• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.10a
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• pp.89-89
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• 2019

Several studies report the anticancer effect of Glycyrrhiza glabra (G. glabra), Glycyrrhiza uralensis (G. uralensis) and their compounds. However, the anticancer effect of Glycyrrhiza cultivar roots are limited. In this study, we compared the anticancer effect of Glycyrrhiza cultivar (Wongam and Shinwongam) extracts with G. glabra and G. uralensis extracts in breast cancer cell lines. Freeze dried Glycyrrhiza root extracts were dissolved in cell culture media at 2 mg/mL and filtered by $0.2{\mu}m$ filter. Glycyrrhiza root extracts were serially diluted at the concentrations of $10{\mu}g/mL$, $100{\mu}g/mL$, $200{\mu}g/mL$, $400{\mu}g/mL$, $800{\mu}g/mL$, $1000{\mu}g/mL$ and $2000{\mu}g/mL$. MCF-7 and MDA-MB-231 breast cancer cells were treated with different concentrations of Glycyrrhiza root extracts and the cell viability was measured using MTT assay. In MCF-7 cells, G. glabra showed no significant difference with Wongam and showed significant difference with Shinwongam at $1000{\mu}g/mL$ (G. glabra 101.2% and Shinwongam 82.68%) and $2000{\mu}g/mL$ (G. glabra 83.07% and Shinwongam 54.05%). G. uralensis showed significant difference with Wongam at $2000{\mu}g/mL$ (G. uralensis 66.48% and Wongam 95.02%) and showed no significant difference with Shinwongam. In MDA-MB-231 cells, G. glabra showed no significant difference with both Wongam and Shinwongam. G. uralensis showed significant difference with Wongam at $2000{\mu}g/mL$ (G. uralensis 72.59% and Wongam 93.47%) and showed no significant difference with Shinwongam. In conclusion, the current study demonstrated that G, glabra and G. uralensis compared with Wongam, and Shinwongam at low concentrations ($10{\mu}g/mL{\sim}800{\mu}g/mL$) display similar cytotoxic potency.

• BMB Reports
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• v.52 no.6
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• pp.379-384
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• 2019

Epithelial-mesenchymal transition (EMT) is widely-considered to be a modulating factor of anoikis and cancer metastasis. We found that, in MDA-MB-231 cells, TP53I11 (tumor protein P53 inducible protein 11) suppressed EMT and migration in vitro, and inhibited metastasis in vivo. Our findings showed that hypoxic treatment upregulated the expression of $HIF1{\alpha}$, but reduced TP53I11 protein levels and TP53I11 overexpression reduced $HIF1{\alpha}$ expression under normal culture and hypoxicconditions, and in xenografts of MDA-MB-231 cells. Considering $HIF1{\alpha}$ is a master regulator of the hypoxic response and that hypoxia is a crucial trigger of cancer metastasis, our study suggests that TP53I11 may suppress EMT and metastasis by reducing $HIF1{\alpha}$ protein levels in breast cancer cells.

• CELLMED
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• v.11 no.3
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• pp.16.1-16.7
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• 2021

Cancer is an abnormal growth of cells in body which leads to death. These cells are born due to imbalance in cell proliferation mechanism. In 2018, WHO released new statistics on cancer incidence, mortality, and prevalence worldwide i.e., GLOBOCAN 2018 estimates for 28 types of cancer in which more prevalence of cervix and breast cancer. According to survey, in India about 7.8 million cancer deaths and 11.5 million new cases arise in 2018, which will increase to 19.3 million new cases per year by 2025. Though breast cancer as such is not explained anywhere in Ayurvedic compendia, correlations can be done with the Stana Arbuda. Ayurveda, the ancient system of medicine came into existence 1000's of years ago with an objective of maintaining the health of people and treating diseases. Many herbs used in Ayurveda have been screened for activity against cancer and in-vitro and in-vivo studies have given promising leads. The plant, called as "Mother of Medicine", Haritaki has been extensively studied for its various ailments because of its extraordinary healing potency. Haritaki (Terminalia chebula Retz.), Family: Combretaceae have a great therapeutic value and is widely distributed in India. Dried fruit of Terminalia chebula contains high quantities phenolic compounds consist of ellagic acid, gallic acid and chebulic acid. The fruit extract of T. chebula is having different biological properties like anticancer, antioxidant, hepatic and renal protective activities etc. In this study, we focus on the use of CO₂ extract of Terminalia chebula, on the breast cancer cell line MDA-MB-231. All tests proved that CO₂ extract of Terminalia chebula containing active chemical component, therefore our experiment showed the positive results for CO₂ extract of Terminalia chebula against breast cancer cell line cancer MDA-MB-231. The MTT assay results were used to evaluate the anti-cancer activity of the extract. The percentage of cell growth and cell viability were calculated from tabulated result values of MTT assay. Cell viability MTT assay also showed significant growth inhibition, at the same time statistical analysis of MTT assay also proved significant results.

