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Ponicidin induces apoptosis via JAK2 and STAT3 signaling pathways in gastric carcinoma.

Liu YF, Lu YM, Qu GQ, Liu Y, Chen WX, Liao XH, Kong WM - Int J Mol Sci (2015)

Bottom Line: The results revealed that ponicidin could inhibit the growth of MKN28 cells significantly in both a time- and dose-dependent manner.The cell cycle was blocked and ROS generation was increased after the cells were treated with ponicidin.We therefore conclude that ponicidin exhibited significant growth inhibition of gastric carcinoma cell line MKN28 and induced apoptosis of MKN28 cells via the signaling pathway regulated by Janus kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3).

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. wangyang163jed@163.com.

ABSTRACT
Ponicidin has a variety of biological effects such as immunoregulatory and anti-inflammatory functions as well as anti-viral functions especially in the upper respiratory tract infection. This study was aimed to elucidate the antitumor effect of ponicidin in gastric carcinoma MKN28 cells and the possible molecular mechanism involved. Cell viability was measured by the Cell Count Kit-8 (CCK8). Cell apoptosis was assessed by flow cytometry as well as cell cycle and reactive oxygen species (ROS) analysis. Western blot analysis was used to detect the active form of caspase-3 as well as Bax and B-cell lymphoma-2 (Bcl-2) expressions after cells were treated with different concentrations of ponicidin. The results revealed that ponicidin could inhibit the growth of MKN28 cells significantly in both a time- and dose-dependent manner. The cell cycle was blocked and ROS generation was increased after the cells were treated with ponicidin. Bcl-2 expression was down-regulated remarkably while Bax expression and the active form of caspase-3 were increased after apoptosis occurred. We therefore conclude that ponicidin exhibited significant growth inhibition of gastric carcinoma cell line MKN28 and induced apoptosis of MKN28 cells via the signaling pathway regulated by Janus kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3). Ponicidin may serve as a potential therapeutic agent for gastric carcinoma.

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Effects of ponicidin on the expression of key proteins involved in cell apoptosis. (A,C) The expression of apoptosis-related proteins was detected by Western blot; (B) Treatment with ponicidin for 6 h: JAK2 and STAT3 phosphorylation decreased dose-dependently and no effects of ponicidin (50 μg/mL) on JAK2 and STAT3 were observed; and (D) Treatment with ponicidin (25, 50 μg/mL) for 48 h increased the expression of Bax and the active form of caspase-3, while it decreased the expression of VEGF, VEGFR2 and Bcl-2, dose-dependently. * p < 0.05, # p < 0.01.
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ijms-16-01576-f005: Effects of ponicidin on the expression of key proteins involved in cell apoptosis. (A,C) The expression of apoptosis-related proteins was detected by Western blot; (B) Treatment with ponicidin for 6 h: JAK2 and STAT3 phosphorylation decreased dose-dependently and no effects of ponicidin (50 μg/mL) on JAK2 and STAT3 were observed; and (D) Treatment with ponicidin (25, 50 μg/mL) for 48 h increased the expression of Bax and the active form of caspase-3, while it decreased the expression of VEGF, VEGFR2 and Bcl-2, dose-dependently. * p < 0.05, # p < 0.01.

Mentions: To clarify the mechanism of MKN28 cells apoptosis induced by ponicidin, the expression of apoptosis-related proteins and the phosphorylation of kinases were detected by western blot. As shown in Figure 5A, treatment with ponicidin (10, 25 and 50 μmol/L) for 6 h decreased JAK2 phosphorylation and STAT3 phosphorylation in a dose-dependent manner, while MKN28 cells treated with ponicidin had no effect on the protein levels of JAK2 and STAT3. Treatment with ponicidin (25, 50 μmol/L) for 48 h also evidently decreased the protein levels of VEGF, VEGFR2 and Bcl-2 in a dose-dependent manner compared to the control group, but increased levels of Bax protein and the active form of caspase-3 (Figure 5B).


