Calcium efflux from the endoplasmic reticulum regulates cisplatin-induced apoptosis in human cervical cancer HeLa cells.

The function of calcium efflux from the endoplasmic reticulum (ER) in cisplatin-induced apoptosis is not fully understood in cancer cells. The present study used western blot analysis, flow cytometry, immunofluorescence and 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay to investigate calcium signaling in human cervical cancer cells exposed to cisplatin. In the present study, treatment with cisplatin increased free Ca2+ levels in the cytoplasm and mitochondria of human cervical cancer HeLa cells, which further triggers the mitochondria-mediated and ER stress-associated apoptosis pathways. Notably, blocking calcium signaling using the calcium chelating agent bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid acetoxymethyl ester inhibited cisplatin-induced apoptosis via downregulation of the calcium-dependent proteases, the calpains, and innate apoptosis proteins, such as caspsae-3, caspase-4 and C/EBP homologous protein (CHOP). In addition, use of the inositol triphosphate receptor inhibitor, 2-aminoethyl diphenylborinate, to inhibit calcium efflux from the ER resulted in similar effects. This data indicated that calcium efflux from the ER plays a significant role in cisplatin-induced apoptosis in human cervical cancer HeLa cells, which provides further mechanistic insights into the tumor cell-killing effect of cisplatin and potential therapeutic strategies to improve cisplatin chemotherapy.

Suppression of MAL gene expression is associated with colorectal cancer metastasis.

Mal, T-cell differentiation protein (MAL) is a candidate tumor suppressor gene that functions in membrane trafficking processes in polarized epithelial cells. The aim of the present study was to determine its clinical significance in colorectal cancer (CRC). The RNA and protein expression levels of MAL in 30 colorectal specimens were detected by semi-quantitative polymerase chain reaction and immunohistochemistry analysis. Statistical analysis was performed using SPSS software. The RNA level of MAL was significantly downregulated in the CRC tissues compared with the adjacent healthy tissue (P<0.05). MAL was only positively expressed in 20% of the CRC tissues, but in 66.7% of the adjacent tissues, as determined by immunohistochemistry analysis. The expression of the MAL RNA transcript exhibited a positive correlation with protein expression. The expression levels of MAL were significantly associated with different tumor-node-metastasis stages and lymph node metastasis (P<0.05), but not with age, gender, tumor site, differentiation status and pathological type (P>0.05). Suppression of MAL expression was significantly correlated with metastasis in CRC. The present study indicated that MAL may function as an anti-metastasis factor and represent a potential biomarker for malignant colorectal tumors.