Abstract
Purpose: To investigate the cytotoxic effect of pumilaside A from Litchi semen against human gastric cancer BGC823 cells, and unravel its possible mechanism(s) of action.Methods: The cytotoxic activity of pumilaside A (5 - 40 μg/mL) against BGC823 cells was assessed by thiazolyl blue tetrazolium bromide assay. The pro-apoptotic effect of PA (10, 20 or 40 μg/mL) on BGC823 cells was monitored by flow cytometry, while the mechanisms involved were investigated using western blot.Results: Pumilaside A significantly produced cytotoxic activity against BGC823 cells (IC50 = 25.43 μg/mL) and induced apoptosis in BGC823 cells (p < 0.01). Treatment with pumilaside A led to significant upregulation of pro-apoptotic factors (Fas, FasL, FADD, Bax, Apaf-1, and c-caspase -8, 9 and 10), and downregulation of anti-apoptotic factors (survivin and Bcl-2, p < 0.05, 0.01). In addition, pumilaside A increased the cytoplasmic levels of Smac and cytochrome c in BGC823 cells by enhancing their mitochondrial release, and significantly upregulated the levels of executioner c-caspases-3, 6 and 7 (p < 0.05, 0.01).Conclusion: Pumilaside A shows good cytotoxic activity against BGC823 cells via a mechanism related to activation of death receptor- and mitochondria-mediated apoptotic pathways. Thus, pumilaside A has a potential for use as an anti-gastric cancer agent.Keywords: Litchi semen, Pumilaside A, BGC823 cells, Cytotoxicity, Apoptosis
Highlights
At present, gastric cancer is the second leading cause of cancer death, and ranks fourth in global cancer prevalence [1,2]
The results showed that Pumilaside A (PA) (10, 20 or 40 μg/mL) induced significant apoptosis in BGC823 cells, relative to the control (p < 0.01; Figure 3)
These results revealed that the cytotoxicity of PA was due to apoptosis
Summary
Gastric cancer is the second leading cause of cancer death, and ranks fourth in global cancer prevalence [1,2]. Interventional therapy, radiotherapy, chemotherapy and biotherapy constitute the main treatment strategies for gastric carcinoma [3,4,5,6]. It has been suggested that chemotherapy is a vital aspect of this treatment [7]. Prolonged use of chemotherapy drugs by gastric cancer patients is necessary to enhance therapeutic outcomes. Prolonged use of these drugs is associated with development of drug resistance by the cancer cells, leading to reduced effectiveness of chemotherapy [8]. It is crucial to evolve newer and more effective chemotherapy drugs for treating gastric cancer
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