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Proliferation and metastasis are significantly malignant characteristics of human lung cancer, but the underlying molecular mechanisms are poorly understood. Chromobox 4 (CBX4), a member of the Polycomb group (PcG) family of epigenetic regulatory factors, enhances cellular proliferation and promotes cancer cell migration. However, the effect of CBX4 in the progression of lung cancer is not fully understood. We found that CBX4 is highly expressed in lung tumours compared with adjacent normal tissues. Overexpression of CBX4 significantly promotes cell proliferation and migration in human lung cancer cell lines. The knockdown of CBX4 obviously suppresses the cell growth and migration of human lung cancer cells in vitro. Also, the proliferation and metastasis in vivo are blocked by CBX4 knockdown. Furthermore, CBX4 knockdown effectively arrests cell cycle at the G0/G1 phase through suppressing the expression of CDK2 and Cyclin E and decreases the formation of filopodia through suppressing MMP2, MMP9 and CXCR4. Additionally, CBX4 promotes proliferation and metastasis via regulating the expression of BMI‐1 which is a significant regulator of proliferation and migration in lung cancer cells. Taken together, these data suggest that CBX4 is not only a novel prognostic marker but also may be a potential therapeutic target in lung cancer. [ABSTRACT FROM AUTHOR]

Abstract: IR‐783 is a kind of heptamethine cyanine dye that exhibits imaging, cancer targeting and anticancer properties. A previous study reported that its imaging and targeting properties were related to mitochondria. However, the molecular mechanism behind the anticancer activity of IR‐783 has not been well demonstrated. In this study, we showed that IR‐783 inhibits cell viability and induces mitochondrial apoptosis in human breast cancer cells. Exposure of MDA‐MB‐231 cells to IR‐783 resulted in the loss of mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) depletion, mitochondrial permeability transition pore (mPTP) opening and cytochrome c (Cyto C) release. Furthermore, we found that IR‐783 induced dynamin‐related protein 1 (Drp1) translocation from the cytosol to the mitochondria, increased the expression of mitochondrial fission proteins mitochondrial fission factor (MFF) and fission‐1 (Fis1), and decreased the expression of mitochondrial fusion proteins mitofusin1 (Mfn1) and optic atrophy 1 (OPA1). Moreover, knockdown of Drp1 markedly blocked IR‐783‐mediated mitochondrial fission, loss of MMP, ATP depletion, mPTP opening and apoptosis. Our in vivo study confirmed that IR‐783 markedly inhibited tumour growth and induced apoptosis in an MDA‐MB‐231 xenograft model in association with the mitochondrial translocation of Drp1. Taken together, these findings suggest that IR‐783 induces apoptosis in human breast cancer cells by increasing Drp1‐mediated mitochondrial fission. Our study uncovered the molecular mechanism of the anti‐breast cancer effects of IR‐783 and provided novel perspectives for the application of IR‐783 in the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Cu 2- x Se nanoparticles (Cu 2- x Se NPs) are widely used for optical diagnostic imaging and photothermal therapy due to their strong near-infrared (NIR) optical absorption. With the continuous expansion of applications using Cu 2- x Se NPs, their biosafety has received increasing attention in recent years. Cu 2- x Se NPs can enter the brain by crossing the blood-brain barrier, but the neurotoxicity of NPs remains unclear. The present investigation provides direct evidence that the toxicity of Cu 2- x Se NPs can be specifically exploited to kill rat pheochromocytoma PC-12 cells (a cell line used as an in vitro model for brain neuron research) in dose- and time-dependent manners. These cytotoxicity events were accompanied by mitochondrial damage, adenosine triphosphate (ATP) depletion, production of oxidizing species (including reactive oxygen species (ROS), malondialdehyde (MDA) and hydrogen peroxide (H 2 O 2 )), as well as reductions in antioxidant defense systems (glutathione (GSH) and superoxide dismutase (SOD)). Moreover, our in vivo study also confirmed that Cu 2- x Se NPs markedly induced neurotoxicity and oxidative stress damage in the striatum and hippocampal tissues of BALB/c mice. These findings suggest that Cu 2- x Se NPs induce neurotoxicity in PC-12 cells and BALB/c mice via oxidative stress damage, which provides useful information for understanding the neurotoxicity of Cu 2- x Se NPs., Competing Interests: The authors report no conflicts of interest related to this work., (This journal is © The Royal Society of Chemistry.)