Biodiversity, Natural Products and Cancer Treatment

The following sections are included:

• Preface
• Contents
• List of Contributors

Biodiversity describes the universality of all life forms, i.e. plants, animals and microorganisms, and the variety of ecosystems they live in. There are three classes of biodiversity, namely genetic diversity, species diversity and ecosystem diversity. Biodiversity is associated with chemodiversity, which plays a significant role in the discovery and development of drugs and medical pharmacotherapies. In addition to medical applications, biodiversity of microorganisms plays a crucial role in biotechnology and industrial biocatalytic processes. It is expected that in the future, biotechnology will produce high-quality bioproducts, which could replace fossil fuels. In this context, it is important to note that biodiversity is being threatened by the human species. Biodiversity is being destroyed by global environmental changes, such as changes in the atmospheric composition land degradation, depletion of fisheries and shortage of freshwater. Reduced biodiversity may lead to fewer natural chemical substances and hence reduced potential for medical and biotechnological applications.

Metagenomics refers to all the environmental communities and comprises the genomes of hundreds ormore organisms fromall three domains of life i.e. archaea, bacteria and eukarya, as well as those of viruses in contrast to genomics, which comprise the entire genetic complement of only one organism. The study of genetics and genomics from all the environmental communities without prior isolation and cultivation reveals new insights into the biodiversity, evolution and metabolic potential of the uncultured microbial world. By faster sequencing technologies at reasonable costs, sequencing of entire metagenomes enables the discovery of genes and phylogenetic anchors in reconstructed metagenomes of entire communities. Metagenomics can be applied to marine microbes, soil microbials, microbial communities of the human body, etc. Sophisticated bioinformatic tools are necessary to construct and screen metagenomic libraries. Metagenomics comes more and more into focus in pharmaceutical and biotechnological industries for the discovery of novel biocatalysts and antibiotic drugs.

Chemical ecology is an interdisciplinary field that investigates the incidence, function and synthesis of plant-based secondary metabolites. Plant metabolism can be separated into primary and secondary metabolism. Primary metabolism comprises all processes crucial for growth and plant development, while secondary metabolism serves other specific functions. The diversity of secondary metabolites has its origin in the evolution of life itself; these compounds represent adaptations plants have developed to gain a competitive edge in their environment. Pathways for the biosynthesis of secondary metabolites are derived from primary metabolic pathways. Effective chemical defense strategies protect plants e.g. from herbivores, insects or microorganisms, which in turn develop detoxification and adaptation strategies urging the plant to further evolve novel defense systems. This co-evolution leads to reciprocal adaptation. Plants have evolved many different strategies to defend themselves against attackers such as herbivores. These strategies are categorized as direct, indirect, constitutive and induced mechanisms as well as tolerance. The combination of various mechanisms allows plants to efficiently defend themselves against enemies. In particular, the induced indirect defense mechanisms were more thoroughly investigated due to the availability of necessary techniques, for example the determination of up-regulated genes. There was much interest in the correlation and interaction of plants with organisms from higher trophic levels. In this chapter, we discuss plant-plant, plant-fungi, and plant-animal interactions.

Research on marine chemical ecology has provided a great deal of basic information that has advanced the knowledge in the fields of organic chemistry, biochemistry, ecology, behavior, and evolution. The understanding of how chemical signals from the environment, chemical defenses, and other chemical agents intervene in life processes can shed light on the forces driving the ecology and evolution of organisms. So far, several thousand marine natural products have also been chemically defined; many of which are biologically active compounds possessing novel functional groups and molecular structures. Interest in biotechnological applications for marine natural products has increased over the past decade, as the knowledge of the chemistry of marine organisms has developed. Applied studies have identified applications of these compounds as pharmaceuticals. In this chapter, we discuss specific topics of marine chemical ecology such as marine physico-chemical patterns of marine biodiversity, bioactivity and biomedical applications of marine natural products, chemical mediation of interaction among marine organisms, compounds classes, and other topics.

Many microbial products have the potential for therapeutic application, e.g. as anticancer drugs. This chapter presents natural products from terrestrial microbial organisms that attack various targets in tumor cells, e.g. cell cycle inhibitors (inhibitors of phosphoinositide-3-kinase, checkpoint kinase inhibitors, inhibitors of dual specificity phosphatases, inhibitors of cyclin-dependent kinases), inhibitors of histone deacetylases, topoisomerases, or growth factors as well as inhibitors of the proteasome, of heat shock protein 90, nuclear trafficking, or ATPase.

