• Journal of Gastric Cancer
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• v.20 no.3
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• pp.300-312
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• 2020

Purpose: Circular RNAs (circRNAs) are a new class of RNA molecules whose function is largely unknown. There is a growing evidence that circRNAs play an important regulatory role in the progression of a variety of human cancers. However, the exact roles and the mechanisms of circRNAs in gastric cancer are not clear. In this study, we aimed to elucidate the mechanism of hsa_circ_0005556. Materials and Methods: Real-time quantitative polymerase chain reaction was used to detect the expression of hsa_circ_0005556, miR-4270, and matrix metalloproteinase-19 (MMP19) in gastric cancer tissues and cell lines. The expression of hsa_circ_0005556 in gastric cancer cells was silenced by lentivirus, and cell proliferation, invasion, migration, and tumorigenesis in nude mice were assessed to evaluate the function of hsa_circ_0005556 in gastric cancer. Results: The expression of hsa_circ_0005556 in gastric cancer tissues and gastric cancer cell lines was higher compared to normal controls. In vitro, the downregulation of hsa_ circ_0005556 significantly inhibited proliferation, migration, and invasion of gastric cancer cells. In vivo, the downregulation of hsa_circ_0005556 suppressed tumor growth in nude mice. Conclusions: Our study shows that the hsa_circ_0005556/miR-4270/MMP19 axis is involved in proliferation, migration, and invasion of gastric cancer cells through the competing endogenous RNA (ceRNA) mechanism.

• Korean Journal of Pharmacognosy
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• v.49 no.4
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• pp.285-290
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• 2018

Harmine, a beta-carboline alkaloid isolated from the seeds of Peganum harmala has been reported as a promising drug candidate for cancer therapy. However, the effect of harmine on breast cancer remains still unclear. In this study, the effect of harmine on the cell proliferation, migration, and invasion of breast cancer MDA-MB231 cells and the underlying mechanism were investigated. The results indicated that harmine inhibited the proliferation MDA-MB231 cells in a dose-dependent manner and markedly suppressed migration and invasion of MDA-MB231 cells. The mechanism involved in part through Notch signaling. The Notch activity was significantly inhibited by harmine treatment and harmine suppressed the expression of Jagged1 which is a key ligand to activate Notch signaling. These findings suggest a novel mechanism of harmine on anti-cancer activity and harmine may act as a potential therapeutic drug for breast cancer treatment.

• Biomolecules & Therapeutics
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• v.20 no.6
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• pp.556-561
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• 2012

Steroid sulfatase (STS) is responsible for the conversion of estrone sulfate to estrone that can stimulate growth in endocrine-dependent tumors such as prostate cancer. Although STS is considered as a therapeutic target for the estrogen-dependent diseases, cellular function of STS are still not clear. Previously, we found that tumor necrosis factor (TNF)-${\alpha}$ significantly enhances steroid sulfatase expression in PC-3 human prostate cancer cells through PI3K/Akt-dependent pathways. Here, we studied whether bacterial lipopolysaccharides (LPS) which are known to induce TNF-${\alpha}$ may increase STS expression. Treatment with LPS in PC-3 cells induced STS mRNA and protein in concentration- and time-dependent manners. Using luciferase reporter assay, we found that LPS enhanced STS promoter activity. Moreover, STS expression induced by LPS increased PC-3 tumor cell migration determined by wound healing assay. We investigated that LPS induced IL-6 expression and IL-6 increased STS expression. Taken together, these data strongly suggest that LPS induces STS expression through IL-6 pathway in human prostate cancer cells.

• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.411-418
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• 2011

Ginsenoside Rp1 (G-Rp1) is a novel ginseng saponin derivative with anti-tumor activity. However, the biochemical and molecular mechanisms of G-Rp1 on anti-tumor activity are not fully understood. In the present study, we report that G-Rp1 inhibits lung cancer cell proliferation, migration and adhesion in p53 wild-type A549 and p53-defi cient H1299 cells. Anti-proliferative activity of G-Rp1 in lung cancer cells is mediated by enhanced nuclear localization of cyclin-dependent kinase inhibitors including $p27^{Kip1}$ and $p21^{WAF1/Cip1}$, and subsequent inhibition of pRb phosphorylation. We also show that these anti-tumor activities of G-Rp1 in both A549 and H1299 cells appear to be mediated by suppression of mitogenic signaling pathways such as ERK, Akt and $p70^{S6K}$. Taken together, these findings suggest further development and evaluation of G-Rp1 for the treatment of lung cancers with mutated p53 as well as wild-type p53.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6501-6506
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• 2015

