation fuel, constraints in storage, relatively low energy content (MJ/L), and delivery have limited widespread adoption. Advanced utilization of natural gas has been explored for biofuel production by microorganisms. In recent years, the aerobic bioconversion of natural gas (or primarily the methane content of natural gas) into liquid fuels (Bio-GTL) by biocatalysts (methanotrophs) has gained increasing attention as a promising alternative for drop-in biofuel production. Methanotrophic bacteria are capable of converting methane into microbial lipids, which can in turn be converted into renewable diesel via a hydrotreating process. In this paper, biodiversity, catalytic properties and key enzymes and pathways of these microbes are summarized. Bioprocess technologies are discussed based upon existing literature, including cultivation conditions, fermentation modes, bioreactor design, and lipid extraction and upgrading. This review also outlines the potential of Bio-GTL using methane as an alternative carbon source as well as the major challenges and future research needs of microbial lipid accumulation derived from methane, key performance index, and techno-economic analysis. An analysis of raw material costs suggests that methane-derived diesel fuel has the potential to be competitive with petroleum-derived diesel.     

Chemopreventive compounds—View from the other side

Increasing attention is being paid to the possibility of applying chemopreventive agents for the protection of individuals from cancer risk. The beneficial potential of chemoprotective compounds is usually well documented by extensive experimental data. To assure the desired effect, these compounds are frequently concentrated to produce dietary supplements for human use. The additive and synergistic effects of other food constituents are, however, frequently ignored. Even natural chemopreventive compounds have to be considered as xenobiotics. Thus, as much attention has to be paid to their testing prior to their wide application as is usual in drug development for human treatment. Unfortunately, much of the research in this area is solely based on simplified in vitro systems that cannot take into account the complexity of biotransformation processes, e.g. chemopreventive compound-drug interaction, effect on metabolism of endogenic compounds. Hence, the predicted chemopreventive potential is not attained in respect of cancer prevention; moreover, the administration of high doses of chemopreventive compounds might be even detrimental for the human health.     

Seasonal variation of natural products in European trees

The present review gives an overview about the status of research on seasonal variation of natural products in European trees. Due to their different life forms, gymnosperms, deciduous angiosperms, and evergreen angiosperms are reviewed separately. Besides trying to give an overview about the existing newer literature, the review tries to define some repetitively found trends and discusses some possible explanations for these trends. Moreover, open research questions are highlighted and some suggestions for future studies are given. These suggestions encompass both subjects and desirable quality standards with regards to experimental designs. The reviewed publications are mainly focused on leaves, some on fruits, and some on barks and twigs. Phenolics, including phenolic acids and flavonoids of different types as well as tannins, are the most often studied compound class; additionally, some papers assess seasonal variation of alkaloids, diterpenes, essential oils, lignans, simple organic acid, secoiridoids, and stilbenoids.     

Anthocyanins: from plant to health

Anthocyanins are a group of natural occurring pigments responsible for the red-blue colour of many fruits and vegetables. Anthocyanins are of interest for two reasons because they cannot only be used in the technological field as natural colorants but also have important implications in the field of human health. Numerous studies indicate the potential effect that this family of flavonoids may have in reducing the incidence of cardiovascular disease, cancer, hyperlipidemias and other chronic diseases through the intake of anthocyanin-rich foods. This review examines existing literature in this area: from plant content and distribution to health implications, including the effect of agronomic and genetic modifications on the anthocyanin content of plants as well as other biotechnological factors and food processing. The bioavailability, metabolism, bioactivity, and epidemiology of anthocyanins will also be reviewed.     

Role of 4-hydroxynonenal in chemopreventive activities of sulforaphane

Chemoprevention of cancer via herbal and dietary supplements is a logical approach to combating cancer and currently it is an attractive area of research investigation. Over the years, isothiocyanates, such as sulforaphane (SFN) found in cruciferous vegetables, have been advocated as chemopreventive agents, and their efficacy has been demonstrated in cell lines and animal models. In vivo studies with SFN suggest that in addition to protecting normal healthy cells from environmental carcinogens, it also exhibits cytotoxicity and apoptotic effects against various cancer cell types. Among several mechanisms for the chemopreventive activity of SFN against chemical carcinogenesis, its effect on drug-metabolizing enzymes that cause activation/neutralization of carcinogenic metabolites is well established. Recent studies suggest that SFN exerts its selective cytotoxicity to cancer cells via reactive oxygen species-mediated generation of lipid peroxidation products, particularly 4-hydroxynonenal (HNE). Against the background of the known biochemical effects of SFN on normal and cancer cells, in this article we review the underlying molecular mechanisms responsible for the overall chemopreventive effects of SFN, focusing on the role of HNE in these mechanisms, which may also contribute to its selective cytotoxicity to cancer cells.     