• Nutrition Research and Practice
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• v.12 no.2
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• pp.129-134
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• 2018

BACKGROUND/OBJECTIVES: Although several recent studies have reported the anti-cancer effects of extracts or components of Citrus unshiu peel, which has been used for various purposes in traditional medicine, the molecular mechanisms for their effects remain unclear. In the present study, the anti-cancer activity of a water-soluble extract of C. unshiu peel (WECU) in MDA-MB-231 human breast carcinoma cells at the level of apoptosis induction was investigated. MATERIALS/METHODS: Cytotoxicity was evaluated using the MTT assay. Apoptosis was detected using DAPI staining and flow cytometry analyses. Mitochondrial membrane potential, reactive oxygen species (ROS) assay, caspase activity and Western blotting were used to confirm the basis of apoptosis. RESULTS: The results indicated that WECU-induced apoptosis was related to the activation of caspase-8, and -9, representative initiator caspases of extrinsic and intrinsic apoptosis pathways, respectively, and caspase-3 accompanied by proteolytic degradation of poly(ADP-ribose) polymerase and down-regulation of the inhibitors of apoptosis protein family members. WECU also increased the pro-apoptotic BAX to anti-apoptotic BCL-2 ratio, loss of mitochondrial membrane potential and cytochrome c release from mitochondria to cytoplasm. Furthermore, WECU provoked the generation of ROS, but the reduction of cell viability and induction of apoptosis by WECU were prevented when ROS production was blocked by antioxidant N-acetyl cysteine. CONCLUSIONS: These results suggest that WECU suppressed proliferation of MDA-MB-231 cells by activating extrinsic and intrinsic apoptosis pathways in a ROS-dependent manner.

• 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.

• Journal of Life Science
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• v.22 no.7
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• pp.964-969
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• 2012

Genistein, a predominant isoflavone, has been shown to inhibit the growth of various cancer cells in vitro and in vivo without toxicity to normal cells. In the present study, we investigated the effects of genistein on the activity and the expression of matrix metalloproteinases (MMPs) in MCF-7 and MDA-MB-231 human breast adenocarcinoma cells. Our findings showed that MMP-9 and -2 activation was significantly increased in response to 12-O-tetradecanoyl phorbol-13-acetate (TPA). However, the increased activities of MMP-9 and -2 in TPA-treated cells were concentration-dependently inhibited by treatment with genistein, and this was also correlated with a decrease in the expression of their mRNA and proteins. In addition, a matrigel invasion assay showed that genistein reduced TPA-induced invasion of MCF-7 and MDA-MB-231 cells. Although further in vivo studies are needed, these results suggest that genistein treatment may inhibit tumor cell invasion and, therefore, act as a dietary source to decrease the risk of cancer metastasis.

• Journal of Life Science
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• v.13 no.3
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• pp.314-323
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• 2003

The purpose of this study was to examine the effects of xenobiotic nuclear receptors, CAR, SXR, and PPAR${\gamma}$ on the transcriptional activity of estrogen receptor in human breast cancer cell lines and compare with those in human hepatoma cell line. Two different breast cancer cell lines, MCF-7 and MDA-MB-231 were cultured and effects of CAR, SXR, and PPAR${\gamma}$ on the ER-mediated transcriptional activation of synthetic (4ERE)-tk-luciferase reporter gene were analyzed. Consistent with the previous report, CAR significantly inhibited ER-mediated transactivation and SXR repressed modestly whereas the PPAR${\gamma}$ did not repress the ER-mediated transactivation. However, in breast cancer cells neither of the xenobiotic receptors repressed the ER-mediated transactivation. Instead, they tend to increase the transactivation depending on the cell type and xenobiotic nuclear receptors. In MCF-7, SXR but neither CAR nor PPAR${\gamma}$ slightly increased ER-mediated transactivation whereas in MDA-MB-231, CAR and PPAR${\gamma}$ but not SXR tend to increase the transactivation of the reporter gene. These results indicate that the effects of ER cross-talk by the CAR, SXR, and PPAR${\gamma}$ , are different in breast cancer cells from hepatoma cells. In conclusion, the transcriptional regulation by estrogen can involve different cross-talk interaction between estrogen receptor and xenobiotic nuclear receptors depending on the estrogen target cells.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4601-4607
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• 2014

