IntroductionThe existence of breast cancer stem-like cells (BCSCs) has profound implications for cancer prevention. Genistein, a predominant isoflavone found in soy products, has multiple robust anti-tumor effects in various cancers, especially in the breast and prostate cancer. In this study, we aimed to evaluate genistein inhibition of BCSCs and its potential mechanism by culturing MCF-7 breast cancer cells and implanting these cells into nude mice.MethodsCell counting, colony formation and cell apoptosis analysis were used to evaluate the effect of genistein on breast cancer cells’ growth, proliferation and apoptosis. We then used mammosphere formation assay and CD44CD24 staining to evaluate the effect of genistein on BCSCs in vitro. A nude mice xenograft model was employed to determine whether genistein could target BCSCs in vivo, as assessed by real-time polymerase chain reaction (PCR) and immunohistochemical staining. The potential mechanism was investigated utilizing real-time PCR, western blotting analysis and immunohistochemical staining.ResultsGenistein inhibited the MCF-7 breast cancer cells’ growth and proliferation and promoted apoptosis. Both in vitro and in vivo genistein decreased breast cancer stem cells, and inhibited breast cancer stem-like cells through down-regulation of the Hedgehog-Gli1 Signaling Pathway.ConclusionsWe demonstrated for the first time that genistein inhibits BCSCs by down-regulating Hedgehog-Gli1 signaling pathway. These findings provide support and rationale for investigating the clinical application of genistein in treating breast cancer, and specifically by targeting breast cancer stem cells.

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Colorectal cancer (CRC) is reported to be the third and fourth, most diagnosed and cause of cancer associated deaths respectively. In 2012 for instance, about 1.4 million new cases were reported, and approximately 700,000 deaths recorded. Survival from CRC is dependent on the stage at which it is diagnosed coupled with appropriate surgical and medical intervention. Cisatracurium is widely used for skeletal muscle relaxation during abdominal surgeries, including bowel and colon surgeries. Recent studies reported that cisatracurium inhibits progression of human cancer cells, however, the mechanisms leading to the inhibition are yet to be completely understood. To elucidate mechanisms resulting particularly in tumor cell growth and metastasis, we developed ex vivo and in in vivo xenograft models of CRC. Cisatracurium caused upregulation of p53 and its down-stream genes and proteins known to regulate proliferation and metastasis in vitro and in vivo. Genomic analyses of CRC following cisatracurium treatment revealed moderate to high DNA damage, while functional analyses demonstrated significant tumor cells growth regression, as well as repression of migration and invasion. Importantly, cisatracurium increased E-Cadherin and CALD-1 but decreased SNAI-1 and SLUG levels in vitro and in vivo. Together, the findings demonstrate that elevation of p53 upon cisatracurium-induced genomic injury, represent a potential mechanism by which cisatracurium result in the suppression of CRC progression and metastasis.

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