The reversibility of non-genotoxic phenotypic changes has been explored in order to develop novel preventive and therapeutic approaches for cancer. Quisinostat (JNJ-26481585), a novel second-generation histone deacetylase inhibitor (HDACi), has efficient therapeutic actions on non-small cell lung cancer (NSCLC) cell. The present study aims at investigating underlying molecular mechanisms involved in the therapeutic activity of quisinostat on NSCLC cells. We found that quisinostat significantly inhibited A549 cell proliferation in dose- and time-dependent manners. Up-acetylation of histones H3 and H4 and non-histone protein α-tubulin was induced by quisinostat treatment in a nanomolar concentration. We also demonstrated that quisinostat increased reactive oxygen species (ROS) production and destroyed mitochondrial membrane potential (ΔΨm), inducing mitochondria-mediated cell apoptosis. Furthermore, exposure of A549 cells to quisinostat significantly suppressed cell migration by inhibiting epithelial-mesenchymal transition (EMT) process. Bioinformatics analysis indicated that effects of quisinostat on NSCLC cells were associated with activated p53 signaling pathway. We found that quisinostat increased p53 acetylation at K382/K373 sites, upregulated the expression of p21(Waf1/Cip1), and resulted in G1 phase arrest. Thus, our results suggest that the histone deacetylase can be a therapeutic target of NSCLC to discover and develop a new category of therapy for lung cancer.Electronic supplementary materialThe online version of this article (doi:10.1007/s10565-016-9347-8) contains supplementary material, which is available to authorized users.

The drug resistance and tumor metastasis have been the main obstacles for the longer-term therapeutic effects of tamoxifen (TAM) on estrogen receptor-positive (ER) breast cancer, but the mechanisms underlying the TAM resistance are still unclear. Here, we demonstrated that the membrane-associated estrogen receptor ER-α36 signaling, but not the G protein-coupled estrogen receptor 1 (GPER1) signaling, might be involved in the TAM resistance and metastasis of breast cancer cells. In this study, a model of ER breast cancer cell MCF-7 that involves the up-regulated expression of ER-α36 and unchanged expression of ER-α66 and GPER1 was established via the removal of insulin from the cell culture medium. The mechanism of TAM resistance in the ER breast cancer cell line MCF-7 was investigated, and the results showed that the stimulating effect of insulin on susceptibility of MCF-7 to TAM was mediated by ER-α36 and that the expression level of ER-α36 in TAM-resistant MCF-7 cells was also significantly increased. Both TAM and estradiol (E2) could promote the migration of triple negative (ER-α66/PR/HER2) and ER-α36/GPER1 breast cancer cells MDA-MB-231. The migration of MDA-MB-231 cells was inhibited by the down-regulated intracellular expression of ER-α36 by transient transfection of specific small interfering RNA, whereas no effect of GPER1 down-regulation was observed. Meanwhile, the effect of TAM on the migration of ER-α36-down-regulated MDA-MB-231 cells was also reduced. Furthermore, it was found that TAM enhanced the distribution of integrin β1 on the cell surface but did not affect the expression of integrin β1 in MDA-MB-231 cells. Collectively, these data suggested that ER-α36 signaling might play critical roles in acquired and de novo TAM resistance and metastasis of breast cancer, and ER-α36 might present a potential biomarker of TAM resistance in the clinical diagnosis and treatment of ER breast cancer.

RALT approach for LAM resection can be performed safely with favorable cosmetic outcome, accepted clinical results, and lower cost. It should be considered as a promising alternative to SMS and merit additional study.

Lung cancer is one of the most common malignancies worldwide. The present study aimed to investigate specific genotypes of different subtypes or stages of lung cancer through gene expression variations of chromosome 2 genes, trying to identify predictors for diagnosis or prognosis of lung cancer. About 537 patients with lung adenocarcinoma (ADC), 140 patients with lung squamous carcinoma (SQC), 9 patients with lung large cell carcinoma (LCC), 56 patients with small cell lung cancer (SCLC), and 590 patients without cancer were analyzed in present study. Co-expressed, subtype-specific, and stage-specific chromosome 2 genes were identified and further analyzed by bioinformatic methods. As a result, 15 or 10 genes were significantly up- or down-regulated in all four subtypes of lung cancer. GKN1, LOC100131510, prominin-2 (PROM2), IL37, and SNORA41 were identified as ADC-specific up-regulated genes; SQC-specific up-regulated genes included HOXD family (HOXD1, HOXD3, HOXD4, HOXD8, and HOXD9) and UGT1A family (UGT1A1, UGT1A3, UGT1A4, UGT1A5, UGT1A7, UGT1A8, UGT1A9, and UGT1A10); and LCC- or SCLC-specific genes were also identified. Nine genes were significantly up-expressed at all four stages of ADC while 230 genes at all three stages of SQC. MFSD2B, CCL20 and STAT1, or STARD7 and ZNF512 genes may be risk or protect factors in prognosis of ADC, while HTR2B, DPP4, and TGFBRAP1 genes may be risk factors in prognosis of SQC. Our results suggested that a number of altered chromosome 2 genes have the subtype or stage specificities of lung cancer and may be considered as diagnostic and prognostic biomarkers.