• Biomolecules & Therapeutics
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• 제26권5호
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• pp.494-502
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• 2018

Breast cancer is currently the most prevalent cancer in women, and its incidence increases every year. Azole antifungal drugs were recently found to have antitumor efficacy in several cancer types. They contain an imidazole (clotrimazole and ketoconazole) or a triazole (fluconazole and itraconazole) ring. Using human breast adenocarcinoma cells (MCF-7 and MDA-MB-231), we evaluated the effects of azole drugs on cell proliferation, apoptosis, cell cycle, migration, and invasion, and investigated the underlying mechanisms. Clotrimazole and ketoconazole inhibited the proliferation of both cell lines while fluconazole and itraconazole did not. In addition, clotrimazole and ketoconazole inhibited the motility of MDA-MB-231 cells and induced $G_1$-phase arrest in MCF-7 and MDA-MB-231 cells, as determined by cell cycle analysis and immunoblot data. Moreover, Transwell invasion and gelatin zymography assays revealed that clotrimazole and ketoconazole suppressed invasiveness through the inhibition of matrix metalloproteinase 9 in MDA-MB-231 cells, although no significant changes in invasiveness were observed in MCF-7 cells. There were no significant changes in any of the observed parameters with fluconazole or itraconazole treatment in either breast cancer cell line. Taken together, imidazole antifungal drugs showed strong antitumor activity in breast cancer cells through induction of apoptosis and $G_1$ arrest in both MCF-7 and MDA-MB-231 cells and suppression of invasiveness via matrix metalloproteinase 9 inhibition in MDA-MB-231 cells. Imidazole drugs have well-established pharmacokinetic profiles and known toxicity, which can make these generic drugs strong candidates for repositioning as antitumor therapies.

• 한국환경성돌연변이발암원학회지
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• 제26권1호
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• pp.12-19
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• 2006

Cadmium, a human carcinogen, can induce toxicity in various cell lines and organs. Despite extensive research, the mechanisms of cadmium-induced cell toxicity and estrogenic potential in human are not clear. This study was performed to investigate cadmium-induced toxicity on human breast cancer cells: MCF-7 cells, an estrogen receptor (ER) positive breast cancer cells, and MDA-MB-231 cells, an ER negative breast cancer cells. MCF-7 cells was proved to be more sensitive than the other cell lines (IC50 = $50\;{\mu}M$ at MCF-7 cells and $120{\mu}M$ at MDA-MB-231). The expression of JNK and AP-1 transcription factors such as c-Jun and c-Fos dependent transcription were increased by cadmium treatment. Inhibition of ER activation by ER antagonist (tamoxifen or ICI 182,780) significantly recovered the viablity and inhibited apoptotic cell death. This suggested that cadmium-induced cell death in ER (+) cells was mediated by JNK/AP-1 pathway and this pathway was more stimulated by ER activated by cadmium. Co-treatment of antioxidants such as selenium (Se), butylated hydroxyanisole (BHA), glutathione (GSH), or N-acetyl-L-cysteine (NAC) recovered the cadmium-induced cell death in MCF-7 cells. Cadmium-induced lipid peroxidation was decreased by GSH, NAC, or BHA in MCF-7 cells. The expression of SOD protein was decreased by cadmium ($100{\mu}M$) but recovered by GSH, NAC, BHA, or Se. Our data showed that the cadmium-induced cell toxicity in human breast cancer cells could be protected by the antioxidants (Se, BHA, NAC, GSH, or NAC) and ER antagonist (tamoxifen or ICI 182,780). Therefore, toxicity of cadmium in breast cancer were mediated by oxidative stress and $ER{\alpha}$.

• 동아시아식생활학회지
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• 제17권1호
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• pp.43-50
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• 2007

This study investigated the effects of mycelia of Lentinus edodes mushroom-cultured Glycyrrihiza radix(LMG) on cancer cell lines and sarcoma 180(S-180), as well as on human mast cells. In an anti-cancer tests using Hep3B(hepatic cancer cell), MCF-7(breast cancer), and HeLa(uterine cancer) cells, LMG extract exhibited greater anti-proliferation effects than Glycyrrihiza glabra(GG) extract. LMG extract multiplication restraining effects were 60% that of ethanol at 3 mg/mL extract also displayed tumor suppressive effects in mice injected with S-180 cells. The growth-inhibition rates against tumor cells were 56% for LMG and 37% for GG. When LMG was added to human mast cells, the Intensity of RT-PCR products using primers($FC{\varepsilon}RI\;c-kit$) decreased. significantly compared with that of control. These results suggest that Lentinus edodes Mushroom-Cultured Glycyrrhiza glabra has an anti-proliferation effects against cancer cell lines(Hep3B, MCF-7 and HeLa) and S-180 tumors and will be also beneficial in treating allergic reactions.

