• Korean Journal of Pharmacognosy
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• v.45 no.2
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• pp.174-180
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• 2014

D-Pinitol, an anti-diabetic substance, is a naturally occurring compound found in legumes. In this study, we investigated the inhibitory effect of D-pinitol on growth and recurrence of breast cancer. When D-pinitol was treated on MDA-MB-231 or MCF-7 breast cancer cells, it was observed that the viability of the two cancer cell lines was reduced in MTT assay. In order to examine the effect on the growth of breast tumor, mouse xenograft assay was carried out. On day 0, nine millions cells of MDA-MB-231 were injected subcutaneously into nude mouse and D-pinitol was administered orally at the dose of 500 mg/kg or 1000 mg/kg body weight for consecutive 45 days. Tumor size was reduced in dose-dependent manner upto 95.4% in 1000 mpk-treated group, compared with the non-treated control group. When D-pinitol was co-administrated with $4{\mu}g$ of doxorubicin, recurrence of breast tumor was delayed by two weeks, compared with the mouse group of doxorubicin monotherapy. Consistent with this data, it was observed that the population of cancer stem cells (CSCs), responsible for recurrence of cancer, within tumor mass was significantly reduced. Taken together, D-pinitol inhibits the growth of breast cancer and relapse of the tumor by suppressing the proliferation of CSCs.

• Molecules and Cells
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• v.45 no.6
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• pp.425-434
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• 2022

The post-translational modification (e.g., phosphorylation) of estrogen receptor α (ERα) plays a role in controlling the expression and subcellular localization of ERα as well as its sensitivity to hormone response. Here, we show that ERα is also modified by UFM1 and this modification (ufmylation) plays a crucial role in promoting the stability and transactivity of ERα, which in turn promotes breast cancer development. The elevation of ufmylation via the knockdown of UFSP2 (the UFM1-deconjugating enzyme in humans) dramatically increases ERα stability by inhibiting ubiquitination. In contrast, ERα stability is decreased by the prevention of ufmylation via the silencing of UBA5 (the UFM1-activating E1 enzyme). Lys171 and Lys180 of ERα were identified as the major UFM1 acceptor sites, and the replacement of both Lys residues by Arg (2KR mutation) markedly reduced ERα stability. Moreover, the 2KR mutation abrogated the 17β-estradiol-induced transactivity of ERα and the expression of its downstream target genes, including pS2, cyclin D1, and c-Myc; this indicates that ERα ufmylation is required for its transactivation function. In addition, the 2KR mutation prevented anchorage-independent colony formation by MCF7 cells. Most notably, the expression of UFM1 and its conjugating machinery (i.e., UBA5, UFC1, UFL1, and UFBP1) were dramatically upregulated in ERα-positive breast cancer cell lines and tissues. Collectively, these findings implicate a critical role attributed to ERα ufmylation in breast cancer development by ameliorating its stability and transactivity.

• Journal of Microbiology and Biotechnology
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• v.32 no.9
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• pp.1195-1208
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• 2022

Silver nanoparticles (AgNPs) have potential applications in medicine, photocatalysis, agriculture, and cosmetic fields due to their unique physicochemical properties and strong antimicrobial activity. Here, AgNPs were synthesized using actinobacterial SL19 strain, isolated from acidic forest soil in Poland, and confirmed by UV-vis and FTIR spectroscopy, TEM, and zeta potential analysis. The AgNPs were polydispersed, stable, spherical, and small, with an average size of 23 nm. The FTIR study revealed the presence of bonds characteristic of proteins that cover nanoparticles. These proteins were then studied by using liquid chromatography with tandem mass spectrometry (LC-MS/MS) and identified with the highest similarity to hypothetical protein and porin with molecular masses equal to 41 and 38 kDa, respectively. Our AgNPs exhibited remarkable antibacterial activity against Escherichia coli and Pseudomonas aeruginosa. The combined, synergistic action of these synthesized AgNPs with commercial antibiotics (ampicillin, kanamycin, streptomycin, and tetracycline) enabled dose reductions in both components and increased their antimicrobial efficacy, especially in the case of streptomycin and tetracycline. Furthermore, the in vitro activity of the AgNPs on human cancer cell lines (MCF-7, A375, A549, and HepG2) showed cancer-specific sensitivity, while the genotoxic activity was evaluated by Ames assay, which revealed a lack of mutagenicity on the part of nanoparticles in Salmonella Typhimurium TA98 strain. We also studied the impact of the AgNPs on the catalytic and photocatalytic degradation of methyl orange (MO). The decomposition of MO was observed by a decrease in intensity of absorbance within time. The results of our study proved the easy, fast, and efficient synthesis of AgNPs using acidophilic actinomycete SL19 strain and demonstrated the remarkable potential of these AgNPs as anticancer and antibacterial agents. However, the properties and activity of such particles can vary by biosynthesized batch.

