beta-escin and Adenocarcinoma

Four types of aescin that are available on the pharmaceutical market, beta-aescin crystalline, beta-aescin amorphous, beta-aescin sodium and aescin polysulfate, have been analyzed for their cytotoxic effects on human colon adenocarcinoma (LoVo) and doxorubicin-resistant human colon adenocarcinoma cell lines (LoVo/Dx). Their cytotoxic activities were evaluated by sulforhodamine B (SRB) and methyl tetrazolium (MTT) assays. All four types of aescin exerted strong dose-dependent cytotoxicity to LoVo and, to a lesser degree, LoVo/Dx cell lines. The IC50 value for the LoVo/Dx cell line was higher, but still dose-dependent. Results from both assays demonstrated that p-aescin crystalline has the most cytotoxic activity toward human colon adenocarcinoma cell lines.

Topics: Adenocarcinoma; Aesculus; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Doxorubicin; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Escin; Humans

Escin, a natural mixture of triterpene saponins isolated from horse chestnut, has been reported to possess anticancer activity in many human cancer cells. However, the effect of escin on the metastasis has not been studied. The present study examined the effect of escin on the migration and invasion of AGS human gastric cancer cells. To examine the effects of escin on metastatic capacities of gastric cancer cells, AGS cells were cultured in the presence of 0-4 μmol/L escin. Escin inhibited cell migration and invasion in AGS cells. However, escin did not affect the viability of these cells at these concentrations. The chemokine receptor and its ligands play an important role in cancer metastasis. Escin decreased the production of soluble C-X-C motif chemokine (CXCL)16 but increased the expression of trans-membranous CXCL16. The expression of C-X-C chemokine receptor (CXCR)6 was not affected by escin treatment. Exogenous CXCL16 reversed escin-induced migration inhibition. In addition, escin inhibited the phosphorylation of focal adhesion kinase and Akt. These results demonstrate that escin inhibited the migration and invasion of AGS cells, which is associated with altered CXCL16/CXCR6 axis. These findings suggest that escin has potential as an antimetastatic agent in gastric cancer.

Topics: Adenocarcinoma; Cell Line, Tumor; Cell Movement; Cell Survival; Chemokine CXCL16; Chemokines, CXC; Escin; Focal Adhesion Kinase 1; Humans; Neoplasm Invasiveness; Phosphorylation; Proto-Oncogene Proteins c-akt; Receptors, Chemokine; Receptors, CXCR6; Receptors, Scavenger; Receptors, Virus; Signal Transduction; Stomach Neoplasms

Lung cancer is the leading cause of cancer-related deaths. β-Escin, a triterpene saponin isolated from horse chestnut seeds, was tested for inhibition of lung adenoma and adenocarcinoma induced by the tobacco carcinogen 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in female A/J mice; and its possible mode of action was evaluated using the H460 human lung cancer cell line. At 6 weeks of age, 35 mice were fed AIN-76A-modified diet, and one week later, lung tumors were induced with a single intraperitoneal (i.p.) injection of 10 μmol NNK/mouse. Three weeks after the NNK treatment, groups of mice were fed either control or experimental diets containing 500 ppm for 20 weeks (10 control, 5 β-escin) or 36 weeks (15 control, 5 β-escin) and evaluated for lung tumor via histopathologic methods. Administration of 500 ppm β-escin significantly suppressed lung tumor (adenoma + adenocarcinoma) formation by more than 40% (P < 0.0015) at 20 weeks and by 53.3% (P < 0.0001) at 37 weeks. β-Escin inhibited NNK-induced lung adenocarcinoma formation by 65% (P < 0.001) at 20 weeks and by 53% (P < 0.0001) at 37 weeks. Immunohistochemical analysis revealed that lung tumors from mice exposed to β-escin showed significantly reduced aldehyde dehydrogenase (ALDH)1A1 and phospho-Akt (p-Akt) expression when compared with those in mice fed control diet. Aldefluor assay for ALDH revealed that among H460 lung cancer cells treated with different concentrations of β-escin (0-40 μmol/L), the subpopulation of cells with elevated ALDH activity was inhibited significantly. Our findings suggest that β-escin inhibits tobacco carcinogen-induced lung tumor formation by modulating ALDH1A1-positive cells and RhoA/Rock signaling.

Topics: Adenocarcinoma; Adenoma; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase 1 Family; Animals; Carcinogenesis; Cell Line, Tumor; Disease Progression; Escin; Female; Flow Cytometry; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Mice; Neoplasm Transplantation; Nicotiana; Nitrosamines; Plant Extracts; Real-Time Polymerase Chain Reaction; Retinal Dehydrogenase; rho GTP-Binding Proteins; rho-Associated Kinases; rhoA GTP-Binding Protein