Blockade Of Muc1 Expression By Glycerol Guaiacolate Inhibits Proliferation Of Human Breast Cancer Cells

We sought to determine whether administration of glycerol guaiacolate at an optimal biological dose inhibits human breast cancer cell growth. Human breast cancer MCF-7 and ZR-75-1 cells were treated with glycerol guaiacolate and the therapeutic efficacy and biological activity of this drug was investigated on breast cancer cell growth. MCF-7 cells were injected into the mammary fat pad of overectamized female athymic nude mice. Ten days later, animals were treated with daily intraperitoneal injections of glycerol guaiacolate for six weeks. Tumor size and volume was monitored and immunohistochemical analysis on MUC1, p21 and ki-67 was performed. Glycerol guaiacolate decreased breast cancer cell growth in a dose-dependent manner, decreased cell migration, and caused G1 cell cycle arrest. Our results demonstrate that glycerol guaiacolate inhibits MUC1 protein and mRNA expression levels and significantly increased p21 expression in human breast cancer cells as well as induced PARP cleavage. Similarly, glycerol guaiacolate inhibited breast tumor growth in vivo as well as enhanced p21 expression and decreased breast tumor cell proliferation (ki-67 expression). Collectively, our results demonstrate that glycerol guaiacolate decreased MUC1 expression and enhanced cell growth inhibition by inducing p21 expression in breast cancer cells. These findings suggest that glycerol guaiacolate may provide a novel and effective approach for the treatment of human breast cancer. © 2010 Bentham Science Publishers Ltd

Tolfenamic Acid Decreases C-Met Expression Through Sp Proteins Degradation And Inhibits Lung Cancer Cells Growth And Tumor Formation In Orthotopic Mice

Summary: The nonsteroidal anti-inflammatory drug (NSAID), tolfenamic acid (TA) is emerging as a new anti-cancer agent. TA induces the degradation of specific Specificity protein (Sp) transcription factors, Sp1, Sp3 and Sp4 which are associated with tumor growth and metastasis. In this study we have evaluated the effect of TA on lung cancer using both in vitro and in vivo models. TA in a dose dependent manner inhibited proliferation and cell viability of two different lung cancer cells, A549 and CRL5803. TA treatment for 48 h significantly decreased the expression of Sp1, Sp3 and Sp4. The hepatocyte growth factor receptor, c-Met is overexpressed in a variety of cancers including lung cancer and Sp proteins mediate the regulation of c-Met. TA diminished the expression of c-Met protein and modulates its downstream signaling pathway. Furthermore, TA treatment significantly increased the number of apoptotic cells and pro-apoptotic markers c-PARP and Bax confirming the activation of apoptotic pathways. In vivo studies using the orthotopic mice model for lung cancer showed that TA (25 mg/kg/2 days and 50 mg/kg/2 days) resulted in a dose dependent decrease in tumor formation. The immunohistochemical staining of lung tissue showed high expression of Sp1, Sp3, Sp4, c-Met and phospho Met in control group and a dose dependent decrease in TA treated groups. The crucial findings of this study support that targeting c-Met with a potent inhibitor of Sp proteins is a robust strategy for the implications in lung cancer treatment and TA can serve as a therapeutic agent for this devastating disease. © 2009 Springer Science+Business Media, LLC

Harnessing Nanoparticles To Improve Toxicity After Head And Neck Radiation

This article reports the evaluation of cerium oxide (CeO2) nanoparticles\u27 ability to decrease xerostomia and radiation-induced dermatitis in mice after head and neck radiation. Mice were irradiated using an IC160 x-ray system. Two cohorts were included: (A) No-radiation and (B) 30 Gy/6 fractions, and were randomized into three groups: (1) saline, (2) 15 nM CeO2 and (3) 15 μM CeO2. Stimulated salivary flow and radiation-induced dermatitis were evaluated post radiation. Stimulated sialometry demonstrated improved salivary production in all CeO2 groups in comparison with controls (flow: 204 vs. 115 μL/10 minutes, P = 0.0002). One week post radiation, G-III dermatitis decreased in the 15 μM group in comparison with controls (10% versus 100% incidence, respectively). There was decreased skin hyperpigmentation at 12 weeks in the 15-μM group in comparison with 15-nM and non-CeO2 groups (50%, 70%, and 90% G-II, respectively). This study suggests that CeO2 may be radioprotective for salivary production and reduces G-III dermatitis and skin hyperpigmentation incidence. CeO2 as radioprotectant may be a feasible concept during radiotherapy. From the Clinical Editor: This study demonstrates in a mouse model that cerium oxide (CeO2) nanoparticles may provide an important mechanism in preventing radiation induced xerostomia, a common complication of head and neck radiation treatments. © 2012 Elsevier Inc

Bioluminescence imaging correlates with tumor progression in an orthotopic mouse model of lung cancer

Background and Objectives: To determine whether bioluminescence imaging of human lung cancer cells growing in an orthotopic murine model provides a sensitive tool for monitoring tumor progression in athymic nude mice. Methods: Human lung cancer (A549) cells were stably transfected with the firefly luciferase gene and inoculated into the right lung of athymic nude mice. Seven days after inoculation tumor growth was evaluated using the Kodak in-vivo Imaging System FX and continued to be monitored on a weekly basis. Results: In duplicate experiments, human lung cancer tumors formed in 90% of animal\u27s injected orthotopically. The mean intensity of the bioluminescence signal emitted from the lung cancer cells increased logarithmically during the course of study. Mice with positive bioluminescence signaling had confirmed tumors by microscopic histological analysis. Bioluminescence activity had a strong correlation with the tumor volume as determined histologically. Conclusions: Bioluminescence intensity directly correlates with tumor volume and therefore offers a reliable approach for detecting and monitoring the growth of human lung cancer cells in orthotopic murine models