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Background: Osteopontin (OPN) is associated with tumor formation, progression and metastasis, and increased OPN levels have been associated with poor survival in breast cancer. We investigated the mechanisms responsible for OPN activity, and the relationships between OPN expression and clinical parameters in breast cancer. Methods: OPN mRNA and protein levels were compared in malignant and benign breast tumors by polymerase chain reaction (PCR) and immunohistochemistry, respectively, and levels in breast cancer cells were determined by PCR and western blotting. The effects of lentiviral-mediated knockdown of OPN on OPN and αv,β3 integrin expression, cell invasion and migration, autophagy and apoptosis were analyzed in MDA-MB-231 cells. Results: OPN expression increased with aggressiveness of breast cancer phenotype. OPN knockdown inhibited αv,β3 integrin expression in MDA-MB-231 cells, with subsequent inhibition of cell migration and invasion. Knockdown also inhibited the PI3K/Akt/mTOR pathway, promoted expression of the autophagy-related gene products LC3 and Beclin 1, and increased apoptosis. OPN expression was positively associated with tumor grade and lymph node metastasis. Conclusion: These results suggest that knockdown of OPN may inhibit breast cancer metastasis by regulating αv,β3 integrin expression and inducing autophagy and subsequent inhibition of PI3K/Akt/mTOR signaling, thus providing further insights into the complex mechanisms regulating tumor growth and metastasis. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Docetaxel, a member of the taxane family, has been shown to induce apoptosis in a variety of cancer cells. However, toxicity at therapeutic doses has precluded the use of docetaxel alone for the management of cancer patients. PSK, a protein-bound polysaccharide, is widely used in Japan as an immunopotentiating biological response modifier for cancer patients. Our previous study showed that PSK induced downregulation of several invasion-related factors, suggesting an interaction of PSK with transcriptional factors. In this study, we showed that PSK dose dependently enhanced apoptosis induced by 1?nM of docetaxel in a human pancreatic cancer cell line NOR-P1. Furthermore, PSK inhibited docetaxel-induced nuclear factor kappa B (NF-?B) activation. Moreover, the expression of cellular inhibitor of apoptosis protein (cIAP-1), which is transcriptionally regulated by NF-?B and functions as an antiapoptotic molecule through interrupting the caspase pathway, was also inhibited by treatment with PSK plus docetaxel. As a result, PSK enhanced the docetaxel-induced caspase-3 activation. In addition, treatment by transfection of NF-?B decoy oligodeoxynucleotides (ODNs), but not scramble ones, inhibited the expression of cIAP-1 in NOR-P1 cells and induced a significant increase in docetaxel-induced apoptosis. Our data indicate that PSK suppresses the docetaxel-induced NF-?B activation pathway. Combination of PSK with a low dose of docetaxel may be a new therapeutic strategy to treat patients with pancreatic cancer.Oncogene (2003) 22, 2088-2096. doi:10.1038/sj.onc.1206310 [ABSTRACT FROM AUTHOR]

The unique and tailorable physicochemical features of zinc oxide nanoparticles (ZnO-NPs) synthesized from green sources make them attractive for use in cancer treatment. Hydroponic-cultured ginseng-root-synthesized ZnO-NPs (HGRCm-ZnO NPs) were coated with O-carboxymethyl chitosan (CMC) polymer, which stabilized and enhanced the biological efficacy of the nanoparticles. Nanoparticles were characterized by X-ray diffraction (XRD), UV-Vis spectroscopy, transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), and energy-dispersive X-ray spectroscopy (EDS). The flower-shaped nanoparticles were crystalline in nature with a particle size of 28 nm. To evaluate if these NPs had anti-lung cancer activity, analysis was performed on a human lung carcinoma cell line (A549). HGRCm-ZnO nanoparticles showed less toxicity to normal keratinocytes (HaCaTs), at concentrations up to 20 µg/mL, than A549 cancer cells. Additionally, these NPs showed dose-dependent colony formation and cell migration inhibition ability, which makes them more promising for lung cancer treatment. Additionally, Hoechst and propidium iodide dye staining also confirmed that the NP formulation had apoptotic activity in cancer cells. Further, to evaluate the mechanism of cancer cell death via checking the gene expression, HGRCm ZnO NPs upregulated the BAX and Caspase 3 and 9 expression levels but downregulated Bcl-2 expression, indicating that the nanoformulation induced mitochondrial-mediated apoptosis. Moreover, these preliminary results suggest that HGRCm ZnO NPs can be a potential candidate for future lung cancer treatment. [ABSTRACT FROM AUTHOR]

