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      Anti-Cancer Properties of the Naturally Occurring Aphrodisiacs: Icariin and Its Derivatives

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          Abstract

          Epimedium (family Berberidaceae), commonly known as Horny Goat Weed or Yin Yang Huo, is commonly used as a tonic, aphrodisiac, anti-rheumatic and anti-cancer agent in traditional herbal formulations in Asian countries such as China, Japan, and Korea. The major bioactive compounds present within this plant include icariin, icaritin and icariside II. Although it is best known for its aphrodisiac properties, scientific and pharmacological studies suggest it possesses broad therapeutic capabilities, especially for enhancing reproductive function and osteoprotective, neuroprotective, cardioprotective, anti-inflammatory and immunoprotective effects. In recent years, there has been great interest in scientific investigation of the purported anti-cancer properties of icariin and its derivatives. Data from in vitro and in vivo studies suggests these compounds demonstrate anti-cancer activity against a wide range of cancer cells which occurs through various mechanisms such as apoptosis, cell cycle modulation, anti-angiogenesis, anti-metastasis and immunomodulation. Of note, they are efficient at targeting cancer stem cells and drug-resistant cancer cells. These are highly desirable properties to be emulated in the development of novel anti-cancer drugs in combatting the emergence of drug resistance and overcoming the limited efficacy of current standard treatment. This review aims to summarize the anti-cancer mechanisms of icariin and its derivatives with reference to the published literature. The currently utilized applications of icariin and its derivatives in cancer treatment are explored with reference to existing patents. Based on the data compiled, icariin and its derivatives are shown to be compounds with tremendous potential for the development of new anti-cancer drugs.

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          Cancer stem cells and drug resistance: the potential of nanomedicine.

          Properties of the small group of cancer cells called tumor-initiating or cancer stem cells (CSCs) involved in drug resistance, metastasis and relapse of cancers can significantly affect tumor therapy. Importantly, tumor drug resistance seems to be closely related to many intrinsic or acquired properties of CSCs, such as quiescence, specific morphology, DNA repair ability and overexpression of antiapoptotic proteins, drug efflux transporters and detoxifying enzymes. The specific microenvironment (niche) and hypoxic stability provide additional protection against anticancer therapy for CSCs. Thus, CSC-focused therapy is destined to form the core of any effective anticancer strategy. Nanomedicine has great potential in the development of CSC-targeting drugs, controlled drug delivery and release, and the design of novel gene-specific drugs and diagnostic modalities. This review is focused on tumor drug resistance-related properties of CSCs and describes current nanomedicine approaches, which could form the basis of novel combination therapies for eliminating metastatic and CSCs.
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            The role of traditional Chinese herbal medicines in cancer therapy--from TCM theory to mechanistic insights.

            Traditional Chinese medicine-based herbal medicines have gained increasing acceptance worldwide in recent years and are being pursued by pharmaceutical companies as rich resources for drug discovery. For many years, traditional Chinese medicines (TCM) have been applied for the treatment of cancers in China and beyond. Herbal medicines are generally low in cost, plentiful, and show very little toxicity or side effects in clinical practice. However, despite the vast interest and ever-increasing demand, the absence of strong evidence-based research and the lack of standardization of the herbal products are the main obstacles toward the globalization of TCM. In recent years, TCM research has greatly accelerated with the advancement of analytical technologies and methodologies. This review of TCM specifically used in the treatment of cancer is divided into two parts. Part one provides an overview of the philosophy, approaches and progress in TCM-based cancer therapy. Part two summarizes the current understanding of how TCM-derived compounds function as anticancer drugs. Georg Thieme Verlag KG Stuttgart-New York.
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              Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug

              Improvement of quality of life and survival of cancer patients will be greatly enhanced by the development of highly effective drugs to selectively kill malignant cells. Artemisinin and its analogs are naturally occurring antimalarials which have shown potent anticancer activity. In primary cancer cultures and cell lines, their antitumor actions were by inhibiting cancer proliferation, metastasis, and angiogenesis. In xenograft models, exposure to artemisinins substantially reduces tumor volume and progression. However, the rationale for the use of artemisinins in anticancer therapy must be addressed by a greater understanding of the underlying mechanisms involved in their cytotoxic effects. The primary targets for artemisinin and the chemical base for its preferential effects on heterologous tumor cells need yet to be elucidated. The aim of this paper is to provide an overview of the recent advances and new development of this class of drugs as potential anticancer agents.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                29 June 2016
                2016
                : 7
                : 191
                Affiliations
                [1] 1Novel Bacteria and Drug Discovery Research Group, School of Pharmacy, Monash University Malaysia Bandar Sunway, Malaysia
                [2] 2Biomedical Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia Bandar Sunway, Malaysia
                [3] 3Division of Genetic and Molecular Biology, Faculty of Science, Institute of Biological Sciences, University of Malaya Kuala Lumpur, Malaysia
                [4] 4Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao Phayao, Thailand
                [5] 5Pharmaceutical Outcomes Research Center, Faculty of Pharmaceutical Sciences, Naresuan University Phitsanulok, Thailand
                [6] 6Division of Physiology, School of Medical Sciences, University of Phayao Phayao, Thailand
                Author notes

                Edited by: Lyndy Joy McGaw, University of Pretoria, South Africa

                Reviewed by: Fang-Rong Chang, Kaohsiung Medical University, Taiwan; Amit Kumar Tyagi, The University of Texas MD Anderson Cancer Center, USA

                *Correspondence: Learn-Han Lee lee.learn.han@ 123456monash.edu ;

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2016.00191
                4925704
                27445824
                9a52ff5f-642f-43e6-af75-65d9d541a235
                Copyright © 2016 Tan, Chan, Pusparajah, Saokaew, Duangjai, Lee and Goh.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 March 2016
                : 16 June 2016
                Page count
                Figures: 6, Tables: 5, Equations: 0, References: 127, Pages: 18, Words: 13519
                Funding
                Funded by: Ministry of Higher Education, Malaysia 10.13039/501100003093
                Funded by: Universiti Malaya 10.13039/501100004386
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                icariin,icaritin,icariside ii,yin yang huo,anti-cancer,ethnopharmacology

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