• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7747-7752
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• 2014

Kr$\ddot{u}$ppel-like factor 4 is a transcription factor which plays an important role in development and progression of various carcinomas. Curcumin characterized by excellent anti-cancer properties is regarded as a serviceable natural compound used in carcinoma therapy. This study aimed at exploring the impact of KLF4 overexpression in cooperation with curcumin on the proliferation, apoptosis and invasion of human gastric carcinoma BGC-823 cells. Flow cytometry analysis, CCK-8 assays, transwell assays and Western blot results showed that KLF4 overexpression combined with curcumin had significant anti-proliferation, pro-apoptosis and anti-invasion effects on BGC-823 cells. We also found that KLF4 had synergistic effects with curcumin, better promoting apoptosis and inhibiting proliferation and invasion of gastric carcinona cells. These results indicate that KLF4 could be used as a potential therapeutic target; curcumin could act as an auxiliary and provide a promising therapeutic strategy in stomach cancer.

• Biomolecules & Therapeutics
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• v.25 no.2
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• pp.165-170
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• 2017

Cordyceps bassiana is one of Cordyceps species with anti-oxidative, anti-cancer, anti-inflammatory, anti-diabetic, anti-obesity, anti-angiogenic, and anti-nociceptive activities. This mushroom has recently demonstrated to have an ability to reduce 2,4-dinitrofluorobenzene-induced atopic dermatitis symptoms in NC/Nga mice. In this study, we further examined phytochemical properties of this mushroom by column chromatography and HPLC analysis. By chromatographic separation and spectroscopic analysis, 8 compounds, such as 1,9-dimethylguanine (1), adenosine (2), uridine (3), nicotinamide (4), 3-methyluracil (5), 1,7-dimethylxanthine (6), nudifloric acid (7), and mannitol (8) were identified from 6 different fractions and 4 more subfractions. Through evaluation of their anti-inflammatory activities using reporter gene assay and mRNA analysis, compound 1 was found to block luciferase activity induced by $NF-{\kappa}B$ and AP-1, suppress the mRNA levels of cyclooxygenase (COX)-2 and tumor necrosis factor $(TNF)-{\alpha}$. Therefore, our data strongly suggests that compound 1 acts as one of major principles in Cordyceps bassiana with anti-inflammatory and anti-atopic dermatitis activities.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9049-9058
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• 2014

Casticin (3', 5-dihydroxy-3, 4', 6, 7-tetramethoxyflavone) is an active compound isolated from roots, stems, leaves, fruits and seeds of a variety of plants. It is well known for its pharmacological properties and has been utilized as an anti-hyperprolactinemia, anti-tumor, anti-inflammatory, neuroprotetective, analgesic and immunomodulatory agent. Recently, the anticancer activity of casticin has been extensively investigated. The resulkts showed that it exerts protective potential by targeting apoptosis, considered important for cancer therapies. In this article, our aim was to review the pharmacological and therapeutic applications of casticin with specific emphasis on its anticancer functions and related molecular mechanisms. Chemotherapeutic effects are dependent on multiple molecular pathways, which may provide a new perspective of casticin as a candidate anti-neoplastic drug. This review suggests that additional studies and preclinical trials are required to determine specific intracellular sites of action and derivative targets in order to fully understand the mechanisms of its antitumor activity and validate this compound as a medicinal agent for the prevention and treatment of various cancers.

• Molecules and Cells
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• v.40 no.4
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• pp.291-298
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• 2017

MicroRNAs (miRNAs) are short non-coding RNAs that regulate genes posttranscriptionally. Past studies have reported that miR-210 is up-regulated in many cancers including cervical cancer, and plays a pleiotropic role in carcinogenesis. However, its role in regulating response towards anti-cancer agents has not been fully elucidated. We have previously reported that the natural compound 1'S-1'-acetoxychavicol acetate (ACA) is able to induce cytotoxicity in various cancer cells including cervical cancer cells. Hence, this study aims to investigate the mechanistic role of miR-210 in regulating response towards ACA in cervical cancer cells. In the present study, we found that ACA down-regulated miR-210 expression in cervical cancer cells, and suppression of miR-210 expression enhanced sensitivity towards ACA by inhibiting cell proliferation and promoting apoptosis. Western blot analysis showed increased expression of mothers against decapentaplegic homolog 4 (SMAD4), which was predicted as a target of miR-210 by target prediction programs, following treatment with ACA. Luciferase reporter assay confirmed that miR-210 binds to sequences in 3'UTR of SMAD4. Furthermore, decreased in SMAD4 protein expression was observed when miR-210 was overexpressed. Conversely, SMAD4 protein expression increased when miR-210 expression was suppressed. Lastly, we demonstrated that overexpression of SMAD4 augmented the anti-proliferative and apoptosis-inducing effects of ACA. Taken together, our results demonstrated that down-regulation of miR-210 conferred sensitivity towards ACA in cervical cancer cells by targeting SMAD4. These findings suggest that combination of miRNAs and natural compounds could provide new strategies in treating cervical cancer.

