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      The Application of Embelin for Cancer Prevention and Therapy †

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          Abstract

          Embelin is a naturally-occurring benzoquinone compound that has been shown to possess many biological properties relevant to human cancer prevention and treatment, and increasing evidence indicates that embelin may modulate various characteristic hallmarks of tumor cells. This review summarizes the information related to the various oncogenic pathways that mediate embelin-induced cell death in multiple cancer cells. The mechanisms of the action of embelin are numerous, and most of them induce apoptotic cell death that may be intrinsic or extrinsic, and modulate the NF-κB, p53, PI3K/AKT, and STAT3 signaling pathways. Embelin also induces autophagy in cancer cells; however, these autophagic cell-death mechanisms of embelin have been less reported than the apoptotic ones. Recently, several autophagy-inducing agents have been used in the treatment of different human cancers, although they require further exploration before being transferred from the bench to the clinic. Therefore, embelin could be used as a potential agent for cancer therapy.

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          Most cited references105

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          Role for Rab7 in maturation of late autophagic vacuoles.

          The small GTP binding protein Rab7 has a role in the late endocytic pathway and lysosome biogenesis. The role of mammalian Rab7 in autophagy is, however, unknown. We have addressed this by inhibiting Rab7 function with RNA interference and overexpression of dominant negative Rab7. We show here that Rab7 was needed for the formation of preferably perinuclear, large aggregates, where the autophagosome marker LC3 colocalised with Rab7 and late endosomal and lysosomal markers. By electron microscopy we showed that these large aggregates corresponded to autophagic vacuoles surrounding late endosomal or lysosomal vesicles. Our experiments with quantitative electron microscopy showed that Rab7 was not needed for the initial maturation of early autophagosomes to late autophagic vacuoles, but that it participated in the final maturation of late autophagic vacuoles. Finally, we showed that the recruitment of Rab7 to autophagic vacuoles was retarded in cells deficient in the lysosomal membrane proteins Lamp1 and Lamp2, which we have recently shown to accumulate late autophagic vacuoles during starvation. In conclusion, our results showed a role for Rab7 in the final maturation of late autophagic vacuoles.
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            Targeting the STAT3 signaling pathway in cancer: role of synthetic and natural inhibitors.

            Signal transducers and activators of transcription (STATs) comprise a family of cytoplasmic transcription factors that mediate intracellular signaling that is usually generated at cell surface receptors and thereby transmit it to the nucleus. Numerous studies have demonstrated constitutive activation of STAT3 in a wide variety of human tumors, including hematological malignancies (leukemias, lymphomas, and multiple myeloma) as well as diverse solid tumors (such as head and neck, breast, lung, gastric, hepatocellular, colorectal and prostate cancers). There is strong evidence to suggest that aberrant STAT3 signaling promotes initiation and progression of human cancers by either inhibiting apoptosis or inducing cell proliferation, angiogenesis, invasion, and metastasis. Suppression of STAT3 activation results in the induction of apoptosis in tumor cells, and accordingly its pharmacological modulation by tyrosine kinase inhibitors, antisense oligonucleotides, decoy nucleotides, dominant negative proteins, RNA interference and chemopreventive agents have been employed to suppress the proliferation of various human cancer cells in culture and tumorigenicity in vivo. However, the identification and development of novel drugs that can target deregulated STAT3 activation effectively remains an important scientific and clinical challenge. This review presents the evidence for critical roles of STAT3 in oncogenesis and discusses the potential for development of novel cancer therapies based on mechanistic understanding of STAT3 signaling cascade. Copyright © 2013 Elsevier B.V. All rights reserved.
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              Promoting apoptosis as a strategy for cancer drug discovery.

              Apoptosis is deregulated in many cancers, making it difficult to kill tumours. Drugs that restore the normal apoptotic pathways have the potential for effectively treating cancers that depend on aberrations of the apoptotic pathway to stay alive. Apoptosis targets that are currently being explored for cancer drug discovery include the tumour-necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptors, the BCL2 family of anti-apoptotic proteins, inhibitor of apoptosis (IAP) proteins and MDM2.
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
                MDPI
                1420-3049
                09 March 2018
                March 2018
                : 23
                : 3
                : 621
                Affiliations
                [1 ]College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea; gokjh1647@ 123456gmail.com (J.-H.K.); seokgeun@ 123456khu.ac.kr (S.-G.L.); wmyang@ 123456khu.ac.kr (W.M.Y.); jyum@ 123456khu.ac.kr (J.-Y.U.)
                [2 ]Department for Management of Science and Technology Development, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam
                [3 ]Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam
                [4 ]Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; srishti.mishra@ 123456u.nus.edu (S.M.); phcsmk@ 123456nus.edu.sg (M.K.S.)
                Author notes
                [†]

                Running Title: Potential Antineoplastic Effects of Embelin

                Author information
                https://orcid.org/0000-0002-0060-5777
                https://orcid.org/0000-0002-2882-0612
                Article
                molecules-23-00621
                10.3390/molecules23030621
                6017120
                29522451
                3e96bea0-b677-400c-bb02-4600c4439104
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 12 February 2018
                : 08 March 2018
                Categories
                Review

                embelin,apoptosis,autophagy,cancer,cell signaling
                embelin, apoptosis, autophagy, cancer, cell signaling

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