Abstract
Purpose: To evaluate the effect of triptolide on the induction of cell apoptosis in human gastric cancer BGC-823 cells. Methods: The cytotoxicity of triptolide was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5- diphenyltetrazolium bromide (MTT) assay. The effect of triptolide on cell proliferation was measured using lactate dehydrogenase (LDH) assay. Cell apoptosis was determined by Annexin V/propidium iodide (PI) double-staining assay. Results: MTT results indicate that triptolide significantly decreased cancer cell numbers in dose- and time-dependent manners in MTT assay. Data from LDH assay showed that triptolide markedly induced cytotoxicity in gastric cancer cells. Triptolide also remarkably induced both early and late apoptotic process in BGC-823 cells. In addition, the compound down-regulated the expression of anti-apoptotic Bcell lymphoma-2 (bcl-2) and up-regulated the expression of pro-apoptotic BCL-2-associated X (bax) in a dose-dependent manner. Furthermore, the pro-apoptotic activity of triptolide was involved in the activation of caspase-3 pathway in BGC-823 cells. Conclusion: Taken together, the findings strongly indicates that the pro-apoptotic activity of triptolide is regulated by caspase 3-dependent cascade pathway, and thus needs to be further developed for cancer therapy. Keywords: Triptolide, Gastric cancer therapy, Apoptosis, Cytotoxicity, Caspase
Highlights
Gastric cancer is ranking the second leading cause of cancer-related deaths worldwide [1]
Our results showed that toxic effects were increased in BGC-823 cells by triptolide treatment (10, 20, and 40 nM) in a dosedependent manner (Figure 2)
Cell apoptosis was measured by Annexin V and propidium iodide (PI) double-staining assays using flow cytometry
Summary
Gastric cancer is ranking the second leading cause of cancer-related deaths worldwide [1]. Due to the high rates of side effects and rapid therapeutic resistance, the efficacy of traditional chemotherapeutic drugs in the cancer treatment has declined [3]. The root of Trypterigium wilfordii Hook L, known as “Thunder of God Vine” is one traditional Chinese medicine that has been reported to have diverse biological activities including anti-arthritis, anti-Alzheimer and anti-cancer effects [6,7,8]. Triptolide is demonstrated to have anti-cancer effects in several cancer types including lung cancer [10], liver cancer [11], pancreatic cancer [12], and colon cancer [13]. Triptolide is able to cause pancreatic cancer cell death through induction of apoptosis via inhibition of HSP70 [12]. A recent study suggests that the induction of cell death by triptolide is modified by autophagy in cardiomyocytes [15]
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