• Korean Journal of Medicinal Crop Science
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• v.12 no.3
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• pp.243-248
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• 2004

Essential oils from Needl Juniperrus seed and trunk (Juniperrus rigida Sieb.) and Olibanum resin (Boswellia carteii Birew) were extracted by a supercritical fluid extraction system (SFE) and immune activity of each essential oils were observed. The immune activities of each essential oil were compared. Essential oil from Olibanum resin enhanced the growth of human immune T cell up to 1.33 times, compared to control group. Each essential oils showed the potent inhibitory effect on the human cancer cell lines, and increased the secretion of cytokines, IL-6 and $TNF-{\alpha}$ from human B cell as well as the growth of human immune cells.

• Korean Journal of Medicinal Crop Science
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• v.12 no.4
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• pp.309-314
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• 2004

The cytotoxic effects of water and ethanol extracts of Echinacea purpurea (L.) (EP) and chloroform, ethyl acetate, butanol and aqueous fractions from each extract of EP were examined. Every extract and fraction of EP inhibited the growth of human hepatocarcinoma, human gastric cancer cell, human breast cancer cells and human lung carcunoma in concentration-dependent manners over a concentration range of $0.05{\sim}1.0\;mg/ml$. Most extracts and fractions with the concentraction of 1 mg/ml showed strong inhibition of more than 70% for every cancer cell. Only aqueous fractions of each extract showed very weak inhibitons of 12 to 25% on the growth of human normal lung cell with the concentration of 1 mg/ml. Overall selectivity of the extrats and fractions on the four human cancer cell lines was over 2.5. These results indicate that EP has a very potent selective toxicity for cancer cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.29 no.1
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• pp.147-152
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• 2000

Various lines of evidence suggest that dietary components protect the initiation of carcinogenesis. In this study, the ethanol extracts (AGE) and the methanol and hexane partition layers (AGEM, AGEH) of the Angelica radix were screened for their cytotoxic effects using the MTT assay on HepG2, HeLa, MCF7 and SW626 cells and for their ability to induce quinone reductase (QR) in HepG2 cells. AGEM and AGEH of the Angelica radix showed the strongest cytotoxic effects on HepG2 and HeLa cells. Cell growth was inhibited by 99.8% and 99.8% on HepG2 cells and 99.3% and 99.4% on HeLa cells, at dose of $100\;\mu\textrm{g}/ml$ of AGEM and AGEH extracts respectively. AGE and AGEH significantly induced QR activities in the HepG2 cells. The QR activities of HepG2 cells grown in the presence of AGE, AGEH, and AGEM at the concentration of $50\;\mu\textrm{g}/mL$ were 313.5, 273.3 and 133.3 nmol/min/mg protein, respectively. Therefore, based on these studies, Angelica radix may be developed into a potentially useful cancer chemopreventive agent.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.685-690
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• 2002

The mitogen-stimulated serine/threonine kinase $p70^{S6k}$ plays an important role in the progression of cells from $G_0/G$_1$$ to S phase of the cell cycle by translational up-regulation of a family of mRNA transcripts family of mRNA transcripts which contain polypyrimidine tract at their 5 transcriptional start site. Here, we report that $p70^{S6k}$ was constitutively phosphorylated and activated to various degrees in serum-deprived AGS, A2058, HT-1376, MG63, MCF7, MDA-MB-435S, MDA-MB-231 and MB-157. Rapamycin treatment induced a significant dephosphorylation and inactivation of $p70^{S6k}$ in all cancer cell lines, while wortmannin, a specific inhibitor of PI3-K, caused a mild dephosphorylation of $p70^{S6k}$ in AGS, MDA-MB-435S and MB-157. In addition, SQ20006, methylxanthine phosphodiesterase inhibitor, reduced the phosphorylation of $p70^{S6k}$ in all cancer cells tested. Consistent with inhibitory effect of rapamycin on $p70^{S6k}$ activity, rapamycin inhibited [$^3H$]-thymidine incorporation and increased the number of cells at $G_{0}G_{1}$ phase. Furthermore, these inhibitory effects were accompanied by the decrease in growth of cancer cells. Taken together, the results indicate that the antiproliferative activity of rapamycin might be attributed to cell cycle arrest at $G_{0}G_{1}$ phase in human cancer cells through the inhibition of constitutively activated $p70^{S6k}$ of cancer cells and suggest $p70^{S6k}$ as a potential target for therapeutic strategies aimed at preventing or inhibiting tumor growth.

