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      Marine Carotenoid Fucoxanthin Possesses Anti-Metastasis Activity: Molecular Evidence

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          Abstract

          Fucoxanthin is commonly found in marine organisms; however, to date, it has been one of the scarcely explored natural compounds. We investigated its activities in human cancer cell culture-based viability, migration, and molecular assays, and found that it possesses strong anticancer and anti-metastatic activities that work irrespective of the p53 status of cancer cells. In our experiments, fucoxanthin caused the transcriptional suppression of mortalin. Cell phenotype-driven molecular analyses on control and treated cells demonstrated that fucoxanthin caused a decrease in hallmark proteins associated with cell proliferation, survival, and the metastatic spread of cancer cells at doses that were relatively safe to the normal cells. The data suggested that the cancer therapy regimen may benefit from the recruitment of fucoxanthin; hence, it warrants further attention for basic mechanistic studies as well as drug development.

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          Most cited references37

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          Emerging roles of p53 and other tumour-suppressor genes in immune regulation.

          Tumour-suppressor genes are indispensable for the maintenance of genomic integrity. Recently, several of these genes, including those encoding p53, PTEN, RB1 and ARF, have been implicated in immune responses and inflammatory diseases. In particular, the p53 tumour- suppressor pathway is involved in crucial aspects of tumour immunology and in homeostatic regulation of immune responses. Other studies have identified roles for p53 in various cellular processes, including metabolism and stem cell maintenance. Here, we discuss the emerging roles of p53 and other tumour-suppressor genes in tumour immunology, as well as in additional immunological settings, such as virus infection. This relatively unexplored area could yield important insights into the homeostatic control of immune cells in health and disease and facilitate the development of more effective immunotherapies. Consequently, tumour-suppressor genes are emerging as potential guardians of immune integrity.
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            Fucoxanthin induces apoptosis and enhances the antiproliferative effect of the PPARgamma ligand, troglitazone, on colon cancer cells.

            The effect of fucoxanthin, from the edible seaweed Undaria pinnatifida on viability of colon cancer cells and induction of apoptosis was investigated. Fucoxanthin remarkably reduced the viability of human colon cancer cell lines, Caco-2, HT-29 and DLD-1. Furthermore, treatment with fucoxanthin induced DNA fragmentation, indicating apoptosis. The DNA fragmentation in Caco-2 cells treated with 22.6 microM fucoxanthin for 24 h was 10-fold higher than in the control. Fucoxanthin suppressed the level of Bcl-2 protein. Also, DNA fragmentation induced by fucoxanthin was partially inhibited by a caspase inhibitor Z-VAD-fmk. Moreover, combined treatment with 3.8 microM fucoxanthin and 10 microM troglitazone, which is a specific ligand for peroxisome proliferator-activated receptor (PPAR) gamma, effectively decreased the viability of Caco-2 cells. However, separate treatments with these same concentrations of fucoxanthin nor troglitazone did not affect cell viability. These findings indicate that fucoxanthin may act as a chemopreventive and/or chemotherapeutic carotenoid in colon cancer cells by modulating cell viability in combination with troglitazone.
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              Fucoxanthin induces apoptosis in human leukemia HL-60 cells through a ROS-mediated Bcl-xL pathway.

              Fucoxanthin, a natural biologically active substance isolated from Ishige okamurae, evidences antitumor activity in human leukemia cell HL-60 cells via the induction of apoptosis. However, the mechanism underlying fucoxanthin-induced apoptosis in HL-60 cells remains unclear. In this study, we focused on the effect of fucoxanthin induction on the accumulation of reactive oxygen species (ROS), and on the triggering of Bcl-xL signaling pathway in HL-60 cells. We determined that ROS are generated during fucoxanthin-induced cytotoxicity and apoptosis in HL-60 cells, and that N-acetylcysteine (NAC), a ROS scavenger, suppressed fucoxanthin-induced cytotoxicity and apoptosis. Moreover, fucoxanthin-induced the cleavage of caspases -3 and -7, and poly-ADP-ribose polymerase (PARP) and a decrease of Bcl-xL levels, whereas NAC pre-treatment significantly inhibited caspase-3, -7, and PARP cleavage and the reduction in Bcl-xL levels. In this study, it was demonstrated for the first time that fucoxanthin generated ROS and that the accumulation of ROS performed a crucial role in the fucoxanthin-induced Bcl-xL signaling pathway. Copyright 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Mar Drugs
                Mar Drugs
                marinedrugs
                Marine Drugs
                MDPI
                1660-3397
                05 June 2019
                June 2019
                : 17
                : 6
                : 338
                Affiliations
                [1 ]DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba 305-8565, Japan; sukantgarg@ 123456gmail.com (S.G.); sajal.afzal@ 123456aist.go.jp (S.A.); ahmed.elwakeel@ 123456aist.go.jp (A.E.); sharmadamini823@ 123456gmail.com (D.S.); jaspreetk.dhanjal@ 123456aist.go.jp (J.K.D.)
                [2 ]School of Integrative & Global Majors, University of Tsukuba, Tsukuba 305-8577, Japan
                [3 ]DAILAB, Department of Biochemical Engineering & Biotechnology, Indian Institute of Technology (IIT) Delhi, Hauz Khas, New Delhi 110-016, India; navaneethanbio@ 123456gmail.com (N.R.); sundar@ 123456dbeb.iitd.ac.in (D.S.)
                Author notes
                [* ]Correspondence: s-kaul@ 123456aist.go.jp (S.C.K.); renu-wadhwa@ 123456aist.go.jp (R.W.); Tel.: +81-29-861-6713 (S.C.K.); +81-29-861-9464 (R.W.)
                Author information
                https://orcid.org/0000-0003-1645-4827
                Article
                marinedrugs-17-00338
                10.3390/md17060338
                6627158
                31195739
                4e343064-3524-4c6a-9e8e-422b5943546d
                © 2019 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
                : 15 May 2019
                : 31 May 2019
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                fucoxanthin,cancer,p53–mortalin interaction,abrogation,growth arrest,therapy

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