The detailed regulatory mechanism of LINC00174 in lung cancer (LC) development remains largely unknown. This research was designed to probe into the impacts of LINC00174 in LC cells through modulating the microRNA (miR)-584-3p/ribosomal protein S24 (RPS24) axis. LINC00174, miR-584-3p, and RPS24 expression levels in LC cells and tissues were examined. The constructs altering LINC00174, miR-584-3p, or RPS24 expression were transfected into LC cells to examine the malignant phenotypes of LC cells. The relations among LINC00174, miR-584-3p, and RPS24 were validated. LINC00174 and RPS24 were high-expressed while miR-584-3p was low-expressed in LC. Downregulated LINC00174 or RPS24 or upregulated miR-584-3p inhibited the malignant biological behaviors of LC cells. The silenced miR-584-3p could reverse the repressive effects of reduced LINC00174 on the development of LC cells; while RPS24 overexpression inverted the repressive effects of miR-584-3p elevation on LC cells. Mechanically, LINC00174 bound to miR-584-3p that targeted RPS24. Repressed LINC00174 can relieve the malignant phenotypes of LC cells via modulating the miR-584-3p/RPS24 axis. [ABSTRACT FROM AUTHOR]

Isaindigotone is an alkaloid containing a pyrrolo-[2,1-b]quinazoline moiety conjugated with a benzylidene group and isolated from the root of Isatis indigotca Fort. However, further anticancer activities of this alkaloid and its derivatives have not been fully explored. In this work, a novel isaindigotone derivative was synthesized and three different gastric cell lines and one human epithelial gastric cell line were used to study the anti-proliferation effects of the novel isaindigotone derivative BLG26. HGC27 cells and AGS cells were used to further explore the potential mechanisms. BLG26 exhibited better anti-proliferation activities in AGS cells with a half-maximal inhibitory concentration (IC50) of 1.45 μM. BLG26 caused mitochondrial membrane potential loss and induced apoptosis in both HGC27 cells and AGS cells by suppressing mitochondrial apoptotic pathway and PI3K/AKT/mTOR axis. Acute toxicity experiment showed that LD50 (median lethal dose) of BLG26 was above 1000.0 mg/kg. This research suggested that BLG26 can be a potential candidate for the treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

Abstract: Micro-RNAs (miRNAs) have been found to be implicated in a very wide range of physiological processes. This study was aimed to investigate the regulation of miRNA-429 (miR-429) in gastric cancer cells on cell proliferation and apoptosis. Quantitative PCR was employed to detect the expressions of miR-429 after eukaryotic expression plasmid of miR-429 and its inhibitor were transiently transfected into poorly differentiated human gastric cancer cell line BGC823. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction as-says were used to examine proliferation ability. Apoptosis was analyzed by flow cytometry after transfection. The results showed that 48 h after transfection, overexpression of miR-429 reached maximum efficiency. Compared with mock transfection, miR-429 inhibited tumor cell proliferation significantly (P < 0.05) at 48 h and 72 h. of Overexpression of miR-429 promoted tumor cell apoptosis when compared with mock transfected cells (P < 0.05). On the contrary, miR-429 inhibitor promoted tumor cell proliferation and inhibited apoptosis when compared with controls (P < 0.05). Our results suggested that miRNA-429 may serve as a tumor suppressor during tumorigenesis of gastric cancer and may be a potential gastric cancer therapeutic target. [Copyright &y& Elsevier]

Conjugated linolenic acid (CLNA) is a type of ω-3 fatty acid which has been proven to have a series of benefits. However, there is no study about the function of Lactobacillus-derived CLNA isomer. Lactobacillus plantarum ZS2058 has been proven to manifest comprehensive functions and can produce CLNA. To investigate the specific functions of CLNA produced by this probiotic bacterium, two different conjugated α-linolenic acid (CLNA) isomers were successfully isolated. These isoforms, CLNA1 (c9, t11, c15-CLNA, purity 97.48%) and CLNA2 (c9, t11, t15-CLNA, purity 99.00%), both showed the ability to inhibit the growth of three types of colon cancer cells in a time- and concentration-dependent manner. In addition, the expression of MDA in Caco-2 cells was increased by CLNA1 or CLNA2, which indicated that lipid peroxidation was related to the antiproliferation activity of CLNAs. An examination of the key protein of pyroptosis showed that CLNA1 induced the cleavage of caspase-1 and gasdermin-D, while CLNA2 induced the cleavage of caspase-4, 5 and gasdermin-D. The addition of relative inhibitors could alleviate the pyroptosis by CLNAs. CLNA1 and CLNA2 showed no effect on caspase-3, 7, 9 and PARP-1, which were key proteins associated with apoptosis. No sub-diploid apoptotic peak appeared in the result of PI single staining test. In conclusion, CLNA1 activated caspase-1 and induced Caco-2 cell pyroptosis, whereas CLNA2 induced pyroptosis through the caspase-4/5-mediated pathway. The inhibition of Caco-2 cells by the two isomers was not related to apoptosis. This is the first study on the function of Lactobacillus-derived CLNA isomer. The inhibition pathway of Lactobacillus-derived CLNA isomer on colon cancer cells were proved. [ABSTRACT FROM AUTHOR]