• Korean Journal of Medicinal Crop Science
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• v.13 no.4
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• pp.199-205
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• 2005

This study was carried out to investigate the effect of 70% ethanol extract and each fraction from Rhododendron brachycarpum D. Don leaves on cytotoxicity, anticancer, genotoxicity and immunological activity in vitro bioassay. Cytotoxicity for human normal cells (HEL299 and Chang) of the samples was shown below 35% in 0.5 mg/ml concentration of samples except aqueous fraction by SRB assay. DNA damage on the Chang cell of the samples alone in comet assay was observed very weak damage activity even in high concentration (1 mg/ml) of the samples. The anticancer effect of the samples on human cancer cell lines (A549, AGS, Hep3B, MCF7) was indicated that the cancer cells were inhibited gradually in proportion to the increase of the concentration of the samples by MTT assay. The growth of the Raji and Jurkat cells were hastened by adding butanol fraction among the samples. In the genotoxicity on $H_2O_2-induced$ DNA damage in Chang cells using alkaline comet assay, most of samples were shown a strong protective activity from DNA OTM values.

• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.340-347
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• 2022

Advanced or metastatic breast cancer affects multiple organs and is a leading cause of cancer-related death. Cancer metastasis is associated with epithelial-mesenchymal metastasis (EMT). However, the specific signals that induce and regulate EMT in carcinoma cells remain unclear. PRR16/Largen is a cell size regulator that is independent of mTOR and Hippo signalling pathways. However, little is known about the role PRR16 plays in the EMT process. We found that the expression of PRR16 was increased in mesenchymal breast cancer cell lines. PRR16 overexpression induced EMT in MCF7 breast cancer cells and enhances migration and invasion. To determine how PRR16 induces EMT, the binding proteins for PRR16 were screened, revealing that PRR16 binds to Abl interactor 2 (ABI2). We then investigated whether ABI2 is involved in EMT. Gene silencing of ABI2 induces EMT, leading to enhanced migration and invasion. ABI2 is a gene that codes for a protein that interacts with ABL proto-oncogene 1 (ABL1) kinase. Therefore, we investigated whether the change in ABI2 expression affected the activation of ABL1 kinase. The knockdown of ABI2 and PRR16 overexpression increased the phosphorylation of Y412 in ABL1 kinase. Our results suggest that PRR16 may be involved in EMT by binding to ABI2 and interfering with its inhibition of ABL1 kinase. This indicates that ABL1 kinase inhibitors may be potential therapeutic agents for the treatment of PRR16-related breast cancer.

• Journal of Life Science
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• v.29 no.10
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• pp.1062-1070
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• 2019

A components of garlic (Allium sativum) have anti-proliferative effects against various types of cancer. We aimed to investigate the capacity of garlic compounds to anti-tumor on a various cancer cell lines. Fractionation of garlic extract, guided by antiproliferative activity against human gastric cancer (AGS) cells, has resulted in the isolation of N-benzyl-N-methyldecan-1-amine (NBNMA). We investigated the effect of newly isolated NBNMA from garlic cloves on the inhibition of the growth of CT-26, AGS, HepG2, HCT-116, MCF7, B16F10, and Sarcoma-180 cells for in vitro and CT-26 colon carcinoma cells in vivo. NBNMA exhibited an antiproliferative effect in CT-26 cells by apoptotic cell death. NBNMA exhibited down-regulation of anti-apoptotic Bcl-2 proteins and up-regulation of apoptotic Bad protein expression in western blot analyses. In addition, NBNMA meagre activated caspase 3 and caspase 9, initiator caspases of the extrinsic and intrinsic pathways of apoptosis. NBNMA treatment at a dose of 10 mg/kg for 21 days in experimental mice implanted with tumors resulted in significant reduction of the tumor weight (43%). NBNMA exhibited both in vitro and in vivo anticancer activity. These results indicate that NBNMA has promising potential to become a novel anticancer agent from garlic cloves for the treatment of colon carcinoma cancer.