• The Korean Journal of Physiology and Pharmacology
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• v.15 no.5
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• pp.279-283
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• 2011

Quercetin (3,3',4',5,7-pentahydroxyflavone) is an attractive therapeutic flavonoid for cancer treatment because of its beneficial properties including apoptotic, antioxidant, and antiproliferative effects on cancer cells. However, the exact mechanism of action of quercetin on ion channel modulation is poorly understood in bladder cancer 253J cells. In this study, we demonstrated that large conductance $Ca^{2+}$-activated $K^+$ ($BK_{Ca}$) or MaxiK channels were functionally expressed in 253J cells, and quercetin increased $BK_{Ca}$ current in a concentration dependent and reversible manner using a whole cell patch configuration. The half maximal activation concentration ($IC_{50}$) of quercetin was $45.5{\pm}7.2{\mu}m$. The quercetin-evoked $BK_{Ca}$ current was inhibited by tetraethylammonium (TEA; 5 mM) a non-specific $BK_{Ca}$ blocker and iberiotoxin (IBX; 100 nM) a $BK_{Ca}$-specific blocker. Quercetin-induced membrane hyperpolarization was measured by fluorescence-activated cell sorting (FACS) with voltage sensitive dye, bis (1,3-dibutylbarbituric acid) trimethine oxonol ($DiBAC_4$2(3); 100 nM). Quercetin-evoked hyperpolarization was prevented by TEA. Quercetin produced an antiproliferative effect ($30.3{\pm}13.5%$) which was recovered to $53.3{\pm}10.5%$ and $72.9{\pm}3.7%$ by TEA and IBX, respectively. Taken together our results indicate that activation of $BK_{Ca}$ channels may be considered an important target related to the action of quercetin on human bladder cancer cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.4
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• pp.966-972
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• 2006

The effect of water extract of Chungjogupae-tang (CJGPT) was investigated _on the growth of human lung carcinoma A549 cells. Methods: MTT assay and fluorescent microscope peformed to compare and examine the efficacy of CJGPT treatment on the cytostaticity of lung cancer cells in proportion to time and doses, and DAPI staining and Western blot analysis were used to examine their effect on apoptosis. In addition, the quantitative RT-PCR was used to examine to lung cancer cells growth, and Prostaglandin E2 activity were measured. Results: Exposure of A549 cells to CJGPT respited in the growth inhibition and apoptosis in a dose-dependent manner as measured by MTT assay and fluorescent microscope. The antiproliferative effect by CJGPT treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. CJGPT treatment resulted in an up-regulation of cyclin-dependent kinase inhibitor p21 (WAFl/CIPl) in a p53-independent fashion. We found that CJGPT treatment decreased the levels of cyclooxygenase (COX)-2 and inducible nitric oxide synthease (iNOS) expression without significant changes in the expression of COX-1 , which was correlated with a decrease in prostaglandin E2 (PGE2) synthesis. Conclusion: These findings suggested that CJGPT-induced inhibition of human lung carcinoma A549 cell growth was connected with the induction of apoptotic cell death and the results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of CJGPT.

• Biomolecules & Therapeutics
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• v.30 no.1
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• pp.72-79
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• 2022

Licochalcone H (LCH) is a phenolic compound synthetically derived from licochalcone C (LCC) that exerts anticancer activity. In this study, we investigated the anticancer activity of LCH in human skin cancer A375 and A431 cells. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) cell viability assay was used to evaluate the antiproliferative activity of LCH. Cell cycle distribution and the induction of apoptosis were analyzed by flow cytometry. Western blotting assays were performed to detect the levels of proteins involved in cell cycle progression, apoptosis, and the JAK2/STAT3 signaling pathway. LCH inhibited the growth of cells in dose- and time-dependent manners. The annexin V/propidium iodide double staining assay revealed that LCH induced apoptosis, and the LCH-induced apoptosis was accompanied by cell cycle arrest in the G1 phase. Western blot analysis showed that the phosphorylation of JAK2 and STAT3 was decreased by treatment with LCH. The inhibition of the JAK2/STAT3 signaling pathway by pharmacological inhibitors against JAK2/STAT3 (cryptotanshinone (CTS) and S3I-201) simulated the antiproliferative effect of LCH suggesting that LCH induced apoptosis by modulating JAK2/STAT3 signaling.

• Natural Product Sciences
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• v.28 no.3
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• pp.121-129
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• 2022

Despite considerable efforts, cancer remains an aggressive killer worldwide. Chemotherapeutic drugs that are currently in use lead to destructive side effects and have not succeeded in fulfilling expectations. For centuries, medicinal plants are used for treating various diseases and are also known to have anticancer activity. The main aim of this research was to evaluate antiproliferative activity of saffron, clove, fenugreek, and green tea on Vero and MDA-MB-231 cell lines and to subsequently analyze the effect of these extracts on IRAK-4, TAK1, IKK-alpha, IKK-beta, NF-Kappa B, IRF3, IRF7 genes in Toll Like Receptors (TLRs) pathway. Antiproliferative assay was done by Neutral Red Dye uptake assay. Methanolic extract of green tea was found to be most effective against both cell lines as IC₅₀ was achieved at least concentration of the extract. For molecular studies, MDAMB-231 cells were sensitized with methanolic extract of green tea at same IC₅₀, and RT-PCR was performed to determine the relative expression of genes. Expression of IRAK-4, TAK1, IKK-beta, NF-Kappa B, IRF3 genes was down regulated and IRF7 and IKKalpha was upregulated. Green tea has a potential cytotoxic effect on both cell lines which was demonstrated by its effect on the expression of (TLRs) pathway genes.

