Selenium inhibits growth of trastuzumab-resistant human breast cancer cells via downregulation of Akt and beclin-1.

The response rate to treatment with trastuzumab (Tz), a recombinant humanized anti-HER2 monoclonal antibody, is only 12-34% despite demonstrated effectiveness on improving the survival of patients with HER2-positive breast cancers. Selenium has an antitumor effect against cancer cells and can play a cytoprotective role on normal cells. This study investigated the effect of selenium on HER2-positive breast cancer cells and the mechanism in relation to the response of the cells to Tz. HER2-positive breast cancer cell lines, SK-BR-3 as trastuzumab-sensitive cells, and JIMT-1 as Tz-resistant cells were treated with Tz and sodium selenite (selenite). Cell survival rates and expression of Her2, Akt, and autophagy-related proteins, including LC3B and beclin 1, in both cell lines 72 h after treatment were evaluated. Significant cell death was induced at different concentrations of selenite in both cell lines. A combined effect of selenite and Tz at 72 h was similar to or significantly greater than each drug alone. The expression of phosphorylated Akt (p-Akt) was decreased in JIMT-1 after combination treatment compared to that after only Tz treatment, while p-Akt expression was increased in SK-BR-3. The expression of beclin1 increased particularly in JIMT-1 after only Tz treatment and was downregulated by combination treatment. These results showed that combination of Tz and selenite had an antitumor effect in Tz-resistant breast cancer cells through downregulation of phosphorylated Akt and beclin1-related autophagy. Selenite might be a potent drug to treat Tz-resistant breast cancer by several mechanisms.

3-bromopyruvate and buthionine sulfoximine effectively kill anoikis-resistant hepatocellular carcinoma cells.

BACKGROUND & AIMS: Acquisition of anoikis resistance is a prerequisite for metastasis in hepatocellular carcinoma (HCC). However, little is known about how energy metabolism and antioxidant systems are altered in anoikis-resistant (AR) HCC cells. We evaluated anti-tumor effects of a combination treatment of 3-bromopyruvate (3-BP) and buthionine sulfoximine (BSO) in AR HCC cells. METHODS: We compared glycolysis, reactive oxygen species (ROS) production, and chemoresistance among Huh-BAT, HepG2 HCC cells, and the corresponding AR cells. Expression of hexokinase II, gamma-glutamylcysteine synthetase (rGCS), and epithelial-mesenchymal transition (EMT) markers in AR cells was assessed. Anti-tumor effects of a combination treatment of 3-BP and BSO were evaluated in AR cells and an HCC xenograft mouse model. RESULTS: AR HCC cells showed significantly higher chemoresistance, glycolysis and lower ROS production than attached cells. Expression of hexokinase II, rGCS, and EMT markers was higher in AR HCC cells than attached cells. A combination treatment of 3-BP/BSO effectively suppressed proliferation of AR HCC cells through apoptosis by blocking glycolysis and enhancing ROS levels. In xenograft mouse models, tumor growth derived from AR HCC cells was significantly suppressed in the group treated with 3-BP/BSO compared to the group treated with 3-BP or sorafenib. CONCLUSIONS: These results demonstrated that a combination treatment of 3-BP/BSO had a synergistic anti-tumor effect in an AR HCC model. This strategy may be an effective adjuvant therapy for patients with sorafenib-resistant HCC.

Berberine-induced growth inhibition of epithelial ovarian carcinoma cell lines.

AIM: The aim of this study is to analyze the impact of berberine on the two human epithelial ovarian carcinoma cell lines OVCAR-3 and SKOV-3 in relation to the potential usefulness of berberine in the treatment of epithelial ovarian cancer. METHODS: Under adherent culture conditions, the cell lines were treated with berberine and analyzed for changes in cell growth. The cell cycle duration and degree of apoptosis were evaluated by means of propidium iodide staining and Annexin V staining. RESULTS: After the berberine treatment, the two cell lines showed a dose-dependent reduction in the growth rate. In the cell cycle analysis, the OVCAR-3 and SKOV-3 cells showed an increased DNA content of 5% in the G2/M phase and 7% in the S phase, respectively. Additionally, the results confirm the cell cycle arrest by immunoblotting and the up-regulation of p27; however, in the apoptosis analysis, neither cell line showed an increase in apoptosis after the berberine treatment. CONCLUSION: Berberine treatment can inhibit proliferation through a cell cycle arrest in OVCAR-3 and SKOV-3 cells. Thus, berberine may be a novel anticancer drug for the treatment of ovarian cancer.

