Arsenic sulfide, the main component of realgar, a traditional Chinese medicine, induces apoptosis of gastric cancer cells in vitro and in vivo

Abstract

BackgroundArsenic sulfide (As4S4), the main component of realgar, a traditional Chinese medicine, has shown antitumor efficacy in several tumor types, especially for acute promyelocytic leukemia. In this study, we aimed to explore the efficacy and mechanism of As4S4 in gastric cancer.MethodsThe effect of As4S4 on cell proliferation and apoptosis of gastric cancer cells was investigated by MTT assay, 4′,6-diamidino-2-phenylindole (DAPI) staining, and annexin V–fluorescein isothiocyanate/propidium iodide staining using gastric cancer cell lines AGS (harboring wild-type p53) and MGC803 (harboring mutant p53) in vitro. The expression of apoptosis-related proteins was measured by Western blotting, real-time polymerase chain reaction, and immunohistochemistry analysis. Mouse xenograft models were established by inoculation with MGC803 cells, and the morphology and the proportion of apoptotic cells in tumor tissues were detected by hematoxylin and eosin staining and TdT-mediated dUTP nick end labeling (TUNEL) assay, respectively.ResultsAs4S4 inhibited the proliferation and induced apoptosis of AGS and MGC803 cells in a time- and dose-dependent manner. As4S4 upregulated the expression of Bax and MDM2 while downregulated the expression of Bcl-2. The expression of p53 increased significantly in the AGS cells but did not readily increase in the MGC803 cells, which harbored mutant p53. Pifithrin-α, a p53 inhibitor, blocked the modulation of As4S4 on AGS cells, but not on MGC803 cells. Using xenograft as a model, we showed that As4S4 suppressed tumor growth and induced apoptosis in vivo and that the expression of p53 increased accordingly.ConclusionAs4S4 is a potent cytotoxic agent for gastric cancer cells, as it induced apoptosis both in vitro and in vivo through a p53-dependent pathway. Our data indicate that As4S4 may have therapeutic potential in gastric cancer.

Downregulation of eukaryotic translation initiation factor 3b inhibited proliferation and metastasis of gastric cancer

“…We speculated that this might be related to the difference in the cell backgrounds, as SGC7901 is derived from a P53 mutant gastric cancer cell line 28 , and MGC803 is derived from a P53 wild-type gastric cancer cell line 29 . To verify our speculation, we downregulated eIF3b expression in AGS cells (a gastric cancer cell line with wild-type P53 30 ). The expression of IL-8 was detected, and the results show that the downregulation of eIF3b in AGS cells also increased the expression of IL-8 (data not shown), which was consistent with the results in MGC803 cells.…”

The Immunomodulatory Effects of Nidus Vespae on Human Peripheral Blood Immune CellsIn Vitro

“…The third is inducing the apoptosis of tumor cells. Similar to arsenic sulfide (As4S4), the main component of realgar has been shown to induce apoptosis of gastric cancer cells both in vitro and in vivo through a p53-dependent pathway [13]. The final aspect is inhibiting the tumor angiogenesis.…”

<p>Arsenic sulfide induces miR-4665-3p to inhibit gastric cancer cell invasion and migration</p>

“…All medium was supplemented with 10% fetal bovine serum (Thermo Fisher Scientific). Highly purified arsenic sulfide (As 4 S 4 ) was prepared from mined natural realgar and the preparation of As 4 S 4 solution was performed as previously described 20. The stock solution of As 4 S 4 was 133.36 µM and then was diluted to work solution with complete culture medium.…”