• Journal of Life Science
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• v.30 no.4
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• pp.379-385
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• 2020

Phlojodicarpus sibiricus and Artemisia kruhsiana Besser are medicinal plants traditionally used in Russia. Phlojodicarpus sibiricus extracts (PSE) have been shown to have anti-obesity properties, and Artemisia kruhsiana Besser extracts (AKBE) contain terpenoid compounds that exert various medicinal effects. Here, we investigated the potential pro-apoptotic effects of PSE and AKBE in diffuse large B-cell lymphoma (DLBCL) and elucidated the underlying mechanism. PSE and AKBE treatment of six DLBCL cell lines with various genetic abnormalities effectively reduced cell viability in a dose-dependent manner, while having a minimal impact on the survival of normal murine bone marrow cells and splenocytes. This suggests that the cytotoxic effects of PSE and AKBE are specific to DLBCL cells. Therefore, we expect limited side effects when these plant extracts are administered to DLBCL patients. Our JC-1 assays demonstrate that the pro-apoptotic effects of these plant extracts are produced by a reduction of anti-apoptotic Bcl-2 family members and, thereby, disruption of the mitochondrial membrane potential. Moreover, PSE and AKBE induce cell death independently of Myc, whose abnormalities are frequently observed in patients with DLBCL and are associated with poor prognosis. Our findings reveal hitherto uncharacterized pro-apoptotic effects of PSE and AKBE in DLBCL. Isolation of single compounds with anti-lymphoma activities should be pursued further.

• The Journal of Korean Medicine
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• v.27 no.4
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• pp.84-95
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• 2006

Costunolide is an active sesquiterpene lactone isolated from the root of Saussurea lappa Clarke and is known to exhibit a variety of biological activities, including anti-carcinogenic and anti-inflammatory effects. Nevertheless, the pharmacological pathways of costunolide have not yet been fully elucidated. In this study, its cytotoxic effects were examined using AGS gastric cancer cells. Its treatment resulted in apoptosis in a dose- and time-dependent manner. The effects were attributed to the regulation of pro-apoptotic molecules and suppression of anti-apoptotic molecules. These results suggest that costunolide may be a candidate to deal with gastric cancers by chemopreventive agents.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.95.1-95.1
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• 2003

Sopungsungi-won has been used as a traditional medicine for diabetes and it has been proved evidently as a potential remedy for type 2 diabetes mellitus. Both in vivo and in vitro experiments with water extract of Sopungsungi-won have been reported to exhibit anti-diabetic effects in our previous studies. In the present study, we have chosen Rheum undulatum (RU), which is the main component of Sopungsungi-won, to examine its anti-apoptotic effect on pancreatic b-cells, HIT-T15, against oxidative stress induced by hydrogen peroxide (H$_2$O$_2$). (omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.256.1-256.1
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• 2002

We investigated the anti-proliferative effects of a new compound. ircinin-1. from the sponge Sarcotragus sp. on SK-MEL -2 human skin cancer cells. From the data of MTT assay, cell viability was decreased by ircinin-1 in a dose-dependent manner. We observed that the anti-proliferative effect of ircinin-1 was due to the induction of apoptosis, which was confirmed by observing the morphological changes. the increased ratio of pro-apoptotic protein Bax to anti-apoptotic protein Bcl-2, and cleavage of poly(ADP-ribose) polymerase protein, via activation of caspase-3. (omitted)

• BMB Reports
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• v.44 no.4
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• pp.267-272
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• 2011

ZAS3 is a large zinc finger transcription repressor that binds the ${\kappa}B$-motif via two signature domains of ZASN and ZASC. A loss-of-function study showed that lack of ZAS3 protein induced accelerated cell proliferation and tumorigenesis. Conversely, gain-of-function studies showed that ZAS3 repressed $NF{\kappa}B$-activated transcription by competing with $NF{\kappa}B$ for the ${\kappa}B$-motif. Based on these observations, we hypothesize that ZAS3 promotes apoptosis by interrupting anti-apoptotic activity of $NF{\kappa}B$. Here, we present evidence that upon $TNF{\alpha}$ stimulation, ZAS3 inhibits $NF{\kappa}B$-mediated cell survival and promotes caspase-mediated apoptosis. The inhibitory effect of ZAS3 on $NF{\kappa}B$ activity is mediated by neither direct association with $NF{\kappa}B$ nor disrupting nuclear localization of $NF{\kappa}B$. Instead, ZAS3 repressed the expression of two key anti-apoptotic genes of $NF{\kappa}B$, TRAF1 and TRAF2, thereby sensitizing cells to $TNF{\alpha}$-induced cell death. Taken together, our data suggest that ZAS3 is a tumor suppressor gene and therefore serves as a novel therapeutic target for developing anti-cancer drugs.

• Journal of Ginseng Research
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• v.34 no.2
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• pp.138-144
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• 2010

Ginseng (Panax ginseng C.A. Meyer) has been shown to have anti-stress effects in animal studies. However, most studies have only managed to detect altered levels of biomarkers or enzymes in blood or tissue, and the actual molecular mechanisms by which ginseng exerts these effects remain unknown. In this study, the anti-oxidative effect of Korean red ginseng (KRG) was examined in human SK-N-SH neuroblastoma cells. Incubation of SK-N-SH cells with the oxidative stressor hydrogen peroxide resulted in significant induction of cell death. In contrast, pre-treatment of cells with KRG decreased cell death significantly. To elucidate underlying mechanisms by which KRG inhibited cell death, the expression of apoptosis-related proteins was examined by Western blot analysis. KRG pre-treatment decreased the expression of the pro-apoptotic gene caspase-3, whereas it increased expression of the anti-apoptotic gene Bcl-2. Consistent with this, immunoblot analysis showed that pre-treatment of the SK-N-SH cells with KRG inhibited expression of the pro-inflammatory gene cyclooxygenase 2 (COX-2). RT-PCR analysis revealed that the repression of COX-2 expression by KRG pre-treatment occurred at the mRNA level. Taken together, our data indicate that KRG can protect against oxidative stress-induced neuronal cell death by repressing genes that mediate apoptosis and inflammation.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.08a
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• pp.77-77
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• 2020

