Antiproliferative effects of dibenzocyclooctadiene lignans isolated from Schisandra chinensis in human cancer cells

Min, Hye‐Young; Park, Eun-Jung; Hong, Ji‐Young; Kang, You-Jin; Kim, Sun-Jack; Chung, Hwa‐Jin; Woo, Eun‐Rhan; Hung, Tran Manh; Youn, Ui Jung; Kim, Yeong Shik; Kang, Sam Sik; Bae, KiHwan; Lee, Sang Kook

doi:10.1016/j.bmcl.2007.11.082

Cited by 85 publications

(57 citation statements)

References 17 publications

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“…Schizandrin B and C are components of SC extract (Xu et al, 2011). Schizandrin B has been used to treat vascular injury (Chiu et al, 2004;Kim et al, 2011;Park et al, 2012) and schizandrin C has been reported to induce leukemia cell death (Park et al, 2009), and the deaths of human cancer cell lines (Min et al, 2008;Yasukawa et al, 1992). However, the underlying pharmacological mechanisms of SC extract are not clearly understood.…”

Section: Introductionmentioning

confidence: 99%

Schizandra chinensisextracts induce apoptosis in human gastric cancer cells via JNK/p38 MAPK activation and the ROS-mediated/mitochondria-dependent pathway

Kim

Lee

Park

et al. 2014

Pharmaceutical Biology

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Objectives: This study investigates the mechanism of SCE-induced apoptosis in AGS human gastric cancer cells. Materials and methods: SCE concentrations from 100 to 400 mg/ml were used. Cell viabilities were determined using MTT assay. Members of the Bcl-2 family and Bax were detected by Western blotting. RT-PCR was performed to measure the expression level of the Fas/FasL pro-apoptotic genes.Results: SCE inhibited the proliferation AGS cells for 24 or 72 h (inhibition by 3.1% ± 5.2% at 100 mg/ml and 87.3% ± 7.6% at 400 mg/ml at 24 h and by 40.2% ± 5.3% 100 mg/ml and 95.3% ± 1.3% 400 mg/ml at 72 h) and increased the sub-G1 phase (25.3% ± 5.2% at 100 mg/ml and 370.2% ± 7.2% at 400 mg/ml) and the mitochondrial membrane depolarization (11.2% ± 2.1% at 100 mg/ml and 311.5% ± 6.1% at 400 mg/ml). The SCE-induced apoptotic cell death showed the down-regulation of Bcl-2, but up-regulation of Bax. Subsequently, SCE increased the expression level of Fas/FasL, activated caspase-9 and -3, and increased reactive oxygen species generation. Also, JNK II inhibitor or a p38 MAPK inhibitor inhibited SCE-induced cell death. Discussion and conclusion: These results indicate that SCE might be an effective chemotherapeutic for the treatment of human gastric cancer.

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Section: Introductionmentioning

confidence: 99%

Schizandra chinensisextracts induce apoptosis in human gastric cancer cells via JNK/p38 MAPK activation and the ROS-mediated/mitochondria-dependent pathway

Kim

Lee

Park

et al. 2014

Pharmaceutical Biology

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“…Several studies have demonstrated the diverse pharmacological activities of S. chinensis, which include anti-oxidant, anti-tumor, anti-obesity, anti-inflammatory, and cardioprotective effects. [11][12][13][14][15] In addition, hepatoprotective activities of S. chinensis have also been reported. [16][17][18][19] A recent study of ours showed that S. chinensis has a protective effect against ER stress-induced hepatic steatosis (unpublished data).…”

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confidence: 99%

Protective Effect of Gomisin N against Endoplasmic Reticulum Stress-Induced Hepatic Steatosis

