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α-Mangostin suppresses human gastric adenocarcinoma cells in vitro via blockade of Stat3 signaling pathway.

Shan T, Cui XJ, Li W, Lin WR, Lu HW, Li YM, Chen X, Wu T - Acta Pharmacol. Sin. (2014)

Bottom Line: Treatment with α-mangostin (3-10 μg/mL) inhibited the viability of both BGC-823 and SGC-7901 cells in dose- and time-manners.Furthermore, α-mangostin (7 μg/mL) time-dependently increased the apoptosis index of the cancer cells, reduced the mitochondrial membrane potential of the cancer cells, and significantly increased the release of cytochrome c and AIF into cytoplasm.Moreover, the α-mangostin treatment markedly suppressed the constitutive Stat3 protein activation, and Stat3-regulated Bcl-xL and Mcl-1 protein levels in the cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710004, China.

ABSTRACT

Aim: To investigate the anti-tumor effects of α-mangostin, a major xanthone identified in the pericarp of mangosteen (Garcinia mangostana Linn), against human gastric adenocarcinoma cells in vitro, and the mechanisms of the effects.

Methods: Human gastric adenocarcinoma cell lines BGC-823 and SGC-7901 were treated with α-mangostin. The cell viability was measured with MTT assay, and cell apoptosis was examined using flow cytometry and TUNEL assay. The expression of the relevant proteins was detected using Western blot.

Results: Treatment with α-mangostin (3-10 μg/mL) inhibited the viability of both BGC-823 and SGC-7901 cells in dose- and time-manners. Furthermore, α-mangostin (7 μg/mL) time-dependently increased the apoptosis index of the cancer cells, reduced the mitochondrial membrane potential of the cancer cells, and significantly increased the release of cytochrome c and AIF into cytoplasm. Moreover, the α-mangostin treatment markedly suppressed the constitutive Stat3 protein activation, and Stat3-regulated Bcl-xL and Mcl-1 protein levels in the cancer cells.

Conclusion: The anti-tumor effects of α-mangostin against human gastric adenocarcinoma cells in vitro can be partly attributed to blockade of Stat3 signaling pathway.

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Related in: MedlinePlus

Mitochondrial dysfunction in α-mangostin-treated cells. Electron microscopic observations indicated mitochondrial swelling 3 h after incubation with α-mangostin in BGC-823 (A) and SGC-7901 (B) cells. The release of cytochrome c (Cyt.c) and AIF into cytoplasm was detected at 3 h by Western blotting in BGC-823 (C) and SGC-7901 (D) cells, respectively. (G, H) quantification of Western blotting data. Decreases in ΔΨm were also observed 3 h after the treatment with α-mangostin by flow cytometry in BGC-823 (E) and SGC-7901 (F) cells. Data from at least three independent experiments with duplicate determinations are expressed as the mean±SEM. bP<0.05 vs control.
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fig3: Mitochondrial dysfunction in α-mangostin-treated cells. Electron microscopic observations indicated mitochondrial swelling 3 h after incubation with α-mangostin in BGC-823 (A) and SGC-7901 (B) cells. The release of cytochrome c (Cyt.c) and AIF into cytoplasm was detected at 3 h by Western blotting in BGC-823 (C) and SGC-7901 (D) cells, respectively. (G, H) quantification of Western blotting data. Decreases in ΔΨm were also observed 3 h after the treatment with α-mangostin by flow cytometry in BGC-823 (E) and SGC-7901 (F) cells. Data from at least three independent experiments with duplicate determinations are expressed as the mean±SEM. bP<0.05 vs control.

Mentions: Mitochondrial function reportedly precedes apoptosis protein activation25,26. To understand whether α-mangostin induces gastric adenocarcinoma cell apoptosis via a mitochondrial pathway, we investigated various parameters of mitochondrial dysfunction 3 h after treatment with α-mangostin (7 μg/mL). Electron microscopic observations indicated mitochondrial swelling 3 h after incubation with α-mangostin (Figure 3A, 3B). The release of cytochrome c (Cyt.c) and AIF into the cytoplasm was detected after 3 h (Figure 3C, 3D, 3G, 3H; P<0.05). Decreases in ΔΨm (Figures 3E, 3F) were also observed 3 h after treatment with α-mangostin using a flow cytometry assay (P<0.05). These results indicated that mitochondrial dysfunction is induced by α-mangostin and is involved in gastric adenocarcinoma cell apoptosis.