New cancer drugs are most likely be used as part of combination therapy regimens. Attacking different targets in tumor cells may kill tumor cells resistant to one target. The potential of novel target-directed compounds to eradicate otherwise drug-resistant cells is an attractive perspective, which deserves further investigation.

The world's oceans harbour a vast diversity of organisms. During the past decade, interest in marine-derived compounds with potential use in anti-cancer treatment has grown, and investigation of these compounds has intensified. As a result, the number of marine-derived anti-cancer lead compounds that are in clinical or preclinical studies has increased considerably. The coexistence of species in a spatially limited habitat coincides with the evolution of various mechanisms of defense and competition. Sessile species such as algae, corals and sponges are at high risk of predation and in constant competition for suitable attachment space. Consequently, they have developed highly sophisticated chemical defence mechanisms based on the synthesis of toxic secondary metabolites. Marine natural products in clinical trials or on the market as anti-cancer drugs act on a variety of cellular and molecular targets. Some compounds directly inhibit DNA synthesis by interfering with DNA polymerase; others inhibit histone deacetylases (HDACs), which are required for rendering the DNA accessible for transcription. Some compounds hinder tumor metastasis by serving as matrix metalloprotease inhibitors. Other groups of substances interfere with Rho-GTPase function and thereby oppose tumor progression. Another mechanism of anti-tumor activity is the induction of apoptosis or necrosis in cancer cells. The ability to inhibit NF-κB has been attributed to a number of marine natural compounds. This chapter provides an overview on promising marine compounds and their modes of action against tumors.

For the development of novel drugs, it may be helpful to look at traditional medicines because of their time-tested value. All human societies have developed their own medical concepts that are rooted deeply in their “knowledge, skills and practices based on theories, beliefs, and experiences.” (WHO, 2000). Ethnopharmacologists focus particularly on the biological and pharmacological effects of indigenous medicines of past and present cultures. Since plants have been extensively used in traditional medicine since prehistoric times, ethnopharmacology largely deals with ethnobotany and phytotherapy. Using cancer as an example, we give an overview of the impact of ancient European medicine, European medieval cloister medicine, traditional medicine of Native Americans, traditional Chinese medicine, Kampo and Ayurveda for the treatment of this disease.

Throughout Africa, the use of traditional herbal medicines for the treatment of many ailments is well established. Plant extracts and their constituents are being investigated extensively in African research institutes in order to tackle the increasing incidence of cancer in the continent. This chapter highlights some important results of the anti-proliferative potential of plants from Africa as collected in popular science websites such as PubMed, Scopus, Sciencedirect, Scirus, Web-of-knowledge, Scholar Google, etc. It discusses the state-of-art research in Phytotherapy in Africa, with emphasis on most prominent results.

Because of the severe side effects associated with classical anticancer drugs, mainly due to inadequate differentiation between healthy and tumor tissues and the development of drug resistance, there is a need for development of new anticancer drugs and treatment strategies. In this chapter we have introduced several novel plant-based potential anticancer agents that are under investigation or in clinical trials. Themodes of action of plant-derived compounds are manifold and include inhibition of DNA topoisomerase I/II, of nucleotide biosynthesis, of signal transduction pathways, of cyclooxygenase, of prostaglandin to inhibition of cell growth and induction of apoptosis. Furthermore, some natural compounds prevent the development of cancer.

Plants have been used to treat diseases for thousands of years and possess an arsenal of chemotherapeutic agents. Microorganisms and especially some fungi species are also a source of natural compounds used to fight several ailments. Some of these products have already been exploited and are the basis of many anti-cancer drugs. There is continuous search all over the world for naturally occurring antiproliferative compounds. Their mechanisms of action remain a key factor to understand and explain their cytotoxic potential. In this chapter we will discuss the state of discovery of anti-cancer drugs of natural origin, while emphasizing their therapeutic properties.We will also highlight those substances that are currently in the late-stage of discovery and hit compounds acting as tubulin, topoisomerase, heat shock proteins, and cell cycle inhibitors.

The following section is included:

• Index