• Mycobiology
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• v.51 no.4
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• pp.246-255
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• 2023

Genus Penicillium comprising the most important and extensively studied fungi has been well-known as a rich source of secondary metabolites. Our study aimed to analyze and investigate biological activities, including in vitro anti-cancer, anti-inflammatory and anti-diabetic properties, of metabolites from a marine-derived fungus belonging to P. levitum. The chemical compounds in the culture broth of P. levitum strain N33.2 were extracted with ethyl acetate. Followingly, chemical analysis of the extract leaded to the isolation of three ergostane-type steroid components, namely cerevisterol (1), ergosterol peroxide (2), and (3β,5α,22E)-ergosta-6,8(14),22-triene-3,5-diol (3). Among these, (3) was the most potent cytotoxic against human cancer cell lines Hep-G2, A549 and MCF-7 with IC₅₀ values of 2.89, 18.51, and 16.47 ㎍/mL, respectively, while the compound (1) showed no significant effect against tested cancer cells. Anti-inflammatory properties of purified compounds were evaluated based on NO-production in LPS-induced murine RAW264.7 macrophages. As a result, tested compounds performed diverse inhibitory effects on NO production by the macrophages, with the most significant inhibition rate of 81.37±1.35% at 25 ㎍/mL by the compound (2). Interestingly, compounds (2) and (3) exhibited inhibitory activities against pancreatic lipase and α-glucosidase enzymes in vitro assays. Our study brought out new data concerning the chemical properties and biological activities of isolated steroids from a P. levitum fungus.

• Journal of Pharmaceutical Investigation
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• v.37 no.5
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• pp.305-309
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• 2007

Arsenic compounds have been used to treat various diseases including cancer in oriental medicine. Arsenic trioxide ($As_2O_3,\;Trisenox^{(R)}$) has been used for the treatment of leukemia and its anti-solid tumor activity has also been reported recently. Tetra-arsenic oxide ($As_4O_6,\;TetraAs^{(R)}$) is a newly developed arsenic compound which has shown an anticancer activity in some human cancer cell lines. The purpose of this study was to evaluate the anti-gastric cancer potential of TetraAs and to search for an agent with synergistic interaction with TetraAs against human gastric cancers. We analysed anti-proliferative effect of TetraAs when given alone and in combination with other chemotherapeutic agents such as 5-FU, paclitaxel, and cisplatin in SNU-216, a human gastric cancer cell line. The $IC_{50}$ of these 4 anti-cancer drugs ranged from 5.8 nM to $7.5\;{\mu}M$ with a potency rank of order paclitaxel>TetraAs>cisplatin>5-FU. TetraAs showed 10-fold greater potency than 5-FU and cisplatin at the same effect level of $IC_{50}$. TetraAs+5-FU and TetraAs+paclitaxel showed synergistic and additive interaction, respectively. On the other hand, TetraAs with cisplatin group appeared to be strongly antagonistic. Apoptotic population was measured and compared between single and combination treatment. The apoptotic cells for the combination of TetraAs+5-FU showed significant increase compared to single TetraAs treatment. On the contrary, TetraAs+cisplatin showed less apoptotic cells compared to TetraAs or cisplatin alone treatment. Overall, our results indicate that TetraAs can be effectively combined with 5-FU or paclitaxel, but not with cisplatin for synergistic anti-cancer effect, which warrants further evaluation using in vivo models.

• Biomolecules & Therapeutics
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• v.23 no.4
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• pp.367-373
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• 2015

Cordyceps species including Cordyceps bassiana are a notable anti-cancer dietary supplement. Previously, we identified several compounds with anti-cancer activity from the butanol fraction (Cb-BF) of Cordyceps bassiana. To expand the structural value of Cb-BF-derived anti-cancer drugs, we employed various chemical moieties to produce a novel Cb-BF-derived chemical derivative, KTH-13-amine-monophenyl [4-isopropyl-2-(1-phenylethyl) aniline (KTH-13-AMP)], which we tested for anti-cancer activity. KTH-13-AMP suppressed the proliferation of MDA-MB-231, HeLa, and C6 glioma cells. KTH-13-AMP also dose-dependently induced morphological changes in C6 glioma cells and time-dependently increased the level of early apoptotic cells stained with annexin V-FITC. Furthermore, the levels of the active full-length forms of caspase-3 and caspase-9 were increased. In contrast, the levels of total forms of caspases-3, caspase-8, caspase-9, and Bcl-2 were decreased in KTH-13-AMP treated-cells. We also confirmed that the phosphorylation of STAT3, Src, and PI3K/p85, which is linked to cell survival, was diminished by treatment with KTH-13-AMP. Therefore, these results strongly suggest that this compound can be used to guide the development of an anti-cancer drug or serve as a lead compound in forming another strong anti-proliferative agent.