α-Mangostin suppresses human gastric adenocarcinoma cells in vitro via blockade of Stat3 signaling pathway.

Shan T, Cui XJ, Li W, Lin WR, Lu HW, Li YM, Chen X, Wu T - Acta Pharmacol. Sin. (2014)

Mitochondrial dysfunction in α-mangostin-treated cells. Electron microscopic observations indicated mitochondrial swelling 3 h after incubation with α-mangostin in BGC-823 (A) and SGC-7901 (B) cells. The release of cytochrome c (Cyt.c) and AIF into cytoplasm was detected at 3 h by Western blotting in BGC-823 (C) and SGC-7901 (D) cells, respectively. (G, H) quantification of Western blotting data. Decreases in ΔΨm were also observed 3 h after the treatment with α-mangostin by flow cytometry in BGC-823 (E) and SGC-7901 (F) cells. Data from at least three independent experiments with duplicate determinations are expressed as the mean±SEM. bP<0.05 vs control.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4125713&req=5

fig3: Mitochondrial dysfunction in α-mangostin-treated cells. Electron microscopic observations indicated mitochondrial swelling 3 h after incubation with α-mangostin in BGC-823 (A) and SGC-7901 (B) cells. The release of cytochrome c (Cyt.c) and AIF into cytoplasm was detected at 3 h by Western blotting in BGC-823 (C) and SGC-7901 (D) cells, respectively. (G, H) quantification of Western blotting data. Decreases in ΔΨm were also observed 3 h after the treatment with α-mangostin by flow cytometry in BGC-823 (E) and SGC-7901 (F) cells. Data from at least three independent experiments with duplicate determinations are expressed as the mean±SEM. bP<0.05 vs control.
Mentions: Mitochondrial function reportedly precedes apoptosis protein activation25,26. To understand whether α-mangostin induces gastric adenocarcinoma cell apoptosis via a mitochondrial pathway, we investigated various parameters of mitochondrial dysfunction 3 h after treatment with α-mangostin (7 μg/mL). Electron microscopic observations indicated mitochondrial swelling 3 h after incubation with α-mangostin (Figure 3A, 3B). The release of cytochrome c (Cyt.c) and AIF into the cytoplasm was detected after 3 h (Figure 3C, 3D, 3G, 3H; P<0.05). Decreases in ΔΨm (Figures 3E, 3F) were also observed 3 h after treatment with α-mangostin using a flow cytometry assay (P<0.05). These results indicated that mitochondrial dysfunction is induced by α-mangostin and is involved in gastric adenocarcinoma cell apoptosis.

Bottom Line: Treatment with α-mangostin (3-10 μg/mL) inhibited the viability of both BGC-823 and SGC-7901 cells in dose- and time-manners.Furthermore, α-mangostin (7 μg/mL) time-dependently increased the apoptosis index of the cancer cells, reduced the mitochondrial membrane potential of the cancer cells, and significantly increased the release of cytochrome c and AIF into cytoplasm.Moreover, the α-mangostin treatment markedly suppressed the constitutive Stat3 protein activation, and Stat3-regulated Bcl-xL and Mcl-1 protein levels in the cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710004, China.

ABSTRACT

Aim: To investigate the anti-tumor effects of α-mangostin, a major xanthone identified in the pericarp of mangosteen (Garcinia mangostana Linn), against human gastric adenocarcinoma cells in vitro, and the mechanisms of the effects.

Methods: Human gastric adenocarcinoma cell lines BGC-823 and SGC-7901 were treated with α-mangostin. The cell viability was measured with MTT assay, and cell apoptosis was examined using flow cytometry and TUNEL assay. The expression of the relevant proteins was detected using Western blot.

Results: Treatment with α-mangostin (3-10 μg/mL) inhibited the viability of both BGC-823 and SGC-7901 cells in dose- and time-manners. Furthermore, α-mangostin (7 μg/mL) time-dependently increased the apoptosis index of the cancer cells, reduced the mitochondrial membrane potential of the cancer cells, and significantly increased the release of cytochrome c and AIF into cytoplasm. Moreover, the α-mangostin treatment markedly suppressed the constitutive Stat3 protein activation, and Stat3-regulated Bcl-xL and Mcl-1 protein levels in the cancer cells.

Conclusion: The anti-tumor effects of α-mangostin against human gastric adenocarcinoma cells in vitro can be partly attributed to blockade of Stat3 signaling pathway.

Show MeSH
Related in: MedlinePlus