title: Black Currant (Ribes nigrum L.) Extract Induces Apoptosis of MKN-45 and TE-1 Cells Through MAPK- and PI3K/Akt-Mediated Mitochondrial Pathways.
abstract: Black currant extract (BCE) is rich in polyphenols and can induce apoptosis in various cancer cells, but the molecular mechanism by which BCE induces cancer cell apoptosis has not been reported. The aim of this work was to elucidate the antitumor effect of BCE and the signal transduction pathways involved. MTT test results revealed that the viability of MKN-45 and TE-1 cells treated with BCE gradually decreased in a concentration-dependent manner, with significant effects achieved after 12 h of treatment. MKN-45 and TE-1 cells clearly showed characteristics of apoptosis: shrinkage, cytoplasmic condensation, and formation of cytoplasmic filaments, even partial detachment. In addition, these results showed MKN-45 cells showed a higher level of apoptosis than TE-1 cells when treated with BCE. Western blot assays showed that the Bcl-2/Bax ratio decreased in both MKN-45 and TE-1 cells, indicating that BCE induced apoptosis through the mitochondrial pathway. In addition, BCE-induced apoptosis was mediated by mitochondrial dysfunction involving the PI3K/Akt pathway in both MKN-45 and TE-1 cells. However, BCE-induced cell apoptosis was mediated by the Fas receptor pathway in MKN-45 cells but not in TE-1 cells. BCE-induced apoptosis in MKN-45 cells was associated with the MAP-kinase signaling pathway through the activation of p38 and JNK and the inactivation of Erk1/2. However, it was associated with the MAP-kinase signaling pathway only by means of activation of p38 and JNK in TE-1 cells. These results showed that BCE induces apoptosis of MKN-45 and TE-1 cells through MAPK- and PI3K/Akt-mediated mitochondrial pathways. Thus, BCE may be a promising anticancer candidate.
authors.affiliation: The Affiliated Tumor Hospital of Harbin Medical University , Harbin, China .
authors.forename: Bingshuo
authors.initials: B
authors.lastname: Liu
authors.affiliation: The Affiliated Tumor Hospital of Harbin Medical University , Harbin, China .
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D010936:Plant Extracts; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3
keywords: MKN-45 cells; TE-1 cells; apoptosis; black currant extract