• Journal of Life Science
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• v.23 no.3
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• pp.355-360
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• 2013

Withaferin A is an active component of Withania somnifera, and has anti-inflammatory, anti-tumor, and immune modulatory effects. However, the effects of withaferin A on metalloproteinase (MMP)-9 expression and activity have not been investigated. In this study, we investigated the ability of withaferin A to inhibit MMP-9 expression and activity in PMA-treated human cervical carcinoma Caski cells. Withaferin A markedly inhibited the PMA-induced MMP-9 activity in a dose-dependent manner. Withaferin A decreased not only PMA-induced MMP-9 promoter activity but also PMA-mediated MMP-9 mRNA and protein expression in Caski cells. NF-${\kappa}B$ promoter activity, which is important in MMP-9 expression, was also decreased in combined treatment with withaferin A and PMA. Furthermore, withaferin A markedly suppressed the ability of PMA-mediated migration in Caski cells. Our findings suggest that withaferin A might inhibit PMA-induced migration through the down-regulation of MMP-9 expression and activity.

• BMB Reports
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• v.53 no.8
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• pp.419-424
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• 2020

Bee venom (BV), secreted from the venom gland of the honey bee, contains several biological active compounds. BV has been widely used as a traditional medicine for treating human disease, including cancer. In this study, we have shown the molecular mechanism underlying the therapeutic effect of BV on cancer. Treatment with BV reduced the proliferation of cervical-cancer cells in a dose- and time-dependent manner. Interestingly, the killing effect of BV was specific to HPV-positive cervical-cancer cell lines, such as Caski and HeLa cells, and not to HPV-negative cervical-cancer cells (C33A). BV reduced the expression of HPV E6 and E7 at RNA and protein levels, leading to an increase in the expression of p53 and Rb in Caski and HeLa cells. Further, BV decreased the levels of cell-cycle proteins, such as cyclin A and B, and increased the levels of cell-cycle inhibitors, such as p21 and p27. BV significantly induced apoptosis and inhibited wound healing and migration of cervical-cancer cells. It also upregulated the expression of pro-apoptotic BAX and downregulated the expression of anti-apoptotic Bcl-2 and Bcl-XL. Cleavage of caspase-3, caspase-9, and PARP were also induced by BV treatment, whereas the phosphorylation of mitogenic signaling-related proteins, such as AKT, JNK, p38, and ERK, were downregulated. Our results indicate that BV has a therapeutic selectivity for HPV-positive malignant cells, so further clinical studies are needed to assess its clinical application.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.10
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• pp.1525-1530
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• 2005

The purpose of this study is to investigate anti-tumor activities, general composition, elemental composition and mineral contents of fermented liquid stem, root and fruit of Opuntia humifusa. In the general composition, the energy, crude protein, crude lipid and crude carbohydrate contents of fermented liquid stem were 86.21 Kcal, 0.92$\%$, 0.12$\%$, and 20.34$\%$, respectively. Fermented liquid fruit showed 65.32 Kcal, 1.04$\%$, 0.08$\%$, and 15.15$\%$. In mineral analysis, fermented liquid stem and fruit showed 1,800 and 388 mg of calcium per 100g. The ferrous concentrations of fermented liquid stem and fruit were 21 and 10 mg per 100 g, respectively. Methanol, ethanol and water extracts of nonfermented liquid stem and fruit did not inhibit the proliferation in human cervical cancer cells (Caski, SiHa and HaCaT), but the fermented liquid fruit showed the inhibition of Proliferation with dose-response manner in Caski and SiHa cells, but not HaCaT. Therefore, it suggests that fermented cactus may be used as one of potential adjuvant for the treatment of cervical carcinomas.

• Journal of Life Science
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• v.16 no.6
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• pp.964-971
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• 2006

The cancer cells, characterized by local invasion and distant metastasis, are very dependant on extracellular matrix. The expression of matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. Among the human MMPs, matirx metalloproteinase-2 (MMP-2) and matrix metalloproteinse-9 (MMP-9) are key enzymes that degrade type IV collagen of the matrix. Here, we studied the effect of disulfiram, an anti-tumor compound, on the suppression of the tumor invasion and the activity of MMP-2, MMP-9 in human osteosarcoma cells (U2OS). Disulfiram had the type IV collagenase inhibitory activity, the effect of inhibition of gene and protein expression, and these inhibitions were responsible for blocking invasion through cell mediated and non-cell mediated pathways. In conclusion, disulfiram inhibited expression of MMP-2 and MMP-9, and regulated the invasion of U2OS, Caki-1 and Caski. These observations raise the possibility of clinical therapeutic applications for disulfiram used as a potential inhibitor of cancer invasion.