There are numerous clinical cases indicating that long-term use of bevacizumab may increase the invasiveness of tumors. However, to date, little is known about underlying molecular mechanisms. Therefore, the purpose of our study was to investigate effects of bevacizumab in four cancer cells lines (WSU-HN6, CAL27, Tca83, and HeLa). It was found to promote migration and invasion in the WSU-HN6 and Tca83 cases, while exerting inhibitory effects in CAL27 and HeLa cells. The signal transducer and activator of transcription (STAT) 3 inhibitors niclosamide and S3I-201 inhibited the STAT3 signal pathway, which is activated by bevacizumab. These inhibitors also substantially blocked bevacizumab-induced migration of WSU-HN6 and Tca83 cells. Bevacizumab upregulated interleukin (IL)-6 and phosphorylated (p)-STAT3 expression time-dependently. Therefore, we propose that bevacizumab has differential effects on the migration of different cancer cell lines and promotes migration via the IL-6/STAT3 signaling pathway.

• The Korean Journal of Food And Nutrition
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• v.30 no.4
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• pp.728-734
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• 2017

After being subjected to different cooking methods, small black beans (Rhynchosia nulubilis) were investigated in order to assess the effects of the retained bioactive compounds. Using uncooked, pan broiled, boiled, steamed, and pressure cooked beans, the inhibitory effects of MCF-7 cell migration were evaluated at protein concentrations of 40, 160, and $640{\mu}m/mL$, using the Boyden's chamber assay. All protein concentrations (40, 160, and $640{\mu}m/mL$) of pan broiled beans showed significant reduction (59.83, 32.48, and 21.37%, respectively) in the rate of cell migration to the lower chambers (p-value less than 0.001). Estimated cell migration rates correlated to the exponential decay between experimentally measured cell migration rates and converted samples. The range of estimated cell migration rate for each 100 mg/mL of cooked sample was as follows: pan broiled (21.16%), boiled (22.48%), steamed (22.48%), pressure cooked (29.52%), and uncooked (35.03%) beans. Our study indicated that selective modifications of cooking methods for small black beans, such as pan broiling, ameliorated the inhibitory effects of MCF-7 cell migration. This suggests that optimized cooking methods increase the nutritional contents of the cooked food.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.4019-4023
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• 2014

Metformin has been shown to be useful in reducing insulin resistance by restoring sensitivity. Recent evidence suggests that metformin might also possess anti-tumour activity. This study aimed to investigate the effects of cisplatin combined with metformin on the proliferation, invasion and migration of HNE1/DDP human nasopharyngeal carcinoma (NPC) cells, and to provide a new target for treating metastasis. The MTT assay was used to assess viability of HNE1/DDP cells after exposure to different concentrations of 2, 5-diaminopyrimidine-4, 6-diol (DDP; 2, 4, 8, 16, and $32{\mu}mol{\cdot}L^{-1}$), metformin (5, 10, 15, 20, and $25{\mu}mol{\cdot}L^{-1}$), and $4{\mu}mol{\cdot}L^{-1}$ of DDP combined with metformin. Wound healing and transwell migration assays were performed to assess cell migration and invasion, and expression of E-cadherin and MMP-9 was detected using Western blotting. MTT assay results showed that DDP could inhibit the proliferation of HNE1/DDP cells in a time- and concentration-dependent manner, with an IC50 of $32.0{\mu}mol{\cdot}L^{-1}$ at 24 h (P < 0.05), whereas low concentrations of DDP had almost no inhibitory effects on cell invasion and migration. DDP combined with metformin significantly inhibited cell invasion and migration. In addition, genes related to migration and invasion, such as those of E-cadherin and MMP-9, showed differential expression in the NPC cell line HNE1/DDP. In the present study, with an increasing concentration of metformin, the expression of MMP-9 was downregulated whereas that of E-cadherin was significantly upregulated. Taken together, our results show that cisplatin combined with metformin has effects on proliferation, invasion, and migration of human NPC cells.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.455-461
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• 2016