Ponicidin induces apoptosis via JAK2 and STAT3 signaling pathways in gastric carcinoma.

Liu YF, Lu YM, Qu GQ, Liu Y, Chen WX, Liao XH, Kong WM - Int J Mol Sci (2015)

Effects of ponicidin on the expression of key proteins involved in cell apoptosis. (A,C) The expression of apoptosis-related proteins was detected by Western blot; (B) Treatment with ponicidin for 6 h: JAK2 and STAT3 phosphorylation decreased dose-dependently and no effects of ponicidin (50 μg/mL) on JAK2 and STAT3 were observed; and (D) Treatment with ponicidin (25, 50 μg/mL) for 48 h increased the expression of Bax and the active form of caspase-3, while it decreased the expression of VEGF, VEGFR2 and Bcl-2, dose-dependently. * p < 0.05, # p < 0.01.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307321&req=5

ijms-16-01576-f005: Effects of ponicidin on the expression of key proteins involved in cell apoptosis. (A,C) The expression of apoptosis-related proteins was detected by Western blot; (B) Treatment with ponicidin for 6 h: JAK2 and STAT3 phosphorylation decreased dose-dependently and no effects of ponicidin (50 μg/mL) on JAK2 and STAT3 were observed; and (D) Treatment with ponicidin (25, 50 μg/mL) for 48 h increased the expression of Bax and the active form of caspase-3, while it decreased the expression of VEGF, VEGFR2 and Bcl-2, dose-dependently. * p < 0.05, # p < 0.01.
Mentions: To clarify the mechanism of MKN28 cells apoptosis induced by ponicidin, the expression of apoptosis-related proteins and the phosphorylation of kinases were detected by western blot. As shown in Figure 5A, treatment with ponicidin (10, 25 and 50 μmol/L) for 6 h decreased JAK2 phosphorylation and STAT3 phosphorylation in a dose-dependent manner, while MKN28 cells treated with ponicidin had no effect on the protein levels of JAK2 and STAT3. Treatment with ponicidin (25, 50 μmol/L) for 48 h also evidently decreased the protein levels of VEGF, VEGFR2 and Bcl-2 in a dose-dependent manner compared to the control group, but increased levels of Bax protein and the active form of caspase-3 (Figure 5B).

Bottom Line: The results revealed that ponicidin could inhibit the growth of MKN28 cells significantly in both a time- and dose-dependent manner.The cell cycle was blocked and ROS generation was increased after the cells were treated with ponicidin.We therefore conclude that ponicidin exhibited significant growth inhibition of gastric carcinoma cell line MKN28 and induced apoptosis of MKN28 cells via the signaling pathway regulated by Janus kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3).

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. wangyang163jed@163.com.

ABSTRACT
Ponicidin has a variety of biological effects such as immunoregulatory and anti-inflammatory functions as well as anti-viral functions especially in the upper respiratory tract infection. This study was aimed to elucidate the antitumor effect of ponicidin in gastric carcinoma MKN28 cells and the possible molecular mechanism involved. Cell viability was measured by the Cell Count Kit-8 (CCK8). Cell apoptosis was assessed by flow cytometry as well as cell cycle and reactive oxygen species (ROS) analysis. Western blot analysis was used to detect the active form of caspase-3 as well as Bax and B-cell lymphoma-2 (Bcl-2) expressions after cells were treated with different concentrations of ponicidin. The results revealed that ponicidin could inhibit the growth of MKN28 cells significantly in both a time- and dose-dependent manner. The cell cycle was blocked and ROS generation was increased after the cells were treated with ponicidin. Bcl-2 expression was down-regulated remarkably while Bax expression and the active form of caspase-3 were increased after apoptosis occurred. We therefore conclude that ponicidin exhibited significant growth inhibition of gastric carcinoma cell line MKN28 and induced apoptosis of MKN28 cells via the signaling pathway regulated by Janus kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3). Ponicidin may serve as a potential therapeutic agent for gastric carcinoma.

Show MeSH
Related in: MedlinePlus