Cancer metastasis is a major cause of death in cancer patients, with invasion as a first step greatly contributing to the failure of clinical treatments. Any compounds with an inhibitory influence on this process are therefore of prime interest. Momordica charantia (bitter melon) is widely consumed as a vegetable and especially as a folk medicine in Asia. Here, we investigated the anti-invasive effects of bitter melon leaf extract (BMLE) on a rat prostate cancer cell line (PLS10) in vitro and in vivo. The results indicated that nontoxic concentrations of BMLE significantly inhibited the migration and invasion of cells in vitro. The results of zymography showed that BMLE inhibited the secretion of MMP-2, MMP-9 and urokinase plasminogen activator (uPA) from PLS10. Real-time RT-PCR revealed that BMLE not only significantly decreased gene expression of MMP-2 and MMP-9, but also markedly increased the mRNA level of TIMP-2, known to have inhibitory effects on the activity of MMP-2. An EnzChek gelatinase/collagenase assay showed that collagenase type IV activity was partially inhibited by BMLE. In the in vivo study, intravenous inoculation of PLS10 to nude mice resulted in a 100% survival rate in the mice given a BMLE-diet as compared with 80% in the controls. The incidence of lung metastasis did not show any difference, but the percentage lung area occupied by metastatic lesions was slightly decreased in the 0.1% BMLE treatment group and significantly decreased with 1% BMLE treatment as compared with the control. Thus, the results indicate for the first time an anti-metastatic effect of BMLE both in vitro and in vivo. (Cancer Sci 2010; 101: 2234-2240 P rostate cancer is the most common male malignant tumor in Western countries.(1) Androgen ablation therapy is widely used for the initial stage of this disease and may produce favorable outcome, but most patients eventually develop ablationresistant prostate cancers with metastatic foci. Currently, there is no treatment that is able to cure progressive hormone-refractory metastatic prostate cancer.Metastasis is a multi-step process, which involves a series of processes including cellular adhesion and invasion through the basement membrane, transfer via the circulation system, extravasation, and proliferation at a distant site.(2,3) Multiple organ failure caused by multiple metastasis is a major cause of death in cancer patients. Therefore, prevention of tumor metastasis is one primary goal. However, cytotoxic agents have generally been applied for tumor metastasis therapy, with serious sideeffects that can diminish the quality of life of cancer patients. Recently, many efforts have therefore been made to search for non-or low-cytotoxic agents that can reduce the spread of malignant tumors. One focus is on cell invasion using substances in medicinal plants. (5,6) Momordica charantia, or bitter melon, has long been frequently used in various Asian traditional medicine systems and commonly consumed as a vegetable. (7,8) (19) Our previous study showed that the bitter melon ...

The results indicate that PFJ and EA are potential chemopreventive agents for prostate cancer, and EA may be the active component of PFJ that exerts these anti-cancer effects.

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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.

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The objective of this study was to investigate the in vitro bioactivities associated with the content of phytochemicals in the extracts from perilla seed meal extract (PSME) compared with dietary seed (PSE). PSE had higher total phenolics and flavonoids content than PSME. However, hydrophilic phytochemical contents in PSME were quantitatively equivalent to PSE. Rosmarinic acid was predominantly found in both extracts. Cell viability and anti‐mutagenicity testing demonstrated that PSE and PSME were biosecured and non‐genotoxic. Both extracts strongly scavenged free radicals and significantly reduced reactive oxygen species (ROS) production. The extracts drastically diminished nitric oxide (NO) production of LPS‐treated RAW 264.7 cells via iNOS mRNA expression. The expression of IL‐6 and COX‐2 were evidently inhibited by these extracts. It could be concluded that PSE and PSME clearly showed in vitro anti‐mutagenicity, antioxidant and anti‐inflammatory capacities. In particular, the by‐product perilla seed meal could be considered as a high nutritive functional food. Practical applications This study suggests that the seed meals, a by‐product from seed oil industry, can be utilized as a valuable dietary source for humans and animals. The high content of polyphenols and their bioactivities can be developed as functional foods, and excipients and fillers in pharmaceuticals and nutraceuticals production. Moreover, recycling of the by‐product seed meals should also reduce environmental and sanitary pollution.

To reduce cancer mortality, understanding of mechanisms of cancer metastasis is crucial. We have established six rat hepatocellular carcinoma (HCC) cell lines, which exhibit differing metastatic potential to the lung after inoculation into the tail veins of nude mice. In the present experiment, we investigated the process of cell attachment to metastatic sites and possible regulating factors. One hour after inoculation, two of two HCC cell lines with high metastatic potential and one of two HCC cell lines with low metastatic potential exhibited many attached cells in the lung. One day after inoculation, lung metastatic foci were observed only with highly-metastatic cells with elevated connexin 43 (Cx43) expression as assessed by cDNA array analysis. Furthermore, 24 or 48 h after transfection of an siRNA targeting Cx43, in vitro invasion and migration were suppressed by 68% (P < 0.001) and 36% (P < 0.05) compared with control-siRNA transfected cells, despite no differences in cellular morphology, cell proliferation or apoptotic activity. Moreover, the number of metastatic nodules per lung area in nude mice was significantly (P < 0.01) reduced. In conclusion, suppression of Cx43 expression in tumor cells reduced in vitro migration and invasion capacity and in vivo metastatic ability so that Cx43 has potential as a molecular target for prevention of cancer metastasis with Cx43 overexpressing tumors. (Cancer Sci 2012; 103: 860-867) D espite significant improvements in diagnosis, surgical techniques, general patient care and local and systemic adjuvant therapies, most deaths from cancer are due to metastases that are resistant to conventional therapies. To reduce cancer mortality, an understanding of the mechanisms of cancer metastasis and the development of treatments focusing on prevention and/or care of metastases are a high priority.We have established six rat hepatocellular carcinoma (HCC) cell lines(1) from an in vivo rat HCC model, (2)(3)(4) in which combination treatment of N-nitrosomorpholine and diethylnitrosamine induces liver tumors metastasizing to the lung. These cell lines (HSU-C1, -C2, -C5F, -C6, -N1 and -L2) show similar in vitro doubling times but widely differing metastatic ability after inoculation into the tail vein or transplantation into the subcutis of nude mice.(1) In particular, the N1 and L2 lines are particularly metastatic to the lung when inoculated into the tail vein, as compared with the other lines. All these lines express the glutathione S-transferase placental form (GST-P), known to be upregulated during rat hepato-carcinogenesis, from preneoplastic liver cell foci to hepatocellular carcinoma.(5-7) Thus, immunohistochemistry for rat GST-P can readily visualize the cells in mouse tissue.Metastasis is a multi-step process, involving angiogenesis, invasion, detachment, circulation, adhesion and extravasation.(8) The genes and factors responsible for promotion or suppression of metastasis are multiple for each step and reasons for differences in metastatic potential remain to be eluc...

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