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      • Induction of apoptosis by Moutan Cortex Radicis in human gastric cancer cells through the activation of caspases and the AMPK signaling pathway

        Park, C.,Han, M.H.,Park, S.H.,Hong, S.H.,Kim, G.Y.,Moon, S.K.,Kim, W.J.,Choi, Y.H. Sociedade Brasileira de Farmacognosia 2017 Revista brasileira de farmacognosia Vol.27 No.3

        <P>Moutan Cortex Radicis, the root bark of Paeonia x suffruticosa Andrews, Paeoniaceae, has been widely used in traditional medicine therapy. Although it has been shown to possess many pharmacological activities, the molecular mechanisms of its anti-cancer activity have not been clearly elucidated. In the present study, we investigated the pro-apoptotic effects of the ethanol extract of Moutan Cortex Radicis in human gastric cancer AGS cells. Moutan Cortex Radicis treatment inhibited the cell viability of AGS cells in a concentration-dependent manner, which was associated with apoptotic cell death. Moutan Cortex Radicis's induction of apoptosis was connected with the upregulation of death receptor 4, death receptor 5, tumor necrosis factor-related apoptosis-inducing ligand, Fas ligand, and Bax, and the downregulation of Bcl-2 and Bid. Moutan Cortex Radicis treatment also induced the loss of mitochondrial membrane potential (Delta psi m), the proteolytic activation of caspases (-3, -8, and -9), and the degradation of poly(ADPribose) polymerase, an activated caspase-3 substrate protein. However, the pre-treatment of a caspase-3 inhibitor significantly attenuated Moutan Cortex Radicis-induced apoptosis and cell viability reduction. In addition, Moutan Cortex Radicis treatment effectively activated the adenosine monophosphate-activated protein kinase signaling pathway; however, a specific inhibitor of AMPK significantly reduced Moutan Cortex Radicis-induced apoptosis. Overall, the results suggest that the apoptotic activity of Moutan Cortex Radicis may be associated with a caspase-dependent cascade through the activation of both extrinsic and intrinsic signaling pathways connected with adenosine monophosphate-activated protein kinase activation, and Moutan Cortex Radicis as an activator of adenosine monophosphate-activated protein kinase could be a prospective application to treat human cancers. (C) 2016 Sociedade Brasileira de Farmacognosia. Published by Elsevier Editora Ltda.</P>

      • Ethanol extract of Prunus mume fruit attenuates hydrogen peroxide-induced oxidative stress and apoptosis involving Nrf2/HO-1 activation in C2C12 myoblasts

        Kang, J.S.,Kim, D.J.,Kim, G.Y.,Cha, H.J.,Kim, S.,Kim, H.S.,Park, C.,Hwang, H.J.,Kim, B.W.,Kim, C.M.,Choi, Y.H. Sociedade Brasileira de Farmacognosia 2016 Revista brasileira de farmacognosia Vol.26 No.2

        <P>The fruit of the Prunus mume (Siebold) Siebold & Zucc., Rosaceae (Korean name: Maesil) has long been used as a health food or valuable medicinal material in traditional herb medicine in Southeast Asian countries. In this study, we determined the potential therapeutic efficacy of the ethanol extract of P. mume fruits (EEPM) against H2O2-induced oxidative stress and apoptosis in the murine skeletal muscle myoblast cell line C2C12, and sought to understand the associated molecular mechanisms. The results indicated that exposure of C2C12 cells to H2O2 caused a reduction in cell viability by increasing the generation of intracellular reactive oxygen species and by disrupting mitochondrial membrane permeability, leading to DNA damage and apoptosis. However, pretreatment of the cells with EEPM before H2O2 exposure effectively attenuated these changes, suggesting that EEPM prevented H2O2-induced mitochondria-dependent apoptosis. Furthermore, the increased ex-pression and phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2) and up-regulation of heme oxygenase-1 (HO-1), a phase II antioxidant enzyme, were detected in EEPM-treated C2C12 cells. We also found that zinc protoporphyrin IX, an HO-1 inhibitor, attenuated the protective effects of EEPM against H2O2-induced reactive oxygen species accumulation and cytotoxicity. Therefore, these results indicate that the activation of the Nrf2/HO-1 pathway might be involved in the protection of EEPM against H2O2-induced cellular oxidative damage. In conclusion, these results show that EEPM contributes to the prevention of oxidative damage and could be used as a nutritional agent for oxidative stress-related diseases. (C) 2016 Sociedade Brasileira de Farmacognosia. Published by Elsevier Editora Ltda. All rights reserved.</P>

