• Natural Product Sciences
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• 제25권1호
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• pp.28-33
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• 2019

A popular approach for the study of estrogen receptor ${\alpha}$ inhibition is to investigate the protein-protein interaction between the estrogen receptor (ER) and the coactivator surface. In our study, we investigated phytochemicals from Rubus coreanus that were able to disrupt $ER{\alpha}$ and coactivator interaction with an $ER{\alpha}$ antagonist. The E-screen assay and molecular docking analysis were performed to evaluate the effects of the estrogenic activity of R. coreanus extract and its constituents on the MCF-7 human breast cancer cell line. At $100{\mu}g/mL$, R. coreanus extract significantly stimulated cell proliferation ($574.57{\pm}8.56%$). Sanguiin H6, which was isolated from R. coreanus, demonstrated the strongest affinity for the $ER{\alpha}$ coactivator-binding site in molecular docking analysis, with a binding energy of -250.149. The initial results of the study indicated that sanguiin H6 contributed to the estrogenic activity of R. coreanus through the activation of the $ER{\alpha}$ coactivator-binding site.

• Genomics & Informatics
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• 제19권4호
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• pp.39.1-39.8
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• 2021

Tamoxifen (TAM) is an anticancer drug used to treat estrogen receptor (ER)-positive breast cancer. However, its ER-independent cytotoxic and antifungal activities have prompted debates on its mechanism of action. To achieve a better understanding of the ER-independent antifungal action mechanisms of TAM, we systematically identified TAM-sensitive genes through microarray screening of the heterozygous gene deletion library in fission yeast (Schizosaccharomyces pombe). Secondary confirmation was followed by a spotting assay, finally yielding 13 TAM-sensitive genes under the drug-induced haploinsufficient condition. For these 13 TAM-sensitive genes, we conducted a comparative analysis of their Gene Ontology (GO) 'biological process' terms identified from other genome-wide screenings of the budding yeast deletion library and the MCF7 breast cancer cell line. Several TAM-sensitive genes overlapped between the yeast strains and MCF7 in GO terms including 'cell cycle' (cdc2, rik1, pas1, and leo1), 'signaling' (sck2, oga1, and cki3), and 'vesicle-mediated transport' (SPCC126.08c, vps54, sec72, and tvp15), suggesting their roles in the ER-independent cytotoxic effects of TAM. We recently reported that the cki3 gene with the 'signaling' GO term was related to the ER-independent antifungal action mechanisms of TAM in yeast. In this study, we report that haploinsufficiency of the essential vps54 gene, which encodes the GARP complex subunit, significantly aggravated TAM sensitivity and led to an enlarged vesicle structure in comparison with the SP286 control strain. These results strongly suggest that the vesicle-mediated transport process might be another action mechanism of the ER-independent antifungal or cytotoxic effects of TAM.

• 약학회지
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• 제38권1호
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• pp.6-11
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• 1994

The MeOH extract of the fruits of Melia toosendan was selected for futher study by its cytotoxicity and effect on the human breast cancer cell line, MCF-7. The active principle obtained by activity guided fractionation followed by purification gave rise to a needle crystal. The structure was deduced by employing NMR and was determined to be identical with 28-deacetyl sendanin by comparison with published data. This compound induced morphological change of MCF-7 to be rounded with tubule at concentrations between $50\;{\mu}g/ml$ and $0.025\;{\mu}g/ml$. This compound, however, showed strong cytotoxic effect on Hepalclc7 and HepG2, and their $GI_{50}$ on the hepatoma cell lines were $0.238\;{\mu}g/ml$ and $0.805\;{\mu}g/ml$, respectively. Its effect on lymphocyte of mouse was stronger than hepatoma cell lines, and their $ED_{50}$ of polyclonal antibody response was $0.011\;{\mu}g/ml$, and $ED_{50}$ of cell viability was $0.039\;{\mu}g/ml$.

• Mass Spectrometry Letters
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• 제11권2호
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• pp.36-40
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• 2020

Untargeted metabolomics is a useful tool for drug development focusing on novel chemotherapeutic and chemopreventative agents against cancer cells. In recent years, quadrupole time of flight liquid chromatography-mass spectrometry (Q-TOF LC/MS)-based untargeted metabolomic approaches have gained importance to evaluate the effect of these agents at the molecular level. The researchers working on cell culture studies still do not apply standardized methodologies on sample preparation for untargeted metabolomics approaches. In this study, the rough and wet lysis techniques performed on MCF-7 breast cancer cells were compared with each other via the Q-TOF LC/MS-based metabolomic approach. The C18 and hydrophilic interaction liquid chromatography (HILIC) columns were used for the separation of the metabolites in MCF-7 cell lysates. 505 peaks were detected through the HILIC column and 551 peaks were found through the C18 column for the wet lysis technique. This situation supported by the base peak chromatograms showed that the wet lysis technique allowed us to extract higher number of non-polar metabolites. Almost equal number of metabolites was found for the C18 and HILIC columns (697 peaks for the HILIC column and 695 peaks for the C18 column) when the rough lysis technique was used. However, the intensities of polar metabolites were higher for the rough lysis technique on base peak chromatograms for both the HILIC and C18 columns. Although cell lysis technique, which is the first step in the sample preparation for cell culture studies, does not cause dramatic differences in the number of the detected metabolite peaks, it affects the polar and non-polar metabolite ratio significantly. Therefore, it must be considered carefully especially for in vitro drug development studies.