• International Journal of Stem Cells
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• v.16 no.3
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• pp.315-325
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• 2023

Background and Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor characterized by its heterogeneity and high recurrence and lethality rates. Glioblastoma stem cells (GSCs) play a crucial role in therapy resistance and tumor recurrence. Therefore, targeting GSCs is a key objective in developing effective treatments for GBM. The role of Parathyroid hormone-related peptide (PTHrP) in GBM and its impact on GSCs remains unclear. This study aimed to investigate the effect of PTHrP on GSCs and its potential as a therapeutic target for GBM. Methods and Results: Using the Cancer Genome Atlas (TCGA) database, we found higher expression of PTHrP in GBM, which correlated inversely with survival. GSCs were established from three human GBM samples obtained after surgical resection. Exposure to recombinant human PTHrP protein (rPTHrP) at different concentrations significantly enhanced GSCs viability. Knockdown of PTHrP using target-specific siRNA (siPTHrP) inhibited tumorsphere formation and reduced the number of BrdU-positive cells. In an orthotopic xenograft mouse model, suppression of PTHrP expression led to significant inhibition of tumor growth. The addition of rPTHrP in the growth medium counteracted the antiproliferative effect of siPTHrP. Further investigation revealed that PTHrP increased cAMP concentration and activated the PKA signaling pathway. Treatment with forskolin, an adenylyl cyclase activator, nullified the antiproliferative effect of siPTHrP. Conclusions: Our findings demonstrate that PTHrP promotes the proliferation of patient-derived GSCs by activating the cAMP/PKA signaling pathway. These results uncover a novel role for PTHrP and suggest its potential as a therapeutic target for GBM treatment.

• Journal of Applied Biological Chemistry
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• v.52 no.4
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• pp.180-186
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• 2009

Whole plants of Vitex rotundifolia were extracted for 2 days with methylene chloride ($CH_2Cl_2$) followed by extraction of the residue for an additional 2 days. The same procedure was also applied using methanol (MeOH). The two crude extracts were combined and partitioned between $CH_2Cl_2$ and $H_2O$. The organic layer was further partitioned between n-hexane and 85% aq. MeOH, and the aqueous layer was also further fractionated with n-BuOH and $H_2O$, successively. From the 85% aq. MeOH fraction, one compound was isolated through the repeated HPLC. According to the results of physicochemical data including NMR and MS, the chemical structure of the compound was determined as artemetin (1). The antiproliferative effects of the crude extracts, fractions, and compound against HT1080, AGS, MCF-7 and HT-29 human cancer cells were compared with the control by using MTT assay. In the comparative analysis, the 85% aq. MeOH fraction exhibited the strongest antiproliferative effects on human cancer cell lines in a dose-dependent manner (p<0.05). In addition, exposure of compound 1 isolated from 85% aq. MeOH fraction led to strong antiproliferative effect in HT1080 cancer cell lines. These results suggest that the extracts and compound isolated from V. rotundifolia may be used as potential chemopreventive and chemotherapeutic agents.

• Journal of Microbiology and Biotechnology
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• v.17 no.8
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• pp.1227-1235
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• 2007

Lactic acid bacteria (LAB) provide several potential health and nutritional benefits, including improving the nutritional value of food, controlling serum cholesterol levels, and controlling some types of cancer. Numerous in vitro, in vivo, human, and epidemiological studies have provided evidence of the chemopreventive effects of LAB on colon, bladder, liver, breast, and gastric cancers. These effects act via diverse mechanisms, including alteration of the gastrointestinal micro flora, enhancement of the host's immune response, and antioxidative and antiproliferative activities. This review discusses the recent progresses on the chemopreventive effects of LAB on specific cancer types and the underlying molecular mechanisms.

• Food Science and Biotechnology
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• v.17 no.2
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• pp.228-233
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• 2008

Considerable progress has been made in functionalization of the soy isoflavones through enzymatic modification of daidzin, genistin, and glycitin. After hydrolysis of $\beta$-glucosides into their corresponding aglycones, these compounds were structurally modified via biotransformations such as regioselective hydroxylation, enantioselective reduction, regioselective methylation, and polymerization. These reactions often resulted in an increase of the biological activities (e.g., anti oxidative activity, antiproliferative activity) and/or improvement of the physico-chemcial properties (e.g., water solubility, bioavailability). This review briefly summarizes on-going research activities on the biofunctionalization of the soy isoflavones.

• Bulletin of the Korean Chemical Society
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• v.33 no.2
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• pp.535-540
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• 2012

A series of benzamide-based histone deacetylases (HDACs) inhibitors possessing N-(aminopyridine) residue as the zinc binding site of HDAC were synthesized and evaluated. Among these derivatives, compounds with N-(2-amino-4-pyridine) benzamide moiety have been found as the most potent ones. Moreover, introduction of appropriate substituents on the terminal aryl group acting as the surface-recognition domain could significantly improve the antiproliferative activity. In particular, the compound 4k possessed favorable pharmacokinetic characteristics and exhibited potent antitumor activity on xenograft model in mice at well tolerated doses, thus suggesting a good therapeutic index.

• Bulletin of the Korean Chemical Society
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• v.33 no.9
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• pp.2991-2998
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• 2012

A series of new diarylureas and diarylamides possessing 1,3,4-triarylpyrazole scaffold was synthesized and their in vitro antiproliferative activities against A375P human melanoma cell line and NCI-60 cell line panel were tested. Compounds 9, 11, 12, 14, and 17-21 showed superior potency against A375P to Sorafenib. Over the NCI-60 cancer cell line panel, compound 14 possessing a methoxy group, amide linker, and 4-chloro-3-(trifluoromethyl)phenyl terminal ring showed the highest potency and broad-spectrum anticancer activity. Compound 13 showed high selectivity towards leukemia subpanel over other cancer types.