Fucoidan, a major component of brown seaweed, prohibits the growth of human cancer cell lines in vitro.

Fucoidan, the general term for sulfated polysaccharides, is reported to engage in various biological activities having anti-tumor, anti-coagulation and anti-viral effects. Though it has been investigated, the mechanism of its anti-tumor effects remains elusive. The current study examined the anti-tumor effects of fucoidan extracted from Okinawa mozuku on 15 human cancer cell lines (6 hepatocellular carcinomas, 1 cholangiocarcinoma, 1 gallbladder cancer, 2 ovarian cancers, 1 hepatoblastoma, 1 neuroblastoma and 3 renal cancers) using an MTT assay. Changes in apoptosis and the cell cycle were analyzed by flow cytometry. The results revealed that cell proliferation was suppressed in 13 cell lines in a time- and/or dose-dependent manner; this suppression was marked in the hepatocellular carcinoma, cholangiocarcinoma and gallbladder carcinoma cell lines. In contrast, proliferation of the neuroblastoma and 1 of the 2 ovarian carcinoma cell lines was not affected. The ratio of apoptotic cells significantly increased in 5 of the 6 hepatocellular carcinoma cell lines, and the ratio of G2/M cells increased in the 3 hepatocellular cell lines examined. These observations indicate that fucoidan is a potential anti-tumor agent for the treatment of bile duct cancers, such as hepatocellular carcinoma, cholangiocarcinoma and gall-bladder carcinoma.

Growth inhibitory effects of IFN-beta on human liver cancer cells in vitro and in vivo.

We investigated the effects of interferon-beta (IFN-beta) on the growth of human liver cancer cells. The effects of IFN-beta with or without 5-fluorouracil (5-FU) on the proliferation of 13 liver cancer cell lines were investigated in vitro. Chronologic change in IFN-alpha receptor 2 (IFNAR-2) expression was monitored in hepatocellular carcinoma (HCC) cells (HAK-1B) cultured with IFN-beta. After HAK-1B cells were transplanted into nude mice, various doses of IFN-beta were administered, and the tumor volume, weight, histology, tumor blood vessel, and angiogenesis factor expression were examined. IFN-beta inhibited the growth of 11 cell lines with apoptosis in a dose-dependent and time-dependent manner. With IFN-beta, IFNAR-2 expression in HAK-1B cells was significantly downregulated from 6 to 12 h. IFN-beta induced a dose-dependent decrease in tumor volume and weight and a significant increase of apoptosis in the tumor. Both basic fibroblast growth factor (bFGF) and blood vessel number in the tumor decreased only in mice receiving the lowest dose (1000 IU) of IFN-beta. IFN-beta with 10 muM of 5-FU frequently induced synergistic antiproliferative effects. IFN-beta with or without 5-FU induces strong antitumor effects in HCC cells, and we conclude that IFN-beta is useful for the prevention and treatment of HCC.

Effects of IFN-alpha on alpha-fetoprotein expressions in hepatocellular carcinoma cells.

We investigated the effects of pegylated (PEG)-IFN-alpha2b on alpha-fetoprotein (AFP) expression as demonstrated by protein and mRNA levels in six human hepatocellular carcinoma (HCC) cell lines. The number of KIM-1 cells in culture with PEG-IFN-alpha2b decreased between 24 amd 240 h, whereas the levels of intracellular and secreted AFP per cellular protein increased (except at 192 h), with levels 1.9-fold and 2.9-fold higher at maximum, respectively, than cells without PEG-IFN-alpha2b (control). The mRNA level increased between 72 and 192 h, when the level was 3-fold higher than that of the control. In the 72-h culture with 40-5000 IU/mL PEG-IFN-alpha2b, there were dose-dependent increases in AFP protein and mRNA expression and dose-dependent decrease in cell number resulting from apoptosis and blockage of the cell cycle at the S-phase. The rate of fucosylated AFP in the cell lysate decreased in a dose-dependent and time-dependent manner. In the PEG-IFN-alpha2b culture of the other five HCC cell lines, cell proliferation was suppressed, but the expressions of AFP protein and mRNA increased in only two cell lines, and suppression of cell proliferation was not related to the increase in AFP expressions. Our findings demonstrated that PEG-IFN-alpha2b induces an increase in AFP expression at both the protein and mRNA levels.

