• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.2087-2092
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• 2015

Nowadays herbal-derived medicines are attracting attention as new sources of drugs with few side effects. Silibinin is a flavonoid compound with chemotheraputic effects on different cancers such as examples in the prostate, lung, colon and breast. In the present study, the cytotoxic effects of silibinin on MCF7 breast cancer cells were investigated. Apoptosis was determined by flow cytometry and the impact of silibinin on the expression of pivotal genes including Bak, P53, P21, BRCA1, BCL-X1 and ATM was analyzed. Treatment for 24h had a significant dose-dependent inhibitory effect on cell growth (p<0.05) with dose- and time- dependent induction of apoptosis (p<0.05). In addition, there were significant increases in BRCA1, ATM, Bak and Bcl-XL gene expression at the mRNA level with different concentrations of silibinin for 24 or 48 h (p<0.05). Taken together, the results suggest that silibinin inhibits the proliferation and induces apoptosis of MCF-7 cells by down-regulating Bak, P53, P21, BRCA1, BCL-Xl and thus may be considered as an effective adjuvant drug to produce a better chemopreventive response for the cancer therapy.

• Journal of Microbiology and Biotechnology
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• v.30 no.6
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• pp.893-902
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• 2020

Propolis is a resinous substance that is collected by Apis mellifera from plant sources and is used in traditional medicine. To study the phytochemical constituents and apoptotic potential of Jordanian propolis extract against different cancer cell lines, propolis was extracted using methanol, hexane, and ethyl acetate and was fractionated using chromatographic methods. Cytotoxicity was assessed using MTT and LDH assays. The apoptotic potential was investigated using florescence microscopy, multicaspase assay, Annexin-V and dead cell assay, and cell cycle assay. The phytochemical constituents were analyzed using GC-MS. The methanol extract of propolis exhibited cytotoxic potential against all cell lines tested. The IC₅₀ values of the methanol extract were 47.4, 77.8, 91.2, and 145.0 ㎍/ml for HepG2, LoVo, MDAMB231, and MCF7 cell lines, respectively. The IC₅₀ values of the F1 fraction were 31.6 (MDAMB231), 38.9 (HepG2), 36.7 (LoVo) and 75.5 (MCF7) ㎍/ml. On further purification using thin-layer chromatography, the IC₅₀ values of the F1-3 fraction were found to be 84.31(HepG2), 79.2 (MCF7), 70.4 (LoVo), and 68.9 (MDAMB231) ㎍/ml, respectively. The anticancer potential of the F1 fraction was confirmed through the induction of apoptosis and cell cycle arrest at the G0/G1 phase. The GC-MS analysis of the F1 fraction revealed the presence of 3-methyl-4-isopropylphenol (29.44%) as a major constituent. These findings indicate the potential of propolis extract as a cancer therapy. However, further investigation is required to assess the acute and subacute toxicity of the most active fraction.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.3
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• pp.385-389
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• 2010

Butein(3,4,2',4-tetrahydroxychalcone) has been reported anticancer effects in several cancer type, which is prostate, bladder cancer but breast cancer is not. This study was to investigate the antiproliferative effects by butein(3,4,2',4-tetrahydroxychalcone) in MCF-7 human breast carcinoma cells. We invastigated the effects of dose-dependently cell growth inhibition by butein, which could be proved by WST-1 assay. Also, flow cytometry analysis was butein increase percentage of subG1 phase. As well as, butein induces apoptosis through the expression of caspase-8,-3 and poly(ADP-ribose) polymerase(PARP) activation but not in DMSO treated cells. Taken together, this results suggest that butein induced MCF-7 apoptosis through extrinsic pathway and thus may have potential tumor suppressor in breast cancer.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.455-462
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• 2018