• 한국자원식물학회지
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• 제33권6호
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• pp.551-557
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• 2020

In this study, we were performed to elucidate the antioxidant and anticancer activity by leaves extracts from Acer tegmentosum (AT-L). In DPPH, ABTS radical scavenging activity, the AT-L revealed the high scavenging activity. Especially, the AT-L measured the highest ABTS radical scavenging activity, which is higher than ascorbic acid. The types of human cancer cells for evaluating the anticancer activity were colorectal cancer (SW480), prostate cancer (PC-3), breast cancer (MCF-7), pancreatic cancer (AsPC-1), lung cancer (A549) and liver cancer (HepG2). Human cancer cell viability was measured using MTT assay. Treatment of the AT-L decreased the cell viability and induced apoptosis in SW480 cells. These results suggest that extracts of the AT-L can be used as supplementary material for developing the natural antioxidant and anticancer drug for human cancer cells.

• 한국식품영양과학회지
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• 제29권2호
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• pp.322-328
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• 2000

This study was performed to determine the antimutagenic and cytotoxic effect of the Phellinus linteus methanol extract on Salmonella typhimurium TA98, TA100 and human cancer cell lines. In the Ames test, methanol extract of P. linteus alone did not exhibit any mutagenicity but showed substantial inhibitory effects against mutation induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG), 4-nitroquinoline-nitroquinoline-1-oxide(4NQO), 3-amino-1,4-dimethyl-5H-pyrdo[4,3-blindol(Trp-P-1) and benzo(α)pyrene(B(α)P). The methanol extracts of P. linteus(200㎍/plate) showed approximately 78.3%, 78.7% and 88.1% inhibitory effect on the mutagenesis induced by 4NQO, Trp-P-1 and B(α)P. The anticancer effects of P. linteus extract against human breast adenocarcinoma(MCF7), human lung carcinoma (A549), human fibrosarcoma (HT1080), human hepatocelular carcinoma (Hep3B) and human epitheloid carcinoma (HeLa) were investigated. The treatment of 1mg/mL P. linteus extracts had the highest cytotoxicity against MCF7 (92.0%), followed by Hep3B (84.9%), A549 (84.2%) and HT1080 (82.9%). In contrast 1mg/mL treatment of P. linteus extracts had only 10∼40% cytotoxicity on normal human liver cell (WRL68).

• Archives of Pharmacal Research
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• 제24권3호
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• pp.211-213
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• 2001

A coumestan derivative, psoralidin (1) was found to be a cytotoxic principle of the seeds of Psoralea corylifolia L (Leguminosae) with the IC_{50}$ values of 0.3 and 0.4 ug/ml against the HT-29 (colon) and MCF-7 (breast) human cancer cell lines, respectively. A coumarin, angelicin (2) was also isolated as a marginally cytotoxic agent along with an inactive compound, psoralene (3) from the plant. The isolates 1-3 were not active against the A54l(lung) and HepG2 (liver hepatoma) cancer cell lines.

• Molecules and Cells
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• 제45권6호
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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.

• Toxicological Research
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• 제21권1호
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• pp.31-37
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• 2005

The inhibitory activity against bisphenol-A (BPA), one of well-known endocrine disrupters was examined with the water extracts prepared from the Stem Bark of Syringa velutina (SBS). In this study, we have investigated the effect of SBS on the toxicity caused by BPA in human breast cancer cell line, MCF-7 cells and immature Sprague-Dawley rats. In the estrogen receptor-mediated proliferation assay using MCF-7 cells, BPA (16 ng/ml) induced the cell proliferation, but the water extract of SBS inhibited BPA-induced cell proliferation in a dose-dependent manner. These results are associated with PARP degradation and specific cleavage of anti-apoptotic protein Bcl-2 of apoptotic regulatory factors. Additionally, the BPA (400 mg/100 g) significantly induced the increase of the uterine and virginal weights, while SBS (50 mg/100 g) showed the inhibitory action against BPA, i.e. caused the increase of estrogen-related organ weights in immature rat uterotrophic assay. Taken together, the present data suggest that SBS may have anti-toxicity activities against BPA in vitro and in vivo systems. SBS may be capable of inhibiting adverse effects of BPA such as reproductive disorder.

• 한국자원식물학회지
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• 제29권3호
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• pp.297-304
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• 2016

The seed of safflower (Carthamus tinctorius L) has been reported to suppress human cancer cell proliferation. However, the mechanisms by which safflower seed inhibits cancer cell proliferation have remained nuclear. In this study, the inhibitory effect of the safflower seed (SS) on the proliferation of human colorectal cancer cells and the potential mechanism of action were examined. SS inhibited markedly the proliferation of human colorectal cancer cells (HCT116, SW480, LoVo and HT-29). In addition, SS suppressed the proliferation of human breast cancer cells (MDA-MB-231 and MCF-7). SS treatment decreased cyclin D1 protein level in human colorectal cancer cells and breast cancer cells. But, SS-mediated downregulated mRNA level of cyclin D1 was not observed. Inhibition of proteasomal degradation by MG132 attenuated cyclin D1 downregulation by SS and the half-life of cyclin D1 was decreased in SS-treated cells. In addition, SS increased cyclin D1 phosphorylation at threonine-286 and a point mutation of threonine-286 to alanine attenuated SS-mediated cyclin D1 degradation. Inhibition of ERK1/2 by PD98059 suppressed cyclin D1 phosphorylation and downregulation of cyclin D1 by SS. In conclusion, SS has anti-proliferative activity by inducing cyclin D1 proteasomal degradation through ERK1/2-dependent threonine-286 phosphorylation of cyclin D1. These findings suggest that possibly its extract could be used for treating colorectal cancer.