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      In Vitro Chemopreventive Properties of Green Tea, Rooibos and Honeybush Extracts in Skin Cells

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          Abstract

          The chemopreventive properties of the herbal teas rooibos ( Aspalathus linearis) and honeybush ( Cyclopia spp.) have been demonstrated on mouse skin in vivo but the underlying mechanisms are not clear. The aim of the current study was to determine the anti-proliferative and pro-apoptotic activity of methanol and aqueous extracts of rooibos and two Cyclopia species in different skin cells, using green tea ( Camellia sinensis) as a benchmark. Extracts were also characterised for their major individual polyphenols by high performance liquid chromatography and spectroscopically for the total polyphenol (TP) groups. The methanol extract of rooibos, containing higher levels of polyphenols than its aqueous extract, displayed similar activity to green tea as it selectively targeted premalignant cells by inhibiting cell proliferation at lower concentrations whilst inducing apoptosis via membrane depolarisation at higher concentrations. Specific roles of the major rooibos dihydrochalcones and flavanol/proanthocyanidin-type (FLAVA) compounds are likely to be involved. The aqueous extracts of the Cyclopia species were more active against cell proliferation and at inducing apoptosis which was associated with a higher FLAVA content and a reduced TP/FLAVA ratio. In contrast, their methanol extracts exhibited a cytoprotective effect against apoptosis which was related to their monomeric xanthone and flavanone content. The underlying chemopreventive properties of green tea and the herbal teas appear to be associated with diverse and complex monomeric/polymeric polyphenolic cell interactions.

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          Anti-carcinogenic Effects of the Flavonoid Luteolin

          Luteolin is a flavonoid which is part of our daily nutrition in relatively low amounts (less than 1 mg/day). Nevertheless, some epidemiological studies suggest an inverse correlation between luteolin intake and the risk of some cancer types. Luteolin displays specific anti-inflammatory and anti-carcinogenic effects, which can only partly be explained by its anti-oxidant and free radical scavenging capacities. Luteolin can delay or block the development of cancer cells in vitro and in vivo by protection from carcinogenic stimuli, by inhibition of tumor cell proliferation, by induction of cell cycle arrest and by induction of apoptosis via intrinsic and extrinsic signaling pathways. When compared to other flavonoids, luteolin was usually among the most effective ones, inhibiting tumor cell proliferation with IC50 values between 3 and 50 µM in vitro and in vivo by 5 to 10 mg/kg i.p., intragastric application of 0.1–0.3 mg/kg/d, or as food additive in concentrations of 50 to 200 ppm. Luteolin has been shown to penetrate into human skin, making it also a candidate for the prevention and treatment of skin cancer.
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            Antiproliferative activity of flavonoids on several cancer cell lines.

            Twenty-seven Citrus flavonoids were examined for their antiproliferative activities against several tumor and normal human cell lines. As a result, 7 flavonoids were judged to be active against the tumor cell lines, while they had weak antiproliferative activity against the normal human cell lines. The rank order of potency was luteolin, natsudaidain, quercetin, tangeretin, eriodictyol, nobiletin, and 3,3',4',5,6,7,8-heptamethoxyflavone. The structure-activity relationship established from comparison among these flavones and flavanones showed that the ortho-catechol moiety in ring B and a C2-C3 double bond were important for the antiproliferative activity. As to polymethoxylated flavones, C-3 hydroxyl and C-8 methoxyl groups were essential for high activity.
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              Green Tea Constituent Epigallocatechin-3-Gallate and Induction of Apoptosis and Cell Cycle Arrest in Human Carcinoma Cells

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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                25 November 2016
                December 2016
                : 21
                : 12
                : 1622
                Affiliations
                [1 ]Department of Biochemistry, Stellenbosch University, Private Bag X1, Matieland (Stellenbosch) 7602, South Africa; tmagcwebeba@ 123456sun.ac.za (T.U.M.); pswart@ 123456sun.ac.za (P.S.)
                [2 ]Biostatistics Unit, South African Medical Research Council, P.O. Box 19070, Tygerberg 7505, South Africa; sonja.swanevelder@ 123456mrc.ac.za
                [3 ]Post-Harvest and Wine Technology Division, Agricultural Research Council (Infruitec-Nietvoorbij), Private Bag X5026, Stellenbosch 7599, South Africa; joubertL@ 123456arc.agric.za
                [4 ]Department of Food Science, Stellenbosch University, Private Bag X1, Matieland (Stellenbosch) 7602, South Africa
                [5 ]Institute of Biomedical and Microbial Biotechnology, Cape Peninsula University of Technology, P.O. Box 1906, Bellville 7535, South Africa
                Author notes
                [* ]Correspondence: gelderblomw@ 123456cput.ac.za ; Tel.: +27-21-938-0286
                Article
                molecules-21-01622
                10.3390/molecules21121622
                6273016
                27897996
                79c0e80a-023f-466f-8518-dfd47f6460f2
                © 2016 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
                : 30 October 2016
                : 21 November 2016
                Categories
                Article

                anti proliferative,pro-apoptotic,flavanols,herbal teas,skin cancer

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