Sulforaphane inhibits oral carcinoma cell migration and invasion in vitro.

Sulforaphane is a predominant isothiocyanate in Brassica oleracea, a family of cruciferous vegetables, and is known to be inversely related to the risk of various types of human carcinomas. Studies using oral carcinoma cell lines are scarce, however, and the role of sulforaphane on oral carcinoma cell metastasis is yet to be determined. In this study, the growth inhibition of oral carcinoma cell lines by sulforaphane was determined using aqueous soluble tetrazolium salts, and the growth of various oral cancer cell lines was attenuated. The migration and invasion activities of the cells also decreased, as observed in monolayer scratch assays and transwell invasion experiments. The molecular change behind the impairment of the migration and invasion was investigated via secreted metalloprotease level detection using Multiplex protein analysis kits. At the molecular level, the secreted forms of MMP-1 and MMP-2 were down-regulated. The expressions of MMP-1 and MMP-2 did not change when a conventional tumoricidal agent paclitaxel was used. These findings indicate that sulforaphane may have therapeutic potential as an inhibitor of metastasis in oral carcinoma patients.

Ischemic colitis after mesotherapy combined with anti-obesity medications.

Mesotherapy and anti-obesity medications are gradually gaining worldwide popularity for purposes of body contouring and weight loss. Their adverse effects are various, but there is a tendency to disregard them. Ischemic colitis is one of the most common diseases associated with non-obstructive blood vessel disorders. However, there have been no case reports about the adverse effects resulting from mesotherapy only or in combination with anti-obesity medications. We report on an interesting case of ischemic colitis after mesotherapy combined with anti-obesity medications in a 39-year-old female who had no risk factors.

Berberine diminishes the side population and ABCG2 transporter expression in MCF-7 breast cancer cells.

The plant alkaloid berberine has many biological activities including the ability to induce cell cycle arrest and apoptosis, making it a potentially useful agent for targeting cancer cells. We have analyzed the effects of berberine on MCF-7 breast cancer cells. Berberine was added to MCF-7 cells in culture, and proliferation, side population (SP) cells and expression of ABCG2 were examined. Berberine caused a dose-dependent reduction in proliferation. Hoechst 33,342 dye staining and FACS analysis revealed that berberine treatment caused a decrease in SP cells relative to untreated controls. In addition, berberine treatment was associated with a decrease in expression of ABCG2 relative to untreated controls. These results indicate that the growth inhibitory effects of berberine treatment on MCF-7 cells may be partly via effects on SP and ABCG2 expression. Further work is warranted to explore whether berberine may be a novel therapeutic drug useful for targeting breast cancer stem cells.

Berberine inhibits growth of the breast cancer cell lines MCF-7 and MDA-MB-231.

The effects of berberine on the behavior of breast tumors have not yet been established. To determine whether this compound is useful in the treatment of breast cancer, we analyzed the impact of berberine on the human breast cancer cell lines MCF-7 and MDA-MB-231 cells. Berberine was added to proliferating MCF-7 and MDA-MB-231 cells in culture. Following treatment, changes in cell growth characteristics such as proliferation, cell cycle duration, and the degree of apoptosis were assayed. Following berberine treatment, a time-dependent reduction in proliferation was observed in both cell lines at differing concentrations: 20 microM for MCF-7 and 10 microM for MDA-MB-231 cells. Annexin V staining showed an increase in apoptosis in both cell lines of 31 % in MCF-7 and 12 % in MDA-MB-231 cells compared to their respective controls. In addition, 12 % of the MCF-7 cells were arrested at G0/G1, compared to 62 % of control cells. These results demonstrate that treatment with berberine inhibits growth in both MDA-MB-231 and MCF-7 cells. In addition, they show that this partly occurs through the induction of apoptosis in MDA-MB-231 cells, and through both cell cycle arrest and induction of apoptosis in MCF-7 cells. Thus, berberine may be a novel therapeutic drug for breast cancer.