Galectins are ${\beta}$-galactoside binding lectins that contain one or more carbohydrate recognition domains. As a consequence of sugar-binding properties, galectins exhibit a variety of interactions with glycoproteins, thus playing important roles in various pathological processes. A number of studies have shown roles of galectins in cancer. Galectin-7 is a prototype member of the galectin family implicated in epithelial stratification and cell migration. It can act as a potent dual regulator in different types of cancer. Galectin-7 may contribute either to neoplastic transformation and tumour progression through regulation of cell growth, cell cycle, angiogenesis, apoptosis and cell migration or may have a protective effect in cancer depending on the tissue type. A perusal of the literature indicates particular roles of galectin-7 in carcinomas and melanomas, while contributions await greater exploration in other types of cancers including sarcomas and leukemia. This review collectively summarizes available literature on expression and roles of galectin-7 in different cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2859-2863
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• 2013

Polyphenolic compounds from pomegranate fruit extracts (PFEs) have been reported to possess antiproliferative, pro-apoptotic, anti-inflammatory and anti-invasion effects in prostate and other cancers. However, the mechanisms responsible for the inhibition of cancer invasion remain to be clarified. In the present study, we investigated anti-invasive effects of ellagic acid (EA) in androgen-independent human (PC-3) and rat (PLS10) prostate cancer cell lines in vitro. The results indicated that non-toxic concentrations of EA significantly inhibited the motility and invasion of cells examined in migration and invasion assays. The EA treatment slightly decreased secretion of matrix metalloproteinase (MMP)-2 but not MMP-9 from both cell lines. We further found that EA significantly reduced proteolytic activity of collagenase/gelatinase secreted from the PLS-10 cell line. Collagenase IV activity was also concentration-dependently inhibited by EA. These results demonstrated that EA has an ability to inhibit invasive potential of prostate cancer cells through action on protease activity.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3519-3528
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• 2012

Inhibitory effects of Maclura amboinenesis Bl, one plant used traditionally for the treatment of cancers, on metastatic potential of highly metastatic B16F10 melanoma cells were investigated in vitro. Cell proliferation was assessed using the MTT colorimetric assay. Details of metastatic capabilities including invasion, migration and adhesion of B16F10 melanoma cells were examined by Boyden Chamber invasion and migration, scratch motility and cell attachment assays, respectively. The results demonstrated that n-hexane and chloroform extracts exhibited potent anti-proliferative effects (p<0.01), whereas the methanol and aqueous extracts had less pronounced effects after 24 h exposure. Bioactivity-guided chromatographic fractionation of both active n-hexane and chloroform extracts led to the isolation of two main prenylated xanthones and characterization as macluraxanthone and gerontoxanthone-I, respectively, their structures being identified by comparison with the spectral data. Interestingly, both exhibited potent effective effects. At non-toxic effective doses, n-hexane and chloroform extracts (10 and $30{\mu}g/ml$) as well as macluraxanthone and gerontoxanthone-I (3 and $10{\mu}M$) significantly inhibited B16F10 cell invasion, to a greater extent than $10{\mu}m$ doxorubicin, while reducing migration of cancer cells without cellular cytotoxicity. Moreover, exposure of B16F10 melanoma cells to high concentrations of chloroform ($30{\mu}g/ml$) and geratoxanthone-I ($20{\mu}M$) for 24 h resulted in delayed adhesion and retarded colonization. As insights into mechanisms of action, typical morphological changes of apoptotic cells e.g. membrane blebbing, chromatin condensation, nuclear fragmentation, apoptotic bodies and loss of adhesion as well as cell cycle arrest in the G1 phase with increase of sub-G1 cell proportions, detected by Hoechst 33342 staining and flow cytometry were observed, suggesting DNA damage and subsequent apoptotic cell death. Taken together, our findings indicate for the first time that active n-hexane and chloroform extracts as well as macluraxanthone and gerontoxanthone-I isolated from Maclura amboinensis Bl. roots affect multistep of cancer metastasis processes including proliferation, adhesion, invasion and migration, possibly through induction of apoptosis of highly metastatic B16F10 melanoma cells. Based on these data, M. amboinensis Bl. represents a potential candidate novel chemopreventive and/or chemotherapeutic agent. Additionally, they also support its ethno-medicinal usage for cancer prevention and/or chemotherapy.