Abstract
BackgroundGenipin is a compound derived from gardenia fruit extract. Although Genipin has anti-tumor effects in various cancers, its effect and mechanism in gastric cancer remain unclear. Here, we investigated the relationship between the anticancer effect of Genipin and signal transducer and activator of transcription (Stat3)/myeloid cell leukemia-1 (Mcl-1) in human gastric cancers.MethodsMTT assays were performed to determine the cell viability of gastric cancer and gastric epithelial cell lines (AGS, MKN45, SNU638, MKN74, HFE-145). A TUNEL assay and Western blotting were carried out to investigate apoptosis. Stat3 activity was measured by proteome profiler phospho kinase array, immunofluorescence and immunoblotting. Mitochondria function was monitored with an XF24 analyzer and by flow cytometry, confocal microscopy using fluorescent probes for general mitochondrial membrane potential (MMP).ResultsGenipin induced apoptosis in gastric cancer cells, including AGS and MKN45 cells. Genipin also reduced Mcl-1 mRNA and protein levels. Furthermore, we found that phosphorylation of Stat3 is regulated by Genipin. Additionally, the protein level of phospho Janus kinase 2 (JAK2) was decreased by Genipin treatment, indicating that the Stat3/JAK2/Mcl-1 pathway is suppressed by Genipin treatment in gastric cancer cells. Mcl-1 is closely related to mitochondrial function. These findings suggest that Genipin contributes to the collapse of mitochondrial functions like MMP.ConclusionsGenipin induced apoptosis by suppressing the Stat3/Mcl-1 pathway and led to mitochondrial dysfunction. Our results reveal a novel mechanism for the anti-cancer effect of Genipin in gastric cancer.
Highlights
IntroductionGenipin has anti-tumor effects in various cancers, its effect and mechanism in gastric cancer remain unclear
Genipin is a compound derived from gardenia fruit extract
Genipin mediates apoptosis by downregulating mcl-1 We detected the expression levels of pro-and anti-apoptotic proteins by western blot analysis in AGS cells to investigate whether Genipin regulates apoptotic proteins
Summary
Genipin has anti-tumor effects in various cancers, its effect and mechanism in gastric cancer remain unclear. We investigated the relationship between the anticancer effect of Genipin and signal transducer and activator of transcription (Stat3)/myeloid cell leukemia-1 (Mcl-1) in human gastric cancers. Cancer is a major cause of human death, and chemotherapy drugs have been developed to improve the survival rate of patients with cancer, but these drugs show various side effects. The main strategy in cancer therapy involving chemotherapy drugs is to induce apoptotic cell death [1]. The Janus kinase (JAK)/signal transducer and activator of transcription (Stat) signaling regulates various processes such as cell growth, survival, angiogenesis, and immunity and are activated by growth factors and cytokines [6, 7].
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