• Advances in Traditional Medicine
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• 제5권1호
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• pp.21-28
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• 2005

The leaf extracts of Araucaria bidwillii Hook. (Araucariaceae) were evaluated for their cytotoxic effect in various human cancer cell lines. Preliminary investigation by brine shrimp lethality assay indicated that $LC_{50}$ value of various successive extracts were found to be less than $1000\;{\mu}g/ml$, where the ethyl acetate extract showed maximum activity of less than $100\;{\mu}g/ml$. Further cytotoxic evaluation of various leaf extracts of Araucaria bidwilli Hook was carried out in four different human cancer cell lines-acute myeloblastic leukemia (HL-60), chronic myelogenic leukemia (K-562), breast adenocarcinoma (MCF-7) and cervical epithelial carcinoma (HeLa). Cytotoxicity was assessed by trypan blue dye exclusion method and 3-(4,5-dimethyl thiazole-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction assay. From the present investigation it was found that the ethyl acetate and methanol extract of Araucaria bidwilli Hook was found to be more effective in leukemic cell lines and was less effective in MCF-7 and HeLa. The $IC_{50}$ value of the ethyl acetate extract in leukemic cell lines was found to be $28.18\;and\;34.64\;{\mu}g/ml$ and methanol extract was found to be $33.11\;&\;39.81\;{\mu}g/ml$. It can be concluded that various extract from the leaves of Araucaria bidwillii Hook. posses cytotoxic activity tested in brine shrimps and various human carcinoma cell lines.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3223-3228
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• 2016

Reports indicate that 15-deoxy-delta-12,14-prostaglandin-J2 (15d-PGJ2) has anticancer activities, but its mechanisms of action have yet to be fully elucidated. We therefore investigated the effects of 15d-PGJ2 on the human breast cancer cell lines, MCF-7 (estrogen receptor $ER{\alpha}+/ER{\beta}+$) and MDA-MB-231 ($ER{\alpha}-/ER{\beta}+$). Cellular proliferation and cytotoxicity were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays while apoptosis was determined by fluorescence microscopy and flow cytometry using annexin V-propidium iodide (PI) staining. ER expression was determined by Western blotting. Intracellular calcium was stained with Fluo-4 AM while intracellular caspase activities were detected with Caspase-$FLICA(R)$ and measured by flow cytometry. We showed that 15d-PGJ2 caused a significant increase in apoptosis in MCF-7 and MDA-MB-231 cells. $ER{\alpha}$ protein expression was reduced in treated MCF-7 cells but pre-incubation with the $ER{\alpha}$ inhibitor' ICI 182 780' did not affect the percentage of apoptotic cells. The expression of $ER{\beta}$ was unchanged in both cell lines. In addition, 15d-PGJ2 increased intracellular calcium ($Ca^{2+}$) staining and caspase 8, 9 and 3/7 activities. We therefore conclude that 15d-PGJ2 induces caspase-dependent apoptosis that is associated with an influx of intracellular $Ca^{2+}$ with no involvement of ER signaling.

• Bulletin of the Korean Chemical Society
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• 제34권5호
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• pp.1349-1354
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• 2013

Twenty two new 5-fluorouracil (5-FU) derivatives, 2-butoxy-4-substituted 5-fluoropyrimidines, were synthesized and characterized by IR, $^1H$ NMR, MS, HRMS. All compounds were preliminarily evaluated by MTT assay on human liver BEL-7402 cancer cell line in vitro. Ten compounds were selected to test their cytotoxic activity against A549, HL-60 and MCF-7 cancer cell lines in vitro. These compounds were more sensitive to BEL-7402 than other cell lines, particularly, cytotoxic activity of compounds 6b, 6d-f, 6p, 6s-u were in sub-micromolar scale. The highest cytotoxic potency against A549, HL-60 and MCF-7 was shown by 2-butoxy-4-chloro-5-fluoropyrimidine (5) with $IC_{50}$ values of 0.10, 1.66 and $0.59{\mu}M$, respectively. Compounds 6d and 6e were effective against MCF-7 with $IC_{50}$ $9.73{\mu}M$ and HL-60 with $IC_{50}$ $8.83{\mu}M$, respectively.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2003년도 학술발표대회 발표논문초록집
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• pp.94-94
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• 2003

