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12 September 2019 : Laboratory Research  

Inhibition of Proliferation of SGC7901 and BGC823 Human Gastric Cancer Cells by Ursolic Acid Occurs Through a Caspase-Dependent Apoptotic Pathway

Jing Zhang1BCD, Fengjun Liu2CDEF, Xin Zhang2ABEF*

DOI: 10.12659/MSM.916740

Med Sci Monit 2019; 25:6846-6854

Abstract

BACKGROUND: Worldwide, gastric cancer is one of the most common malignant tumors. Ursolic acid is a plant metabolite and pentacyclic triterpenoid used in traditional Chinese medicine. This study aimed to investigate the effects of ursolic acid the growth and apoptosis of SGC7901 and BGC823 human gastric cancer cells in vitro.

MATERIAL AND METHODS: SGC7901 and BGC823 human gastric cancer cells and normal GES-1 gastric epithelial cells were cultured with increasing doses of ursolic acid at 50, 60, and 100 µM. Cell viability and proliferation were assessed using an MTT assay. Flow cytometry was used to assess cell apoptosis. Western blot was used to measure procaspase-8, procaspase-9, procaspase-3, and cleaved poly (ADP-ribose) polymerase (PARP) expression. The expression of receptor interaction protein 3 (RIP3) was examined by Western blot and reverse transcription polymerase chain reaction (RT-PCR). Morphological changes in the gastric cancer cells were determined using Hoechst 33342 staining following ursolic acid treatment.

RESULTS: Ursolic acid inhibited the viability of SGC7901 and BGC823 cells but not GES-1 cells. Ursolic acid treatment significantly induced apoptosis in SGC7901 and BGC823 cells when compared with GES-1 cells (P<0.05), and significantly increased the activation of caspase-3, caspase-8, caspase-9, poly ADPribose polymerase (PARP), and the production of reactive oxygen species (ROS). Treatment of SGC7901 and BGC823 cells with ursolic acid for 72 h did not induce necroptosis.

CONCLUSIONS: Ursolic acid inhibited the proliferation of SGC7901 and BGC823 human gastric cancer cells in vitro through a caspase-dependent apoptotic pathway.

Keywords: Antineoplastic Agents, Apoptosis, Caspase 12, Triterpenes, Caspase 3, Caspase 8, Caspase 9, Cell Survival, China, Poly (ADP-Ribose) Polymerase-1, Receptor-Interacting Protein Serine-Threonine Kinases, Stomach Neoplasms

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750