The Ubiquitin Gene Expression Pattern and Sensitivity to UBB and UBC Knockdown Differentiate Primary 23132/87 and Metastatic MKN45 Gastric Cancer Cells

Gastric cancer (GC) is one of the most common and lethal cancers. Alterations in the ubiquitin (Ub) system play key roles in the carcinogenetic process and in metastasis development. Overexpression of transcription factors YY1, HSF1 and SP1, known to regulate Ub gene expression, is a predictor of poor prognosis and shorter survival in several cancers. In this study, we compared a primary (23132/87) and a metastatic (MKN45) GC cell line. We found a statistically significant higher expression of three out of four Ub coding genes, UBC, UBB and RPS27A, in MKN45 compared to 23132/87. However, while the total Ub protein content and the distribution of Ub between the conjugated and free pools were similar in these two GC cell lines, the proteasome activity was higher in MKN45. Ub gene expression was not affected upon YY1, HSF1 or SP1 small interfering RNA (siRNA) transfection, in both 23132/87 and MKN45 cell lines. Interestingly, the simultaneous knockdown of UBB and UBC mRNAs reduced the Ub content in both cell lines, but was more critical in the primary GC cell line 23132/87, causing a reduction in cell viability due to apoptosis induction and a decrease in the oncoprotein and metastatization marker β-catenin levels. Our results identify UBB and UBC as pro-survival genes in primary gastric adenocarcinoma 23132/87 cells.

Design, Synthesis, and Biological Evaluation of Novel Nitrogen Heterocycle-Containing Ursolic Acid Analogs as Antitumor Agents

Nineteen ursolic acid analogues were designed, synthesized, and evaluated for their antiproliferative activity against the Hela and MKN45 cell lines. Some compounds containing a piperazine moiety displayed moderate to high levels of antitumor activities against the tested cancer cell lines. The most potent compound shares the IC50 value of 2.1 µM and 2.6 µM for the Hela and MKN45 cell lines, respectively. Further mechanism studies and in vivo antitumor studies have shown that it decreased the apoptosis regulator (BCL2/BAX) ratio, disrupted mitochondrial potential and induced apoptosis, and suppressed the growth of Hela xenografts in nude mice.

Antiproliferatif Ekstrak Metanol Daun Dianella nemorosa Lam. (Liliaceae) terhadap Sel Kanker MKN45 dengan Menggunakan Metode WST-1

Dianella nemorosa Lam. was known containing alkaloids, terpenoid, phenolic compouds and tanin. Antiproliferative effect of D. nemorosa leaves methanol exctract, which demonstrated to have an in vitro cytotoxic effect on cancer cell line. The aim of research was examined the effect antiproliferative methanol extract of D. nemorosa leaves against MKN45 (gastric cancer) cell line. Leaves powder extracted using methanol. Antiproliferative effect was determined by Cell Proliferation Reagents WST-1 ((2-(4-iodophenyl)-3-(4-nitro-phenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt). Test for 1h, 2h, and 4h after incubated for 72h was done. The result of this research showed that methanol exctract from D. nemorosa possessed remarkable no had antiproliferative activity against MKN45 cell line. The result indicated methanol extract of D. nemorosa leaves selective inhibitory effect or antiproliferative against cell line. Key words: Dianella nemorosa, Antiproliferative, MKN 45, and WST-1