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

Zhang L, Tian W, Kim S, Ding W, Tong Y, Chen S - Drug Des Devel Ther (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

ABSTRACT

Background: Arsenic 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.

Methods: The 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.

Results: As4S4 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.

Conclusion: As4S4 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.

No MeSH data available.


Related in: MedlinePlus

Curves of cell viability in gastric cancer cells treated with As4S4.Notes: (A) The cytotoxicity of As4S4 against different cell lines. The comparisons of cytotoxicity of As4S4 against AGS, MGC803, and GES-1 cells when treated for 24 hours. The half-maximal inhibitory concentration values of As4S4 against AGS, MGC803, and GES-1 cells were 2.69, 3.26, and 6.27 μM, respectively. (B) Dose- and time-dependent curves of cell viability in AGS cells treated with As4S4. (C) Dose- and time-dependent curves of cell viability in MGC803 cells treated with As4S4. Data represent the mean ± standard deviation of three independent experiments.
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f1-dddt-9-079: Curves of cell viability in gastric cancer cells treated with As4S4.Notes: (A) The cytotoxicity of As4S4 against different cell lines. The comparisons of cytotoxicity of As4S4 against AGS, MGC803, and GES-1 cells when treated for 24 hours. The half-maximal inhibitory concentration values of As4S4 against AGS, MGC803, and GES-1 cells were 2.69, 3.26, and 6.27 μM, respectively. (B) Dose- and time-dependent curves of cell viability in AGS cells treated with As4S4. (C) Dose- and time-dependent curves of cell viability in MGC803 cells treated with As4S4. Data represent the mean ± standard deviation of three independent experiments.

Mentions: AGS, MGC803, and GES-1 cells were treated with different concentrations of As4S4 (0.00, 0.31, 0.62, 1.25, 2.50, 5.00, 10.00 μM) for 24 hours. The half-maximal inhibitory concentration values (24 hours) of As4S4 for AGS, MGC803, and GES-1 cells were 2.69, 3.26, and 6.27 μM, respectively (Figure 1A), indicating that the wild-type p53-containing AGS cells were more sensitive to As4S4 than the mutant p53-containing MGC803 cells. Furthermore, these gastric cancer cells were more sensitive to As4S4 than the human gastric epithelium cells. Then, gastric cancer cells were treated with different concentrations of As4S4 (0.00, 0.31, 0.62, 1.25, 2.50, 5.00, 10.00 μM) for 24, 48, or 72 hours, respectively. Results showed that As4S4 inhibited the proliferation of gastric cancer cells in a time- and dose-dependent manner between 0.31 μM and 10.00 μM concentrations (Figure 1B and C).


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

Zhang L, Tian W, Kim S, Ding W, Tong Y, Chen S - Drug Des Devel Ther (2014)

Curves of cell viability in gastric cancer cells treated with As4S4.Notes: (A) The cytotoxicity of As4S4 against different cell lines. The comparisons of cytotoxicity of As4S4 against AGS, MGC803, and GES-1 cells when treated for 24 hours. The half-maximal inhibitory concentration values of As4S4 against AGS, MGC803, and GES-1 cells were 2.69, 3.26, and 6.27 μM, respectively. (B) Dose- and time-dependent curves of cell viability in AGS cells treated with As4S4. (C) Dose- and time-dependent curves of cell viability in MGC803 cells treated with As4S4. Data represent the mean ± standard deviation of three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4274045&req=5

f1-dddt-9-079: Curves of cell viability in gastric cancer cells treated with As4S4.Notes: (A) The cytotoxicity of As4S4 against different cell lines. The comparisons of cytotoxicity of As4S4 against AGS, MGC803, and GES-1 cells when treated for 24 hours. The half-maximal inhibitory concentration values of As4S4 against AGS, MGC803, and GES-1 cells were 2.69, 3.26, and 6.27 μM, respectively. (B) Dose- and time-dependent curves of cell viability in AGS cells treated with As4S4. (C) Dose- and time-dependent curves of cell viability in MGC803 cells treated with As4S4. Data represent the mean ± standard deviation of three independent experiments.
Mentions: AGS, MGC803, and GES-1 cells were treated with different concentrations of As4S4 (0.00, 0.31, 0.62, 1.25, 2.50, 5.00, 10.00 μM) for 24 hours. The half-maximal inhibitory concentration values (24 hours) of As4S4 for AGS, MGC803, and GES-1 cells were 2.69, 3.26, and 6.27 μM, respectively (Figure 1A), indicating that the wild-type p53-containing AGS cells were more sensitive to As4S4 than the mutant p53-containing MGC803 cells. Furthermore, these gastric cancer cells were more sensitive to As4S4 than the human gastric epithelium cells. Then, gastric cancer cells were treated with different concentrations of As4S4 (0.00, 0.31, 0.62, 1.25, 2.50, 5.00, 10.00 μM) for 24, 48, or 72 hours, respectively. Results showed that As4S4 inhibited the proliferation of gastric cancer cells in a time- and dose-dependent manner between 0.31 μM and 10.00 μM concentrations (Figure 1B and C).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

ABSTRACT

Background: Arsenic 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.

Methods: The 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.

Results: As4S4 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.

Conclusion: As4S4 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.

No MeSH data available.


Related in: MedlinePlus