Background: Ginsenoside Rh2 has been known to enhance the activity of immune cells, as well as to inhibit the growth of tumor cells. Although the repertoire of genes regulated by Rh2 is well-known in many cancer cells, the epigenetic regulation has yet to be determined, especially for comprehensive approaches to detect methylation changes. Methods: The effect of Rh2 on genome-wide DNA methylation changes in breast cancer cells was examined by treating cultured MCF-7 with Rh2. Pyrosequencing analysis was carried out to measure the methylation level of a global methylation marker, LINE1. Genome-wide methylation analysis was carried out to identify epigenetically regulated genes and to elucidate the most prominent signaling pathway affected by Rh2. Apoptosis and proliferation were monitored to examine the cellular effect of Rh2. Results: LINE1 showed induction of hypomethylation at specific CpGs by 1.6-9.1% (p < 0.05). Genome-wide methylation analysis identified the "cell-mediated immune response"-related pathway as the top network. Cell proliferation of MCF-7 was retarded by Rh2 in a dose-dependent manner. Hypermethylated genes such as CASP1, INSL5, and OR52A1 showed downregulation in the Rh2-treated MCF-7, while hypomethylated genes such as CLINT1, ST3GAL4, and C1orf198 showed upregulation. Notably, a higher survival rate was associated with lower expression of INSL5 and OR52A1 in breast cancer patients, while with higher expression of CLINT1. Conclusion: The results indicate that Rh2 induces epigenetic methylation changes in genes involved in immune response and tumorigenesis, thereby contributing to enhanced immunogenicity and inhibiting the growth of cancer cells.

• Environmental Mutagens and Carcinogens
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• v.22 no.4
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• pp.312-318
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• 2002

Dioxin represents a group of halogenated aromatic hydrocarbons of which 2,3,7,8-tetrachlorod-ibenzo-p-dioxin (TCDD) is well known for its extremely toxic properties as well as ubiquitous presence in our environment and ecosystems. In order to better assess the carcinogenic mechanism of dioxin, we should utilize the reliable biomarkers that can precisely and correctly reflect multi-stage carcinogenesis. When MCF10A cells were exposed to TCDD (10 nM), expression of both CYP1A1 and CYP1B1 was induced in a time-related manner. The expression as well as activity of ornithine decarboxylase was transiently induced by TCDD treatment. In contrast, the induction of COX-2 that is implicated in carcinogenesis as well as inflammation, was not induced by TCDD. In another study, gap-junctional intercellular communication (GJIC) was attenuated by TCDD treatment as revealed by the dye-transfer assay. Based on these findings, TCDD has both tumor initiating and promoting potential in human breast epithelial cells in culture. Also, treatment of MCF10A cells with the carcinogen 7,12-dimethylbenz[a]anthracene plus TCDD resulted in malignant cell transformation as revealed by increased anchorage-independent growth of exposed cells. Additional studies may be necessary to assess the effects of TCDD on multi-stage carcinogenesis in vivo.

• Journal of Microbiology and Biotechnology
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• v.30 no.2
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• pp.279-286
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• 2020

A novel compound named 'kanakugiol' was recently isolated from Lindera erythrocarpa and showed free radical-scavenging and antifungal activities. However, the details of the anti-cancer effect of kanakugiol on breast cancer cells remain unclear. We investigated the effect of kanakugiol on the growth of MCF-7 human breast cancer cells. Kanakugiol affected cell cycle progression, and decreased cell viability in MCF-7 cells in a dose-dependent manner. It also enhanced PARP cleavage (50 kDa), whereas DNA laddering was not induced. FACS analysis with annexin V-FITC/PI staining showed necrosis induction in kanakugiol-treated cells. Caspase-9 cleavage was also induced. Expression of death receptors was not altered. However, Bcl-2 expression was suppressed, and mitochondrial membrane potential collapsed, indicating limited apoptosis induction by kanakugiol. Immunofluorescence analysis using α-tubulin staining revealed mitotic exit without cytokinesis (4N cells with two nuclei) due to kanakugiol treatment, suggesting that mitotic catastrophe may have been induced via microtubule destabilization. Furthermore, cell cycle analysis results also indicated mitotic catastrophe after cell cycle arrest in MCF-7 cells due to kanakugiol treatment. These findings suggest that kanakugiol inhibits cell proliferation and promotes cell death by inducing mitotic catastrophe after cell cycle arrest. Thus, kanakugiol shows potential for use as a drug in the treatment of human breast cancer.