Jang

Yun

Kim

et al. 2016

Biological & Pharmaceutical Bulletin

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Gomisin N is a physiological substance derived from Schisandra chinensis. In the present study, the in vitro and in vivo effects of gomisin N on endoplasmic reticulum (ER) stress and hepatic steatosis were investigated. We quantified the expression of markers of ER stress, including glucose regulated protein 78 (GRP78), CCAAT/enhancer binding protein (C/EBP) homolog protein (CHOP), and X-box-binding protein-1 (XBP-1), and triglyceride (TG) accumulation, in HepG2 cells treated with tunicamycin or palmitate. Tunicamycin treatment in HepG2 cells induced expression of markers of ER stress and increased TG levels; Gomisin N reversed these effects, reducing the expression of markers of ER stress and TG levels. Similar effects were seen following palmitate pretreatment of HepG2 cells. The inhibitory effects of gomisin N were further confirmed in mice injected with tunicamycin. Gomisin N reduced expression of markers of ER stress and decreased TG levels in mouse liver after tunicamycin injection. Furthermore, gomisin N decreased expression of inflammatory and lipogenic genes in palmitate-incubated HepG2 cells. These results suggest that gomisin N inhibits ER stress and ameliorates hepatic steatosis induced by ER stress. Key words gomisin N; endoplasmic reticulum (ER) stress; hepatic steatosis; lipogenesis; inflammationThe endoplasmic reticulum (ER) plays critical roles in the synthesis of secreted and membrane proteins by mediating protein folding, production of lipids and sterols, and the storage of intracellular Ca 2+ . 1) However, pathological factors that disrupt ER homeostasis lead to the accumulation of unfolded protein in the ER lumen, provoking ER stress. Cells usually survive early stress by attenuating protein translation, removing unfolded proteins, and upregulating protein chaperons via the unfolded protein response (UPR).1) However, prolonged ER stress can lead to cell death and cause several diseases including ischemia/reperfusion injury, heart disease, and diabetes. [2][3][4][5] Recent studies show that hepatic ER stress is observed in metabolic diseases such as obesity and diabetes.2-5) ER stress contributes to development of insulin resistance and hepatic steatosis in non-alcoholic fatty liver disease (NAFLD). [6][7][8][9]

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“…More than 40 pharmacologically active lignans have been isolated from the fruit of S. chinensis (15)(16)(17)(18)(19)(20). The major lignans in S. chinensis are schisandrin, schisandrin B, schisandrin C, isoschizandrin, deoxyschisandrin, gomisin A, gomisin N and wuweizisu C, and there have been shown to exert a wide array of pharmacological and biological activities including anti-cancer effects (18,(22)(23)(24)(25)(26)31). However, the precise mechanism of schisandrin C-mediated cell growth inhibition is unclear.…”

Section: Discussionmentioning

confidence: 99%

“…The seeds and fruits of S. chinensis are enriched in lignans, and more than 40 lignans have been isolated from this plant (15)(16)(17)(18)(19)(20)(21). Some lignans have previously been reported to induce cell cycle arrest and apoptosis in human cancer cell lines including leukemia cells (22)(23)(24)(25)(26). However, the underlying molecular mechanisms for their putative therapeutic effects are not clear.…”

Section: Introductionmentioning

confidence: 99%

Induction of G1 arrest and apoptosis by schisandrin C isolated from Schizandra chinensis Baill in human leukemia U937 cells

Park

Choi²,

Hyun³

et al. 2009

Int J Mol Med

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Abstract. We isolated two phytochemical lignans, schisandrin and schisandrin C, from Schizandra chinensis Baill and investigated their anti-cancer effects in human leukemia U937 cells. Schisandrin C inhibited cell growth in a dosedependent manner, which was associated with the induction of G1 arrest of the cell cycle and apoptosis; schisandrin did not inhibit growth. Schisandrin C induced G1 arrest was correlated with down-regulation of cyclin D1, cyclin E, cyclindependent kinase (Cdk) 4 and E2Fs expression, inhibition of phosphorylation of retinoblastoma protein (pRB), and upregulation of the Cdk inhibitor p21(WAF1/CIP1). In addition, schisandrin C-induced apoptosis was associated with downregulation of expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, proteolytic activation of caspase-3 and -9, and a concomitant degradation of poly(ADP-ribose) polymerase (PARP). Furthermore, schisandrin C-induced apoptosis was significantly inhibited by a caspase-3 specific inhibitor z-DEVD-fmk, indicating an important role for caspase-3 in the schisandrin C mechanism. In summary, growth inhibition by schisandrin C is related to cell cycle arrest at G1 and induction of caspase-3-dependent apoptosis in U937 cells; these findings suggest that schisandrin C may be a useful chemotherapeutic agent.

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Antiproliferative effects of dibenzocyclooctadiene lignans isolated from Schisandra chinensis in human cancer cells

Cited by 85 publications

References 17 publications

Schizandra chinensisextracts induce apoptosis in human gastric cancer cells via JNK/p38 MAPK activation and the ROS-mediated/mitochondria-dependent pathway

Schizandra chinensisextracts induce apoptosis in human gastric cancer cells via JNK/p38 MAPK activation and the ROS-mediated/mitochondria-dependent pathway

Protective Effect of Gomisin N against Endoplasmic Reticulum Stress-Induced Hepatic Steatosis

Induction of G1 arrest and apoptosis by schisandrin C isolated from Schizandra chinensis Baill in human leukemia U937 cells

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