      • Antiproliferative effect of Momordica cochinchinensis seeds on human lung cancer cells and isolation of the major constituents

        Yu, J.S.,Roh, H.S.,Lee, S.,Jung, K.,Baek, K.H.,Kim, K.H. Sociedade Brasileira de Farmacognosia 2017 Revista brasileira de farmacognosia Vol.27 No.3

        <P>Gac, Momordica cochinchinensis (Lour.) Spreng., Cucurbitaceae, is an indigenous South Asian edible fruit and has been used therapeutically in Traditional Chinese Medicine. Previous studies have shown that M. cochinchinensis seed (Momordicae Semen) has various pharmaceutical properties such as antioxidant and anti-ulcer effects as well as contains secondary metabolites with potential anticancer activities such as triterpenoids and saponins. However, its biological activities in cancer have not yet been investigated. In this study, we found that its ethanol extract reduced cell proliferation in four human lung cancer cell lines, A549, H1264, H1299 and Calu-6. Phytochemical investigation of the ethanol extract was carried out, and resulted in isolation of two major saponins, which were identified as gypsogenin 3-O-beta-D-galactopyranosyl(1 -> 2)-[alpha-L-rhamnopyranosyl(1 -> 3)]-beta-D-glucuronopyranoside (1) and quillaic acid 3-O-beta-D-galactopyranosyl(1 -> 2)-[alpha-L-rhamnopyranosyl(1 -> 3)]-beta-D-glucuronopyranoside (2). Treatment with these isolated compounds (1 and 2) decreased cell proliferation in all human lung cancer cell lines tested. In addition, the compounds attenuated primary lung endothelial cell proliferation. Taken together, these findings suggest M. cochinchinensis seeds have antiproliferative activity on human lung cancer cells as well as angiostatic effect on lung endothelial cells. (C) 2017 Sociedade Brasileira de Farmacognosia. Published by Elsevier Editora Ltda.</P>

      • Fucoidan induces G1 arrest of the cell cycle in EJ human bladder cancer cells through down-regulation of pRB phosphorylation

        Park, H.Y.,Choi, I.W.,Kim, G.Y.,Kim, B.W.,Kim, W.J.,Choi, Y.H. Sociedade Brasileira de Farmacognosia 2015 Revista brasileira de farmacognosia Vol.25 No.3

        Fucoidan, a sulfated polysaccharide found in marine algae and brown seaweeds, has been shown to inhibit the in vitro growth of human cancer cells. This study was conducted in cultured human bladder cancer EJ cells to elucidate the possible mechanisms by which fucoidan exerts its anti-proliferative activity, which until now has remained poorly understood. Fucoidan treatment of EJ cells resulted in dose-dependent inhibition of cell growth and induced apoptotic cell death. Flow cytometric analysis revealed that fucoidan led to G1 arrest in cell cycle progression. It was associated with down-regulation of cyclin D1, cyclin E, and cyclin-dependent-kinases (Cdks) in a concentration-dependent manner, without any change in Cdk inhibitors, such as p21 and p27. Furthermore, dephosphorylation of retinoblastoma protein (pRB) by this compound was associated with enhanced binding of pRB with the transcription factors E2F-1 and E2F-4. Overall, our results demonstrate that fucoidan possesses anticancer activity potential against bladder cancer cells by inhibiting pRB phosphorylation.

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