Growth inhibitory effects of pegylated IFN alpha-2b on human liver cancer cells in vitro and in vivo.

PURPOSE: We investigated the effects of pegylated IFN-alpha2b (PEG-IFN-alpha2b) on the growth of human liver cancer cells. METHODS: The effect of PEG-IFN-alpha2b on the proliferation of 13 liver cancer cell lines was investigated in vitro. Chronological changes in growth and IFN-alpha receptor-2 (IFNAR-2) expression were monitored in hepatocellular carcinoma (HCC) cells (HAK-1B) cultured with PEG-IFN-alpha2b. After HAK-1B cells were transplanted into nude mice, various doses of PEG-IFN-alpha2b or IFN-alpha2b were administered, and tumor volume, weight, histology, and IFNAR-2 expression were examined. RESULTS: PEG-IFN-alpha2b inhibited the growth of nine cell lines with apoptosis in a dose- and time-dependent manner. Continuous contact with PEG-IFN-alpha2b induced time-dependent growth inhibition and down-regulation of IFNAR-2 expression. PEG-IFN-alpha2b induced a dose-dependent decrease in tumor volume and weight, a significant increase of apoptotic cells, and a decrease in IFNAR-2 expression in the tumor. The clinical dose for chronic hepatitis C was also effective. The antitumor effect of PEG-IFN-alpha2b was significantly stronger than that of non-PEG-IFN-alpha2b in vivo. CONCLUSIONS: Continuous contact with PEG-IFN-alpha2b induces strong antitumor effects and the down-regulation of IFNAR-2 in HCC cells. The data suggest potential clinical application of PEG-IFN-alpha2b for the prevention and treatment of HCC.

Immunohistochemical expression of Mina53 and Ki67 proteins in human primary gingival squamous cell carcinoma.

Studies have reported the presence of relationships between the Myc target gene Mina53 and poor prognostic factors in several cancers including esophageal cancer. In this study, we investigated the relationships between Mina53 expression in gingival squamous cell carcinoma and clinicopathological factors. Seven samples of normal and dysplastic gingival tissues and 15 samples of gingival squamous cell carcinoma were immunostained for Mina53 and Ki67, and examined for the relationships between their expression and differentiation degree, lymph node metastasis, stage, tumor diameter, and prognosis. In normal and dysplastic gingival tissues, the localization of the expression of Mina53 and Ki67 was similar, but that in gingival squamous cell carcinoma tissue varied depending on the degree of differentiation. In well-differentiated GSCC with pearl formation, Mina53 was negative at the center of the clearly keratinized cancer nest, but positive in the nuclei of cells in the periphery and adjacent area of the cancer nest. In diffusely proliferating undifferentiated and moderately-differentiated GSCC showing no pearl formation, both Mina53 tended to be positive in the nuclei of cancer cells in the entire cancer nest. A significant correlation was found between the expression of Mina53 and that of Ki67 in patients with gingival squamous cell carcinoma or dysplastic gingiva. No significant correlation was noted between the expression of Mina53 or Ki67 and prognostic factors such as the degree of differentiation, lymph node metastasis, stage, and tumor diameter. In gingival squamous cell carcinoma, Mina53 expression was correlated with the proliferation of tumor cells, but unlike esophageal and other squamous cell carcinomas, not with the prognosis. The absence of correlations with prognostic factors suggests that may differ gingival squamous cell carcinoma differs biologically from esophageal squamous cell carcinoma which is correlated with Mina53 in terms of the biological expression of Mina53.