LINC00152 knock-down suppresses esophageal cancer by EGFR signaling pathway

AimThis study aims to explain the role and mechanism of lncRNA LINC00152 in esophageal cancer.MethodsThe 30 pairs of esophageal cancer and adjacent normal tissues were collected and measuring the lncRNA LINC00152 expression by ISH and RT-qPCR assay. In the next cell experiment, Eca 109 and Kyse 150 cells were divided into 3 groups: NC group were treated with non-treatment; BL group were transfected with empty vector and lncRNA group were transfected with lncRNA LINC00152. The cells proliferation were measured by MTT assay; the cells apoptosis and cell cycle were evaluated by flow cytometry. The relative proteins expressions were measured by WB assay.ResultsCompared with NC groups, the cell proliferation rate of lncRNA groups were significantly suppressed (P<0.05, respectively); the cell apoptosis and G1 phase rates were significantly enhanced in the lncRNA groups (P<0.05, respectively). In the proteins expressions, the EGFR, PI3K and AKT proteins expressions of lncRNA group were significantly inhibited and the P21 proteins expressions were significantly stimulated in the lncRNA groups compared with those of NC groups in Eca 109 and Kyse 150 cells.ConclusionThe lncRNA LINC00152 had anti-tumor effects on esophageal cancer in the Eca 109 and Kyse 150 cells, the mechanisms were relative with EGFR pathway.

Effect of new olivacine derivatives on p53 protein level

Background The p53 protein is a transcription factor for many genes, including genes involved in inhibiting cell proliferation and inducing apoptosis in genotoxically damaged and tumor-transformed cells. In more than 55% of cases of human cancers, loss of the essential function of p53 protein is found. In numerous reports, it has been shown that small molecules (chemical compounds) can restore the suppressor function of the mutant p53 protein in tumor cells. The aim of this study was to evaluate the potential anticancer activity of three newly synthesized olivacine derivatives. Methods The study was performed using two cell lines—CCRF/CEM (containing the mutant p53 protein) and A549 (containing a non-mutant, wild-type p53 protein). The cells were incubated with olivacine derivatives for 18 h and then assays were carried out: measurement of the amount of p53 and p21 proteins, detection of apoptosis, cell cycle analysis, and rhodamine 123 accumulation assay (evaluation of P-glycoprotein inhibition). Multiple-criteria decision analysis was used to compare the anticancer activity of the tested compounds. Results Each tested compound caused the reconstitution of suppressor activity of the p53 protein in cells with the mutant protein. In addition, one of the compounds showed significant antitumor activity in both wild-type and mutant cells. For all compounds, a stronger effect on the level of the p53 protein was observed than for the reference compound—ellipticine. Conclusions The observed effects of the tested new olivacine derivatives (pyridocarbazoles) suggest that they are good candidates for new anticancer drugs.

XRRA1 Targets ATM/CHK1/2-Mediated DNA Repair in Colorectal Cancer

X-ray radiation resistance associated 1 (XRRA1) has been found to regulate the response of human tumor and normal cells to X-radiation (XR). Although XRRA1 overexpression is known to be involved in cancer cell response to XR, there are no reports about whether the expression of XRRA1 in tumors can adjust radioresistance. It is widely known that cell cycle arrest could cause radioresistance. We found that blocked XRRA1 expression could lead to cell cycle G2/M arrest by the regulation of cyclin A, cyclin E, and p21 proteins in colorectal cancer (CRC) and expression of XRRA1 reduced cell cycle arrest and increased cell proliferation in CRC. However, whether regulation of the cell cycle by XRRA1 can influence radioresistance is poorly characterized. Correspondingly, DNA repair can effectively lead to radioresistance. In our study, when cancer cells were exposed to drugs and ionizing radiation, low expression of XRRA1 could increase the phosphorylation of DNA repair pathway factors CHK1, CHK2, and ATM and reduce the expression of γ-H2AX, which is believed to participate in DNA repair in the nucleus. Crucially, our results identify a novel link between XRRA1 and the ATM/CHK1/2 pathway and suggest that XRRA1 is involved in a DNA damage response that drives radio- and chemoresistance by regulating the ATM/CHK1/2 pathway.

Anticancer Activity of Marine SpongeHyrtiossp. Extract in Human Colorectal Carcinoma RKO Cells with Different p53 Status

Drug development using marine bioresources is limited even though the ocean occupies about 70% of the earth and contains a large number of biological materials. From the screening test of the marine sponge extracts, we foundHyrtiossp. sponge collected from Chuuk island, Micronesia. In this study, theHyrtiossp. extract was examined for anticancer activity against human colorectal carcinoma RKO cells that are wildtype for p53 and RKO-E6 that are p53 defective. TheHyrtiossp. extract dose-dependently inhibited viability in both cell lines. Multinucleation as an indication of mitotic catastrophe was also observed. Cytotoxicity tests gave significantly different results for RKO and RKO-E6 cells after 48 h exposure toHyrtiossp. extract. In RKO cells treated withHyrtiossp. extract, cell death occurred by induction of p53 and p21 proteins. In p53-defective RKO-E6 cells,Hyrtiossp. extract decreased expression of JNK protein and increased p21 protein. These results indicate thatHyrtiossp. extract induced apoptosisviadifferent pathways depending on p53 status and could be a good natural product for developing new anticancer drugs.