Special Issue "Natural Products for Multi-Targeted Cancer Treatment: Where Are We Now?"

Guest Editor
Dr. Carmela Fimognari
Laboratory for Genetic and Molecular Toxicology, Department of Pharmacology, University of Bologna, Italy
Website: http://www.unibo.it/SitoWebDocente/default.htm?UPN=carmela.fimognari@unibo.it
E-Mail:
Interests: 1) antitumour pharmacology: identification of natural agents as potential antitumor drugs and definition of their cellular (analysis of apoptosis/necrosis; cell proliferation; cell-cycle progression; cytodifferentiation) and molecular (level of proteins involved in apoptosis and cell-cycle regulation) mechanism; 2) cellular and genetic toxicology: study of the cellular response after treatment with xenobiotics (cytotoxicity; analysis of DNA and RNA damage; fluorescence in situ hybridization)

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

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• natural agents
• anticancer chemotherapy
• chemotherapy resistance
• genotoxicity
• apoptosis
• necrosis
• cell culture studies
• in vivo studies

Type of Paper: Review
Title: Overcoming Multidrug Resistance in Human Cancer Cells by Natural Compounds
Author: Tomohiro Nabekura
Affiliation: Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan; E-Mail: nabe@nupals.ac.jp
Abstract: A major problem in the treatment of cancer is the occurrence of cellular resistance to cytotoxic drugs. Multidrug resistance is a phenomenon whereby tumors become resistant to structurally unrelated anticancer drugs. Although a number of mechanisms mediate multidrug resistance, the first mediator to be characterized at the molecular level was P-glycoprotein encoded by MDR1, also referred to as ABCB1. P-glycoprotein is the first member of the large ATP-binding cassette (ABC) transporter superfamily of membrane transport proteins. P-glycoprotein and other ABC transporters mediate resistance to various classes of anticancer drugs including vinblastine, daunorubicin, and paclitaxel,by actively extruding the drugs from the cells to lower the intracellular concentrations. Therefore, ABC transporters are promising targets for the reversal of multidrug resistance and a better outcome of cancer chemotherapy. The quest for inhibitors of anticancer drug exporters has uncovered natural compounds including quercetin, (-)-epigallocatechin gallate, curcumin, piperine, capsaicin, gingerol and resveratrol, as promising candidates. In this review, for the future development of a safe and effective inhibitor of ABC transporters to overcome multidrug resistance in human cancer, studies on the effects of natural compounds on ABC transporters are summarized.

Type of Paper: Review
Title: Arsenic in Cancer Treatment: Challenges for Application of Realgar Nanoparticles
Authors: Peter Baláž ¹ and Ján Sedlák ²
Affiliations: ¹ Institute of Geotechnics, Slovak Academy of Sciences, 043 53 Košice, Slovakia
² Cancer Research Institute, Slovak Academy of Sciences, 833 91 Bratislava, Slovakia; E-Mail: exonsedl@savba.sk
Abstract: 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 simultaneous evaluation of DNA sequence based alterations together with copy number gains and losses. The requirement for multitargeting approach is the common theme that emerges from these studies. Therefore, the combination of new targeted biologicals and cytotoxic agents are currently under investigation in multimodal treatment regimens. Similarly, combinational principle is applied in traditional Chinese medicine, as formulae consist of several types of medicinal herbs or minerals, in which one represents the principal component, and others serve as adjuvant ones to assist the effects or facilitate the delivery of the principal component. In Western medicine approximately 60 different arsenic preparations have been developed and used during the pharmacological history. In traditional Chinese medicines different form of mineral arsenicals (orpiment - As2S3, realgar - As4S4, and arsenolite - arsenic trioxide, As2O3) are used and realgar alone is included in 22 oral remedies based on Chinese Pharmacopeia Committee (2005). It is known that significant portion of some forms of mineral arsenicals are poorly absorbed into the body and would be unavailable to cause systemic damage. This review primary focuses on the application of arsenic sulphide (realgar) for treatment of various forms of cancer. Our recent results with nanorealgar use in multiple myeloma cell lines model in vitro are also documented.