Abstract
BackgroundCostunolide, a sesquiterpene lactone extracted from Radix Aucklandiae, has the activity against multiple cancers. However, the effect of costunolide on gastric cancer (GC) have remained to be ambiguous. In this study, we investigated the underlying mechanisms of apoptosis induced by costunolide in human gastric adenocarcinoma BGC-823 cells in vitro and in vivo.MethodsThe viability of BGC-823 cells was detected by MTT assay. The apoptosis and mitochondrial membrane potential (ΔΨm) of BGC-823 cells induced by costunolide were analyzed by flow cytometry. The inhibiton of costunolide on human gastric adenocarcinoma was estimated in xenografts in nude mice. Apoptosis related proteins and genes were detected by Western blot and Q-PCR.ResultsCostunolide inhibited the viability of BGC-823 cells in a time and concentration dependent manner. Costunolide induced the apoptosis and lowered the ΔΨm of BGC-823 cells significantly. Costunolide increased the expression of Bax, cleaved caspase 9, cleaved caspase 7, cleaved caspase 3 and cleaved poly ADP ribose polymerase (PARP) proteins and decreased the expression of Bcl-2, pro-caspase 9, pro-caspase 7, pro-caspase 3 and PARP proteins. Costunolide upregulated the expression of puma, Bak1 and Bax mRNA and downregulated the expression of Bcl-2 mRNA. In addition, we demonstrated that costunolide inhibited the growth and induced apoptosis of BGC-823 cells xenografted in athymic nude mice. Costunolide increased the expression of cleaved caspase 9, cleaved caspase 3 and Bax proteins and decreased the expression of Bcl-2 protein in xenografted tumor. Costunolide upregulated the expression of puma and Bax mRNA and decreased the expression of Bcl-2 mRNA in xenografted tumor.ConclusionsCollectively, our results suggested that costunolide induced mitochondria-mediated apoptosis in human gastric adenocarcinoma BGC-823 cells and could be the candidate drug against GC in clinical practice.
Highlights
Costunolide, a sesquiterpene lactone extracted from Radix Aucklandiae, has the activity against multiple cancers
Costunolide inhibited the viability of gastric adenocarcinoma BGC-823 cells The purity of costunolide was measured by High-performance liquid chromatography (HPLC) in order to ensure the quality and accuracy of experiments
Costunolide induced the apoptosis of gastric adenocarcinoma BGC-823 cells According to the results of MTT assay, costunolide inhibited the viability of gastric cancer cells, we further study whether costunolide induced the apoptosis of BGC-823 cells
Summary
Costunolide, a sesquiterpene lactone extracted from Radix Aucklandiae, has the activity against multiple cancers. The effect of costunolide on gastric cancer (GC) have remained to be ambiguous. We investigated the underlying mechanisms of apoptosis induced by costunolide in human gastric adenocarcinoma BGC-823 cells in vitro and in vivo. The pathogenesis of GC is a complex and long-time multistep process, which is closely related to abnormal expression of many genes. The treatment for GC contains surgery, chemotherapy, Apoptosis is a process of programmed cell death and plays an important role in regulation of organ development and tissue carcinogenesis [5]. The pathogenesis of GC is closely related to abnormal apoptosis of gastric gland cells. Previous reports showed that inducing apoptosis of cancer cells is the critical method of treatment of GC [6].
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