http://www.mdpi.com/journal/toxins/special_issues/prod-cancer-treatment/ Dear Colleagues, Cancer is a biomedically complex group of diseases involving cell transformation, dysregulation of apoptosis, proliferation, invasion, angiogenesis and metastasis. Because of the enormous biological diversity of cancer, therapies that have been targeted to a single signaling molecule have shown limited promise. Rather, strategic combination of agents targeted against the most critical of those alterations will be needed. Another approach is the use of more unspecific agents that inhibit or modulate several relevant targets simultaneously. Accumulating evidence suggests that natural products interact with numerous latest targets. This supports the notion that they influence numerous biochemical and molecular cascades and could represent a more realistic approach to the actuality of carcinogenesis and the increasing problem of emerging resistance to monofunctional agents. A great deal of information is now available showing that several natural agents are endowed with potent anticancer activity. The affordability of natural products provides additional window of opportunities, such as their association with traditional anticancer drugs for overcoming cancer cell resistance to chemotherapy. In spite of all these advantages, several questions concerning the role of natural agents in the treatment of cancer remain unanswered. One of these questions is that of the optimal treatment dose needed to maximize positive and minimize the undesired adverse effects reported in cell culture and in vivo models. Some natural compounds have been shown to induce both dose-dependent pro-oxidative and anti-oxidative effects, genotoxicity and antigenotoxicity, apoptosis-inducing effects and necrosis. Further systematic study of natural compounds is needed to define the transferability of in vitro to in vivo and ultimately to human studies. Controlled intervention trials should be performed to prove their efficacy in humans. Carmela Fimognari, Ph.D. Guest Editor Submission All papers should be submitted to toxins@mdpi.com with copy to the guest editor. To be published continuously until the deadline and papers will be listed together at the special websites. Submitted papers should not have been previously published nor be currently under consideration for publication elsewhere. All papers are refereed through a peer review process. A guide for authors, sample copies and other relevant information for submitting papers are available on the Instructions for Authors page. Toxins is an international peer-reviewed monthly journal published by MDPI. Article Processing Charges (APC) for publication in this open access journal are waived for well-prepared manuscripts submitted by 30 June 2010. English correction or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those paper accepted for publication, that require extensive additional formatting and/or English corrections. http://www.mdpi.com/2072-6651/2/6/1568/ While intensive efforts have been made for the treatment of cancer, this disease is still the second leading cause of death in many countries. Metastatic breast cancer, late-stage colon cancer, malignant melanoma, multiple myeloma, and other forms of cancer are still essentially incurable in most cases. Recent advances in genomic technologies have permitted the simultaneous evaluation of DNA sequence-based alterations together with copy number gains and losses. The requirement for a multi-targeting approach is the common theme that emerges from these studies. Therefore, the combination of new targeted biological and cytotoxic agents is currently under investigation in multimodal treatment regimens. Similarly, a combinational principle is applied in traditional Chinese medicine, as formulas consist of several types of medicinal herbs or minerals, in which one represents the principal component, and the others serve as adjuvant ones that assist the effects, or facilitate the delivery, of the principal component. In Western medicine, approximately 60 different arsenic preparations have been developed and used in pharmacological history. In traditional Chinese medicines, different forms of mineral arsenicals (orpiment—As2S3, realgar—As4S4, and arsenolite—arsenic trioxide, As2O3) are used, and realgar alone is included in 22 oral remedies that are recognized by the Chinese Pharmacopeia Committee (2005). It is known that a significant portion of some forms of mineral arsenicals is poorly absorbed into the body, and would be unavailable to cause systemic damage. This review primary focuses on the application of arsenic sulfide (realgar) for treatment of various forms of cancer in vitro and in vivo. http://www.mdpi.com/2072-6651/2/6/1568/ Mon, 21 Jun 2010 00:00:00 CEST Toxins 2010-06-21 2 6 Review 1568 1581 2072-6651 Arsenic in Cancer Treatment: Challenges for Application of Realgar Nanoparticles (A Minireview) 2010-06-21 doi: 10.3390/toxins2061568 Baláž Sedlák http://www.mdpi.com/2072-6651/2/6/1207/ Multidrug resistance is a phenomenon whereby tumors become resistant to structurally unrelated anticancer drugs. P-glycoprotein belongs to the large ATP-binding cassette (ABC) transporter superfamily of membrane transport proteins. P-glycoprotein mediates resistance to various classes of anticancer drugs including vinblastine, daunorubicin, and paclitaxel, by actively extruding the drugs from the cells. The quest for inhibitors of anticancer drug efflux transporters has uncovered natural compounds, including (-)-epigallocatechin gallate, curcumin, capsaicin, and guggulsterone, as promising candidates. In this review, studies on the effects of natural compounds on P-glycoprotein and anticancer drug efflux transporters are summarized. http://www.mdpi.com/2072-6651/2/6/1207/ Fri, 28 May 2010 00:00:00 CEST Toxins 2010-05-28 2 6 Review 1207 1224 2072-6651 Overcoming Multidrug Resistance in Human Cancer Cells by Natural Compounds 2010-05-28 doi: 10.3390/toxins2061207 Nabekura http://www.mdpi.com/2072-6651/2/4/517/ A voluminous literature suggests that an increase in consumption of fruit and vegetables is a relatively easy and practical strategy to reduce significantly the incidence of cancer. The beneficial effect is mostly associated with the presence of phytochemicals in the diet. This review focuses on a group of them, namely isothiocyanate, curcumin, genistein, epigallocatechin gallate, lycopene and resveratrol, largely studied as chemopreventive agents and with potential clinical applications. Cellular and animal studies suggest that these molecules induce apoptosis and arrest cell growth by pleiotropic mechanisms. The anticancer efficacy of these compounds may result from their use in monotherapy or in association with chemotherapeutic drugs. This latter approach may represent a new pharmacological strategy against several types of cancers. However, despite the promising results from experimental studies, only a limited number of clinical trials are ongoing to assess the therapeutic efficacy of these molecules. Nevertheless, the preliminary results are promising and raise solid foundations for future investigations. http://www.mdpi.com/2072-6651/2/4/517/ Wed, 31 Mar 2010 00:00:00 CEST Toxins 2010-03-31 2 4 Review 517 551 2072-6651 Phytochemicals in Cancer Prevention and Therapy: Truth or Dare? 2010-03-31 doi: 10.3390/toxins2040517 Russo Spagnuolo Tedesco Russo http://www.mdpi.com/2072-6651/2/1/128/ As cancer is a multifactor disease, it may require treatment with compounds able to target multiple intracellular components. We summarize here how curcumin is able to modulate many components of intracellular signaling pathways implicated in inflammation, cell proliferation and invasion and to induce genetic modulations eventually leading to tumor cell death. Clinical applications of this natural compound were initially limited by its low solubility and bioavailability in both plasma and tissues but combination with adjuvant and delivery vehicles was reported to largely improve bio-availability of curcumin. Moreover, curcumin was reported to act in synergism with several natural compounds or synthetic agents commonly used in chemotherapy. Based on this, curcumin could thus be considered as a good candidate for cancer prevention and treatment when used alone or in combination with other conventional treatments. http://www.mdpi.com/2072-6651/2/1/128/ Thu, 21 Jan 2010 00:00:00 CET Toxins 2010-01-21 2 1 Review 128 162 2072-6651 Curcumin―The Paradigm of a Multi-Target Natural Compound with Applications in Cancer Prevention and Treatment 2010-01-21 doi: 10.3390/toxins2010128 Marie-Hélène Teiten Serge Eifes Mario Dicato Marc Diederich