Actions of many herbal medicine products for cancer treatment are linked to an altered production of TGF-β in the target cells. An altered TGF-β production in the target cells will have profound effects on the patients. Therefore, it is important that we review the pros and cons of these products on cancer development and progression in terms of TGF-β signaling. It has been well established that TGF-β is growth inhibitory to benign cells or early stages of cancer cells but it is tumor promoting and metastatic for advanced malignancies. Further, many dietary components can alter gene-specific DNA methylation levels in systemic and in target tissues. Since TGF-β signaling in cancer is closely linked to the DNA methylation profiles, we also review the effect of dietary components on DNA methylation. In light of this knowledge, it is important to note that many natural products that can induce TGF-β production in the target cells may be beneficial in preventing cancer development but may be harmful for cancer patients, especially when they harbor advanced stage cancer. A discussion of the effect of herbal natural products on cancer can be divided into three categories. The first category of herbal medicine products will be those related to the induction of cancer as far as TGF-β is concerned. Since TGF-β is growth inhibitory and pro-apoptosis to benign cells, any herbal medication that can induce the production of TGF-β in the target cells will be beneficial to the patients. However, such herbal medicine may not necessarily be beneficial for patients with established and advanced cancer. The second category of herbal products will inhibit TGF-β signaling and will reduce TGF-β mediated growth promotion and metastasis in advanced cancers. For patients with established and advanced cancer, agents that can inhibit the production of TGF-β may also inhibit cancer growth and metastasis. Finally, the third category of herbal products has no impact on TGF-β signaling, such as lycopene.

Almost all tumors harbor a defective negative feedback loop of signaling by transforming growth factor-β (TGF-β). Epigenetic mechanisms of gene regulation, including DNA methylation, are fundamental to normal cellular function and also play a major role in carcinogenesis. Recent evidence demonstrated that TGF-β signaling mediates cancer development and progression. Many key events in TGF-β signaling in cancer included auto-induction of TGF-β1 and increased expression of DNA methyltransferases (DNMTs), suggesting that DNA methylation plays a significant role in cancer development and progression. In this review, we performed an extensive survey of the literature linking TGF-β signaling to DNA methylation in prostate cancer. It appeared that almost all DNA methylated genes detected in prostate cancer are directly or indirectly related to TGF-β signaling. This knowledge has provided a basis for our future directions of prostate cancer research and strategies for prevention and therapy for prostate cancer.

Abstract Background The medicinal leech, Hirudo medicinalis, is an important model system for the study of nervous system structure, function, development, regeneration and repair. It is also a unique species in being presently approved for use in medical procedures, such as clearing of pooled blood following certain surgical procedures. It is a current, and potentially also future, source of medically useful molecular factors, such as anticoagulants and antibacterial peptides, which may have evolved as a result of its parasitizing large mammals, including humans. Despite the broad focus of research on this system, little has been done at the genomic or transcriptomic levels and there is a paucity of openly available sequence data. To begin to address this problem, we constructed whole embryo and adult central nervous system (CNS) EST libraries and created a clustered sequence database of the Hirudo transcriptome that is available to the scientific community. Results A total of ~133,000 EST clones from two directionally-cloned cDNA libraries, one constructed from mRNA derived from whole embryos at several developmental stages and the other from adult CNS cords, were sequenced in one or both directions by three different groups: Genoscope (French National Sequencing Center), the University of Iowa Sequencing Facility and the DOE Joint Genome Institute. These were assembled using the phrap software package into 31,232 unique contigs and singletons, with an average length of 827 nt. The assembled transcripts were then translated in all six frames and compared to proteins in NCBI's non-redundant (NR) and to the Gene Ontology (GO) protein sequence databases, resulting in 15,565 matches to 11,236 proteins in NR and 13,935 matches to 8,073 proteins in GO. Searching the database for transcripts of genes homologous to those thought to be involved in the innate immune responses of vertebrates and other invertebrates yielded a set of nearly one hundred evolutionarily conserved sequences, representing all known pathways involved in these important functions. Conclusions The sequences obtained for Hirudo transcripts represent the first major database of genes expressed in this important model system. Comparison of translated open reading frames (ORFs) with the other openly available leech datasets, the genome and transcriptome of Helobdella robusta, shows an average identity at the amino acid level of 58% in matched sequences. Interestingly, comparison with other available Lophotrochozoans shows similar high levels of amino acid identity, where sequences match, for example, 64% with Capitella capitata (a polychaete) and 56% with Aplysia californica (a mollusk), as well as 58% with Schistosoma mansoni (a platyhelminth). Phylogenetic comparisons of putative Hirudo innate immune response genes present within the Hirudo transcriptome database herein described show a strong resemblance to the corresponding mammalian genes, indicating that this important physiological response may have older origins than what has been previously proposed.

Background

Blood feeding evolved independently in worms, arthropods and mammals. Among the adaptations to this peculiar diet, these animals developed an armament of salivary molecules that disarm their host's anti-bleeding defenses (hemostasis), inflammatory and immune reactions. Recent sialotranscriptome analyses (from the Greek sialo = saliva) of blood feeding insects and ticks have revealed that the saliva contains hundreds of polypeptides, many unique to their genus or family. Adult tsetse flies feed exclusively on vertebrate blood and are important vectors of human and animal diseases. Thus far, only limited information exists regarding the Glossina sialome, or any other fly belonging to the Hippoboscidae.

Results

As part of the effort to sequence the genome of Glossina morsitans morsitans, several organ specific, high quality normalized cDNA libraries have been constructed, from which over 20,000 ESTs from an adult salivary gland library were sequenced. These ESTs have been assembled using previously described ESTs from the fat body and midgut libraries of the same fly, thus totaling 62,251 ESTs, which have been assembled into 16,743 clusters (8,506 of which had one or more EST from the salivary gland library). Coding sequences were obtained for 2,509 novel proteins, 1,792 of which had at least one EST expressed in the salivary glands. Despite library normalization, 59 transcripts were overrepresented in the salivary library indicating high levels of expression. This work presents a detailed analysis of the salivary protein families identified. Protein expression was confirmed by 2D gel electrophoresis, enzymatic digestion and mass spectrometry. Concurrently, an initial attempt to determine the immunogenic properties of selected salivary proteins was undertaken.

Conclusions

The sialome of G. m. morsitans contains over 250 proteins that are possibly associated with blood feeding. This set includes alleles of previously described gene products, reveals new evidence that several salivary proteins are multigenic and identifies at least seven new polypeptide families unique to Glossina. Most of these proteins have no known function and thus, provide a discovery platform for the identification of novel pharmacologically active compounds, innovative vector-based vaccine targets, and immunological markers of vector exposure.