• Journal of Dairy Science and Biotechnology
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• v.22 no.2
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• pp.99-106
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• 2004

Tumor cell proliferation inhibitory, antioxidative activities and glutathione content were analyzed in a variety of spore forming lactic acid bacteria. Tumor cell proliferation inhibitory activity varied widely depending upon the strains of spore forming lactic acid bacteria and the types of carcinoma cell lines(0${\simn}$56.7%), Bacillus coagulans KTCC3625 has shown a marked antipro-liferative effect against the carcinoma cells and NCL-H1299 human lymphoma cell line tended to be least affected by the spore forming lactic acid bacterial cell extracts. Antioxidative activity analyzed in the lipid peroxidation occurred in all the test strains varied on the strains(5.0 to 52.0%) an extensively high degree of antioxidative activity was demonstrated by three strains of Bacillus coagulans KTCC3625, Bacillus coagulans KTCC1015 and Lactobacillus sporogens CU 815. Concentrations of glutathione were highest in a strain of Lactobacillus sporogenes CU 815 followed by Sporo-lactobacillus inulinus ATCC13538 (5.34 to 8.19 mol/g). Spearmans' rank correlation quotient between cellular GSH levels and linoleic acid peroxidation inhibitory effects of the spore forming lactic acid bacteria revealed highly significant correlation quotient of 0.78. Spearmans' rank correlation quotient between the Caski human cervix carcinoma cell proliferation inhibitory activity and the linoleic acid peroxidation inhibitory effects of the spore forming lactic acid bacteria and that between Caski carcinoma cell proliferation inhibitory activity and the cellular GSH levels were shown to be 0.29 and 0.32,respectively, which means an insignificant positive correlation however.

• Korean Journal of Food Science and Technology
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• v.32 no.6
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• pp.1389-1395
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• 2000

Cervical cancer has been one of the leading causes of female death from cancer worldwide with about 500,000 deaths per year. A strong association between certain human papillomaviruses (HPV types 16 and 18) and cervical cancer has been well known. An extract of natural products, Rhus, has been used to investigate whether this agent has the ability of inhibiting the oncogenes E6 and E7 of HPV type 16. This Rhus inhibited the proliferation of human cervical cancer cell lines (C-33A, SiHa, Caski) and HaCaT keratinocytes in a dose response manner. In vitro binding assay and ELISA showed that Rhus inhibited the in vitro binding of E6 and E6AP which are essential for the binding and degradation of the tumor suppressor p53. In addition, Rhus inhibited the in vitro binding of E7 and Rb which essential tumor suppressor for the control of cell cycle. The level of mRNA for E6 was also decreased by Rhus while that of E7 mRNA was not changed. Our data suggested that Rhus inhibited the oncogenecity of E6 and E7 of HPV 16 type, thus can be used as a putative anti-HPV agent for the treatment of cervical carcinomas by HPV.

• Journal of Gynecologic Oncology
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• v.29 no.6
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• pp.95.1-95.17
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• 2018

Objective: Cervical cancer is one of the most common malignant tumors. Our previous results showed that long non-coding RNA (lncRNA) XLOC_006390 plays an important role in cervical cancer. In this study, we have explored the mechanism of action of lncRNA XLOC_006390. Methods: LncRNA XLOC_006390 was proposed to exercise its function as a competing endogenous RNA (ceRNA), and its potential targeted miRNAs was predicted through the database LncBase Predicted v.2. Two miRNAs, miR-331-3p, and miR-338-3p, were chosen for the study. Expression of miRNAs and lncRNA in cervical cancer cells and tissues was detected by reverse transcription polymerase chain reaction. To determine the correlation, silencing of XLOC_006390, over-expression of miR-331-3p, and miR-338-3p was performed in SiHa and Caski cell lines, respectively. Results: Based on the interactive effect between miRNA and lncRNA, miR-331-3p and miR-338-3p were significantly downregulated in cervical cancer cells and tissues, and their expression levels were negatively related to that of lncRNA. Our results also showed that the expression of miR-331-3p target gene NRP2, miR-338-3p target genes PKM2, EYA2 was significantly downregulated when the XLOC_006390 was knocked down. Further, XLOC_006390 was found to facilitate cervical cancer tumorigenesis and metastasis by downregulating miR-331-3p and miR-338-3p expression. Conclusion: Taken together, our study demonstrated that XLOC_006390 may serve as a ceRNA and reversely regulates the expression of miR-331-3p and miR-338-3p, thus facilitating cervical cancer tumorigenesis and metastasis.