Red rice contains pharmacological substances including phenolics, oryzanol, tocotrienol and tocopherol. Recently, red rice extract has been employed as a source of antioxidants for inhibition of tumor growth. This study was carried out to evaluate the anti-invasion effects of red rice extract fractions on cancer cells. It was found that at $100{\mu}g/ml$ of crude ethanolic extract (CEE), hexane fraction (Hex) and dichloromethane fraction (DCM) could reduce HT1080 and MDA-MB-231 cancer cell invasion. Hex and DCM revealed higher potency levels than CEE, whereas an ethyl acetate fraction (EtOAc) had no effect. Gelatin zymography revealed that Hex decreased the secretion and activity of matrix metalloproteinase-2 and -9 (MMP-2 and-9). In contrast, the DCM fraction exhibited slightly effect on MMPs secretion and had no effect on MMPs activity. Collagenase activity was significantly inhibited by the Hex and DCM fractions. High amounts of ${\gamma}$-oryzanol and ${\gamma}$-tocotrienol were found in the Hex and DCM fractions and demonstrated an anti-invasion property. On the other hand, proanthocyanidin was detected only in the CEE fraction and reduced MDA-MB-231 cells invasion property. These observations suggest that proanthocyanidin, ${\gamma}$-oryzanol and ${\gamma}$-tocotrienol in the red rice fractions might be responsible for the anti invasion activity. The red rice extract may have a potential to serve as a food-derived chemotherapeutic agent for cancer patients.

• Journal of Microbiology and Biotechnology
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• v.28 no.4
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• pp.542-550
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• 2018

Heat shock protein 90 (Hsp90) is treated as a molecular therapeutic target for the prevention and treatment of cancer. Geldanamycin (GA) was the first identified natural Hsp90 inhibitor, but hepatotoxicity has limited its clinical application. Nevertheless, a new GA analog (WK-88-1) with the non-benzoquinone skeleton, obtained from genetically engineered Streptomyces hygroscopicus, was found to have anticancer activity against two human breast cancer cell lines. WK-88-1 produced concentration-dependent inhibition of cell proliferation, cell cycle arrest, and apoptosis in estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 cell lines. Detailed analysis showed that WK-88-1 downregulated some key cell cycle molecules (CDK1 and cyclin B1) and lead to $G_2/M$ cell cycle arrest. Further studies also showed that WK-88-1 could induce human breast cancer cell apoptosis by downregulating Hsp90 client proteins (Akt, p-Akt, IKK, c-Raf, and Bcl-2), decreasing the ATP level, increasing reactive oxygen species production, and lowering the mitochondrial membrane potential. Meanwhile, we discovered that WK-88-1 significantly decreased the levels of Her-2 and $ER-{\alpha}$ in MCF-7 cells but not in MDA-MB-231 cells. In addition, WK-88-1 significantly increased caspase-3, -8, and -9 activities and the cleavage of PARP in a concentration-dependent manner (with the exception of caspase-3 and PARP in MCF-7 cells). Taken together, our preliminary results suggest that WK-88-1 has the potential to play a role in breast cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6247-6251
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• 2014

Background: The aim of the present study was to investigate the involvement of emodin on the growth of human breast cancer MCF-7 and MDA-MB-231 cells and the estrogen (E2) signal pathway in vitro. Materials and Methods: MTT assays were used to detect the effects of emodin on E2 induced proliferation of MCF-7 and MDA-MB-231 cells. Flow cytometry (FCM) was applied to determine the effect of emodin on E2-induced apoptosis of MCF-7 cells. Western blotting allowed detection of the effects of emodin on the expression of estrogen receptor ${\alpha}$, cyclin D1 and B-cell lymphoma-2 (Bcl-2), mitogen-activated protein kinases (MAPK) and phosphatidylinostiol 3-kinases (PI3K). Luciferase assays were emplyed to assess transcriptional activity of $ER{\alpha}$. Results: Emodin could inhibit E2-induced MCF-7 cell proliferation and anti-apoptosis effects, and arrest the cell cycle in G0/G1 phase, further blocking the effect of E2 on expression and transcriptional activity of $ER{\alpha}$. Moreover, Emodin influenced the ER ${\alpha}$ genomic pathway via downregulation of cyclin D1 and Bcl-2 protein expression, and influenced the non-genomic pathway via decreased PI3K/Akt protein expression. Conclusions: These findings indicate that emodin exerts inhibitory effects on MCF-7 cell proliferation via inhibiting both non-genomic and genomic pathways.