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- Title
Proapoptotic and Growth-inhibitory Effects of Plumbagin on Human Gastric Cancer Cells Via Suppression of Signal Transducer and Activator of Transcription 3 and Protein Kinase B.
- Authors
Jing Li; Jia Li; Guowei Cai; Lin Shen; Furong Lu
- Abstract
Context • Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related deaths in the world. The current treatments include surgery and chemotherapy, either alone or in combination with radiotherapy, but the prognosis for patients with GC is usually poor. A safe and effective chemopreventive treatment for this malignant disease is urgently needed. Objective • The study intended to investigate the effects and underlying mechanisms of plumbagin, a quinonoid constituent that is derived from the roots of the medicinal plant Plumbago zeylanica, which exhibits potent anticancer properties against a number of cancers. Design • The in vitro study used the human GC cell line SGC-7901. Setting • All experiments were conducted at the Hubei University of Chinese Medicine and Tongji Medical College, Huazhong University of Science and Technology (Wuhan, China). Intervention • SGC-7901 cells were cultured in 30-mm dishes and treated with plumbagin at concentrations of 0, 5, 10, to 20 μmol/L. The cells were incubated with 10 μmol/L plumbagin for different amounts of time (0, 2, 4, 8, 12, and 24 h) in contact with the cancer cells. Outcome Measures • The cell viability was examined using a cell counting kit-8 viability assay, and the cell proliferation rate was determined using a 5-ethynyl-2’- deoxyuridine incorporation assay. The cell cycle distribution was assessed by flow cytometry using propidium iodide staining, and Western blotting was used to assess the expression of BAX, BCL-2, and caspase-3 and to identify any downregulation in the activation of transcription 3 (STAT3), protein kinase B (Akt), and extracellular signal-regulated kinase (ERK1/2). Results • The plumbagin concentrations of 5–20 mmol/L reduced the viability of the GC cells in a dependent manner. Plumbagin suppressed the expression of BAX, BCL-2, pro-caspase-3, and cleaved-caspase-3. It also restrained the expression and phosphorylation of STAT3 and decreased the phosphorylation of Akt1 but did not change the total protein or phosphorylation levels of ERK1/2. Conclusions • Plumbagin inhibits cell apoptosis in human GC cells, and that effect may be related with its ability to suppress phosphorylation of STAT3 and Akt. Given those 2 effects, plumbagin may be a promising agent in the treatment of gastric cancer.
- Subjects
GASTROINTESTINAL cancer; CANCER chemotherapy; RADIOTHERAPY; PATIENT acceptance of health care; HEALTH outcome assessment; PHOSPHORYLATION; PROTEINS; DIAGNOSIS
- Publication
Alternative Therapies in Health & Medicine, 2017, Vol 23, Issue 7, p42
- ISSN
1078-6791
- Publication type
Article