天然抗氧化剂对ONOO~-损伤的抑制效应

过氧亚硝基阴离子(ONOO-)是生物体内产生的一种强氧化剂和细胞毒性物质。它可以介导生物大分子(包括DNA、蛋白质和脂质)的修饰与损伤。本文着重介绍四类主要的天然抗氧化剂——生物碱、多酚、多糖以及萜类抗氧化剂及其抑制ONOO-损伤的研究进展,并对未来的研究作了展望。     

孢粉素的物理化学性质和生物医学应用研究进展*

孢粉素是类聚乙烯醇链通过酯键和缩醛高度交联的天然生物高分子,构成花粉和孢子的外壁,能够抵抗物理、化学、生物腐蚀,堪称自然界最坚固的有机物,被誉为植物界的金刚石。孢粉素微囊(SEC)自然界来源丰富、生物相容性好、无免疫原性,表面含有丰富的羧基、羟基和酚基,能够功能化或者与其他纳米材料构建复合材料;其表面丰富的纳米孔道增加了材料的比表面积,有利于捕获癌细胞或目标生物分子。SEC独特的性质使其在药物载体、口服疫苗载体、影像诊断、生物传感、细胞生长支架、微反应器、微型机器人等方面得到广泛的应用。阐述了孢粉素的结构、物理化学性质、制备方法和功能化方面的研究进展, 探讨了孢粉素的应用前景、存在的问题以及未来的发展方向。     

Natural product inhibitors of ovarian neoplasia.

The present work constitutes a review of the literature on natural products with potential antitumor activity against ovarian neoplasias. The review refers to five plant extracts and sixty-nine compounds isolated from higher plants and microorganisms, which are classified in appropriate chemical groups and model tested, and cites their activity. Some aspects of recent research with natural products directed to ward producing drugs which are inhibitors of ovarian neoplasia are discussed.     

Hepatocyte growth factor/scatter factor and prostate cancer: a review

Men who die from prostate cancer do so from uncontrolled metastatic disease. A better understanding of the mechanisms involved in the progression and metastasis of prostate cancer may lead to novel therapeutic approaches to prevent its natural progression. Hepatocyte Growth Factor / Scatter factor (HGF/SF) has been demonstrated to elicit a number of key functions in numerous tissues that are important in the progression, invasion and metastasis of cancer. Studies have demonstrated that the activity of HGF/SF and its receptor c-Met are linked to disease progression in numerous cancers. However, research into these functions, which include activities as a mitogen, a motogen and an anti-apoptotic and angiogenic factor in prostate cancer are limited. This article reviews the published evidence of the roles HGF/SF plays in prostate cancer progression and highlights the clinical and therapeutic potential of research into this pleiomorphic cytokine.     

Sulforaphane as an inducer of glutathione prevents oxidative stress-induced cell death in a dopaminergic-like neuroblastoma cell line

The total GSH depletion observed in the substantia nigra (SN) appears to be responsible for subsequent oxidative stress (OS), mitochondrial dysfunction, and dopaminergic cell loss in patients with Parkinson's disease. A strategy to prevent the OS of dopaminergic cells in the SN may be the use of chemopreventive agents as inducers of endogenous GSH, antioxidant and phase 2 enzymes. In this study, we demonstrated that treatment of the dopaminergic-like neuroblastoma SH-SY5Y cell line with sulforaphane (SF), a cruciferous vegetables inducer, resulted in significant increases of total GSH level, NAD(P)H : quinone oxidoreductase-1, GSH-transferase and -reductase, but not GSH-peroxidase, catalase and superoxide dismutase activities. Further, the elevation of GSH levels, GSH-transferase and NAD(P)H:quinone oxidoreductase-1 activities was correlated to an increase of the resistance of SH-SY5Y cells to toxicity induced by H₂O₂ or 6-hydroxydopamine (6-OHDA). The pre-treatment of SH-SY5Y cells with SF was also shown to prevent various apoptotic events (mitochondrial depolarization, caspase 9 and 3 activation and DNA fragmentation) and necrosis elicited by 6-OHDA. Further, the impairment of antioxidant capacity and reactive oxygen species formation at intracellular level after exposure to 6-OHDA was effectively counteracted by pre-treatment with SF. Last, both the cytoprotective and antioxidant effects of SF were abolished by the addition of buthionine sulfoximine supporting the main role of GSH in the neuroprotective effects displayed by SF. These findings show that SF may play a role in preventing Parkinson's disease.