Purple loosestrife-Lythrum anceps (Koehne) Makino is a herbaceous perennial plant belonging to the Lythraceae family. It has been used for centuries in Korea and other Asian traditional medicine. It has been showed pharmacological effects, including anti-oxidant and anti-microbial effects. However, the mechanisms underlying its anti-cancer mechanisms are not yet understood. In this study, we investigated the mechanism of apoptosis signaling pathways by ethanol extract of Lythrum anceps (Koehne) Makino (ELM) in human leukemia U937 cells. Treatment with ELM significantly inhibited cell growth in a dose-dependent manner by inducing apoptosis, as evidenced by the formation of apoptotic bodies (ApoBDs), DNA fragmentation and increased populations of sub-G1 ratio. Induction of apoptosis by ELM was connected with up-regulation of death receptor (DR) 4 and DR5, pro-apoptotic Bax protein expression and down-regulation of anti-apoptotic Bcl-2 protein, and inhibitor of apoptosis protein (IAP) family proteins (XIAP, cIAP-1, survivin), depending on dosage. This induction was associated with Bid truncation, mitochondrial dysfunction, proteolytic activation of caspases (-3, -8 and -9) and cleavage of poly(ADP-ribose) polymerase protein. Therefore, our data indicate that ELM suppresses U937 cell growth by activating the intrinsic and extrinsic apoptosis pathways, and thus may have applications as a potential source for an anti-leukemic chemotherapeutic agent.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5317-5323
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• 2013

Breast cancer is the most prevalent cancer and one of the leading causes of death among women in the world. Plants and herbs may play an important role in complementary or alternative treatment. The aim of this study was to evaluate the antioxidant and anti-proliferative potential of Urtica dioica. The anti oxidant activity of an aqueous extract of Urtica dioica leaf was measured by MTT assay and the FRAP method while its anti-proliferative activity on the human breast cancer cell line (MCF-7) and fibroblasts isolated from foreskin tissue was evaluated using MTT assay. Mechanisms leading to apoptosis were also investigated at the molecular level by measuring the amount of anti and pro-apoptotic proteins and at the cellular level by studying DNA fragmentation and annexin V staining by flow cytometry. The aqueous extract of Urtica dioica showed antioxidant effects with a correlation coefficient of $r^2$=0.997. Dose-dependent and anti-proliferative effects of the extract were observed only on MCF-7 cells after 72 hrs with an $IC_{50}$ value of 2 mg/ml. This anti proliferative activity was associated with an increase of apoptosis as demonstrated by DNA fragmentation, the appearance of apoptotic cells in flow cytometry analysis and an increase of the amount of calpain 1, calpastatin, caspase 3, caspase 9, Bax and Bcl-2, all proteins involved in the apoptotic pathway. This is the first time such in vitro antiproliferative effect of aqueous extract of Urtica dioica leaf has been described for a breast cancer cell line. Our findings warrant further research on Urtica dioica as a potential chemotherapeutic agent for breast cancer.

• BMB Reports
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• v.52 no.2
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• pp.119-126
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• 2019

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) initiates the extrinsic apoptotic pathway through formation of the death-inducing signaling complex (DISC), followed by activation of effector caspases. TRAIL receptors are composed of death receptors (DR4 and DR5), decoy receptors (DcR1 and DcR2), and osteoprotegerin. Among them, only DRs activate apoptotic signaling by TRAIL. Since the levels of DR expressions are higher in cancer cells than in normal cells, TRAIL selectively activates apoptotic signaling pathway in cancer cells. However, multiple mechanisms, including down-regulation of DR expression and pro-apoptotic proteins, and up-regulation of anti-apoptotic proteins, make cancer cells TRAIL-resistant. Therefore, many researchers have investigated strategies to overcome TRAIL resistance. In this review, we focus on protein regulation in relation to extrinsic apoptotic signaling pathways via ubiquitination. The ubiquitin proteasome system (UPS) is an important process in control of protein degradation and stabilization, and regulates proliferation and apoptosis in cancer cells. The level of ubiquitination of proteins is determined by the balance of E3 ubiquitin ligases and deubiquitinases (DUBs), which determine protein stability. Regulation of the UPS may be an attractive target for enhancement of TRAIL-induced apoptosis. Our review provides insight to increasing sensitivity to TRAIL-mediated apoptosis through control of post-translational protein expression.

• Korean Journal of Organic Agriculture
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• v.19 no.2
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• pp.245-253
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• 2011

This study was carried out to investigate the biological effects of organic soybean extracts. Cellular and molecular analysis was performed to determine anti-oxidative, anti-inflammatory, anti-apoptotic, and anti-inflammatory effects of soybean extracts. First, we obtained various solvent extracts of soybean such as water, ethanol, and methanol. Molecular and cellular analysis were performed with 0.1 mg/ml concentration of each solvent extracts. The results of anti-oxidative, antiinflammatory and anti-apoptotic effects of organic soybean extracts were prominent. However, organic soybean extracts were not observed in anti-allergic effects determined by releasing histamine from rat mast cell line, RBL-2H3. Conclusively, organic soybean suppress inflammatory responses. In addition, organic soybean could be applied as a functional food ingredient for treatment of chronic inflammation, asthma, and atopic dermatitis with enhanced anti-inflammatory activities.