Endocrine disrupters (EDs) are exogenous chemicals that interfere with the production, releasing, metabolism, excretion, binding of natural hormones, and whole endocrine systems. EDs are very dangerous since they are extremely stable, not easily degraded, and accumulated in fat and tissue. 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is known as the most toxic EDs. Therefore, this study was conducted to investigate the effects of TCDD on proliferation of human breast cancer (MCF-7) and endometrial adenocarcinoma (Hec-1B) cells. 10, 100, and 1000 nM of TCDD were treated with steroid free condition. Viable cell counting, MTT, and BrdU assay was performed to investigate cell proliferation. Apoptosis was investigated using DNA laddering. Although, DNA fragmentation as the evidence of apoptosis was not detected, all of these cell lines showed restricted proliferation at 48 hrs after 100 and 1000 nM TCDD treatments. Recently, it has been reported that the expression of transforming growth factor $\beta$s (TGF-$\beta$s) are increased in TCDD treatment and also involved in regulation of cell cycle. Therefore, these results were considered that the decreased cell prolifcration by TCDD is related to the expression of TGF-$\beta$s.

• 대한화학회지
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• 제63권2호
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• pp.85-93
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• 2019

A panel of chalcone-sulphonamide hybrids has been designed by tethering appropriate sulphonamide scaffold with substituted chalcones as a multi-target drug for anticancer screening. Chalcones were prepared by Claisen-Schmidt condensation reaction of a substituted aldehyde with para aminoacetophenone. All the synthesized compounds were evaluated against selected five cancer cell lines, MCF-7 (Breast cancer), DU-145 (Human prostate Carcinoma), HCT-15 (Colon cancer), NCIH-522 (stage 2, adenocarcinoma; non-small cell lung cancer) and HT-3 (Human cervical cancer). Most of the synthesized chalcone-sulphonamide hybrids showed amended cytotoxic activity against various cancer cell lines which may be attributed to the linkage of sulphonamide with chalcone skeleton. The synthesized compounds were characterized by FT-IR, $^1H$ NMR, $^{13}C$ NMR and HR-LCMS and spectral study assert the structures of synthesized sulphonamide-chalcone hybrids.

• Journal of Microbiology and Biotechnology
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• 제16권9호
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• pp.1405-1409
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• 2006

Polysaccharides from the starfish Asterina pectinifera were assessed in vitro for their chemopreventive potential in human breast cancer. The polysaccharides from A. pectinifera inhibited cell proliferation in the estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) human breast carcinoma cell lines. In addition, the polysaccharides were found to be an inhibitor of cytochrome P450 1A1-mediated ethoxyresorufin O-deethylase activity, and caused a dose-dependent inhibition of aromatase activity in microsomes isolated from a human placenta. There was a significant reduction in the ornithine decarboxylase activity to 30.7% of the control in the polysaccharide-treated MCF-7 breast cancer cells. Therefore, the polysaccharides from A. pectinifera merit further investigation with respect to breast cancer chemoprevention.

• Journal of Nutrition and Health
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• 제40권2호
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• pp.147-153
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• 2007

In this study, we investigated the anticancer activity of the fin of Thunnus Thynnus (TT). TT was extracted with methanol (TTM), and then further fractionated into four subfractions by using solvent partition method, affording hexane (TTMH), methanol (TTMM), butanol (TTMB) and aquous (TTMA) soluble fractions. We determined the cytotoxicity of these four fractions in four kind of cancer cell lines, such as HepG2, MCF-7, B16-F10 and HT29 by MTT assay. The TTMM showed the strongest cytotoxic effect at the concentration of 150 ${\mu}g/mL$, displaying 95% on the HepG2 cell lines and 82% on MCF-7 cell line. The morphological changes such as membrane shirinking and blebbing of cells were also observed by TTMM treatment in HT29 cell. In addition, we observed that quinone reductase (QR) activity was elevated by only TTMM and TTMH treatments in HepG2 cell. QR activity was increased to around 2.0 and 1.8 times in TTMM and TTMH treated HepG2 cell at 100 ${\mu}g/mL$, respectively, compared to that in control. Although further studies are needed, the present work could suggest that the fin of TT has a potential to be usable as a chemopreventive agent against cancer.