• Nutrition Research and Practice
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• v.8 no.3
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• pp.257-266
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• 2014

BACKGROUND/OBJECTIVE: Licorice has been shown to possess cancer chemopreventive effects. However, glycyrrhizin, a major component in licorice, was found to interfere with steroid metabolism and cause edema and hypertension. The roasting process of licorice modifies the chemical composition and converts glycyrrhizin to glycyrrhetinic acid. The purpose of this study was to examine the anti-carcinogenic effects of the ethanol extract of roasted licorice (EERL) and to identify the active compound in EERL. MATERIALS/METHODS: Ethanol and aqueous extracts of roasted and un-roasted licorice were prepared. The active fraction was separated from the methylene chloride (MC)-soluble fraction of EERL and the structure of the purified compound was determined by nuclear magnetic resonance spectroscopy. The anti-carcinogenic effects of licorice extracts and licochalcone A was evaluated using a MTT assay, Western blot, flow cytometry, and two-stage skin carcinogenesis model. RESULTS: EERL was determined to be more potent and efficacious than the ethanol extract of un-roasted licorice in inhibiting the growth of DU145 and MLL prostate cancer cells, as well as HT-29 colon cancer cells. The aqueous extracts of un-roasted and roasted licorice showed minimal effects on cell growth. EERL potently inhibited growth of MCF-7 and MDA-MB-231 breast, B16-F10 melanoma, and A375 and A2058 skin cancer cells, whereas EERL slightly stimulated the growth of normal IEC-6 intestinal epithelial cells and CCD118SK fibroblasts. The MC-soluble fraction was more efficacious than EERL in inhibiting DU145 cell growth. Licochalcone A was isolated from the MC fraction and identified as the active compound of EERL. Both EERL and licochalcone A induced apoptosis of DU145 cells. EERL potently inhibited chemically-induced skin papilloma formation in mice. CONCLUSIONS: Non-polar compounds in EERL exert potent anti-carcinogenic effects, and that roasted rather than un-roasted licorice should be favored as a cancer preventive agent, whether being used as an additive to food or medicine preparations.

• Journal of Nutrition and Health
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• v.37 no.1
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• pp.31-37
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• 2004

Curcumin, a natural compound extracted from rhizomes of Curcuma longa, has been shown to possess potent anti-inflammatory and anti-tumor activity. The mechanism by which curcumin initiates apoptosis remains poorly understood. In this study, we investigated the effects of curcumin on caspase-3 activity and protein expression of procaspase-3, Bcl-2, Bax, total Akt and phosphorylated Akt in SW480 human colon cancer cell. We cultured SW480 cells in the presence of various concentrations (0, 10, 20 or 30 uM) of curcumin. Curcumin inhibited colon cancer cell growth in a dose-dependent manner (p < 0.05). Caspase-3 activity was significantly increased dose-dependently in cells treated with curcumin (p < 0.05), concisely procaspase-3 expression was significantly decreased. Bcl-2 levels were decreased dose-dependently in cells treated with curcumin (p < 0.05), but Ben remained unchanged. In addition, phosphorylated Akt levels and total Akt levels were markedly lower in cells treated with 20 uM of curcumin treatment (p < 0.05), In conclusion, we have shown that curcumin inhibits cell growth and induces apoptosis in SW480 human colon cancer cell lines via Akt signal pathway.

• Bulletin of the Korean Chemical Society
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• v.35 no.12
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• pp.3623-3626
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• 2014

Nuclear factor-erythroid 2-related factor 2 (Nrf2) regulates the expression of over 200 genes of antioxidant and phase II drug-metabolizing enzymes, and is highly expressed in non-small cell lung cancer (NSCLC). Nine derivatives of 4-(2-cyclohexylethoxy)aniline were designed. Our previous study demonstrated that IM3829 increases radiosensitivity of several lung cancer cells in vitro and in vivo. Here, biological effects of IM3829 derivatives (2a-2i) were evaluated. Compound 2g derivative effectively inhibits mRNA and protein expression of Nrf2 and HO-1. In addition, we observed over two fold enhancement in IR-induced cell death, from $2.90{\pm}0.22$ to $6.02{\pm}0.87$, in H1299 cancer cell-line. Among the nine derivatives, compound 2g derivative exhibited the highest enhancement of radiosensitizing effect via inhibition of Nrf2 activity.