• Environmental Mutagens and Carcinogens
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• v.19 no.1
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• pp.56-62
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• 1999

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) has been considered to be as one of major antioxidants present in grapes responsible for beneficial effects of red wine consumption on coronary heart disease. This triphenolic stilbene has been suggested as a potential cancer chemopreventive agent based on its striking inhiitory effects on diverse cellular events associated with tumor initiation, promotion, and progression. The compound has strong antioxidative and anti-inflammatory activities which amy contribute to its chemopreventive/chemoprotective properties. In the present work, we have found that resveratrol reduces viability and DNA synthesis capability of cultured human promyelocytic leukemia (HL-60) cells. Likewise, the viability of human breast cancer cell line, MCF-7 was reduced by resveratrol treatment. The growth inhibitory and antiproliferative properties of resveratrol appear to be associated with its induction of apoptotic cell death as determined by morphological and ultrastructural changes, agarose gel electrphoretic analysis of internucleosomal DNA fragmentation, and in situ terminal end-labeling of fragmented DNA (TUNEL). This compound also inhibited the phorbol ester-induced expression of cyclooxygenase-2 (COX-2) protein in immortalized human mammary epithelial MCF-10A cells. These results suggest that resveratrol has the promising cancer therapeutic/chemopreventive potential.

• Natural Product Sciences
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• v.22 no.2
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• pp.122-128
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• 2016

This paper reports in vitro cytotoxic, anti-inflammatory and adipocyte diffentiation with adipogenic effects of coumarins inophyllum D (1) and calanone (2), and a chromanone carboxylic acid namely isocordato-oblongic acid (3) isolated from Calophyllum symingtonianum as well as a biflavonoid morelloflavone (4) isolated from Garcinia prainiana on MCF-7 breast adenocarcinoma RAW 264.7 macrophages and 3T3-L1 preadipocytes cells, respectively. The cytotoxicity study on MCF-7 cell was conducted by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Meanwhile, the study of anti-inflammatory effects in RAW 264.7 macrophages and adipogenic effects on 3T3-L1 pre-adipocytes were conducted through nitrite determination assay and induction of adipocyte differentiation, respectively. In the cytotoxicity study, inophyllum D (1) was the only compounds that exhibited significant cytotoxic effect against MCF-7 cell with $IC_{50}$ of $84{\mu}g/mL$. Further, all by inhibiting the compounds have shown anti-inflammatory effects in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages of nitrite concentration with production. In addition, the compounds also exhibited adipogenic effects on 3T3-L1 pre-adipocytes by stimulating lipid formation. Thus, this study may provide significant input in discovery of the potential effects cytotoxic, anti-inflammatory and adipogenic agents.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.1
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• pp.143-148
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• 2002

We investigated the cytotoxicity effects of Lycii fructus (LF) on HePG2, MCF7 and C6 cell lines by the MTT assay. We extracted the methanol (LFM) and fractionated to five partition layers. Among partition layers, the ethylether partition layer (LFMEE) was showed the strongest cytotoxic effects on all cancer cell lines. The hexane partition layer (LFMH) also was showed significant cytotoxic activities on Hela and MCF-7 cell lines. We also determined the induction of intracellular quinone reductase (QR) activity on HepG2 cells. Among various partition layers of Lycii fructus; LFMH was showed the most effective such induced effect such as 1.85 to the control value of 1.0. And we also determined the enhancement of anticarcinogenic effect by combination of Lycii fructus with vitamin C on all cell lines. These results suggest that potentially useful anticarcinegenic chemicals could be isolated from LFMEE and LFMH of the Lycii frutus and also we found the enhanced effect by the combination of various partition layers of LFM with vitamin C.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1757-1762
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• 2014

Development of drugs from natural products has been undergoing a gradual evoluation. Many plant derived compounds have excellent therapeutic potential against various human ailments. They are important sources especially for anticancer agents. A number of promising new agents are in clinical development based on their selective molecular targets in the field of oncology. D-pinitol is a naturally occurring compound derived from soy which has significant pharmacological activitites. Therefore we selected D-pinitol in order to evaluate apoptotic potential in the MCF-7 cell line. Human breast cancer cells were treated with different concentrations of D-pinitol and cytotoxicity was measured by MTT and LDH assays. The mechanism of apoptosis was studied with reference to expression of p53, Bcl-2, Bax and NF-kB proteins. The results revealed that D-pinitol significantly inhibited the proliferation of MCF-7 cells in a concentration-dependent manner, while upregulating the expression of p53, Bax and down regulating Bcl-2 and NF-kB. Thus the results obtained in this study clearly vindicated that D-pinitol induces apotosis in MCF-7 cells through regulation of proteins of pro- and anti-apoptotic cascades.