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Glucosamine suppresses proliferation of human prostate carcinoma DU145 cells through inhibition of STAT3 signaling.

Chesnokov V, Sun C, Itakura K - Cancer Cell Int. (2009)

Bottom Line: The effects of glucosamine were associated with up-regulation of p21waf1/cip, a CDK inhibitor.Glucosamine inhibited phosphorylation of STAT3 at the Tyr705 residue and as a result, reduced STAT3 DNA binding and transcriptional activities.Contrary to DU145 cells, glucosamine did not affect proliferation of other human prostate cancer PC-3 and C4-2B cells, in which STAT 3 signal pathway is not constitutively active.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Biology, Beckman Research Institute of the City of Hope, 1450 East Duarte road, Duarte, California 91010, USA. vchesnokov@coh.org

ABSTRACT

Background: Glucosamine is known as a toxic agent for several malignant cell lines and transplanted tumors with little toxicity to normal host tissues. However, the mechanisms underlying anticancer activity of glucosamine are poorly understood. To study the mechanisms, the human prostate cancer DU145 cells were used for the model.

Results: Glucosamine at concentration 2 mM suppressed proliferation and induced death of DU145 cells. Detailed analysis showed that glucosamine decreased DNA synthesis, arrested cell cycle at G1 phase and induced apoptosis. The effects of glucosamine were associated with up-regulation of p21waf1/cip, a CDK inhibitor. Our further studies identified glucosamine as an inhibitor of signal transducer and activator of transcription (STAT) 3 which is constitutively activated in many cancer cells including DU145 cells. Glucosamine inhibited phosphorylation of STAT3 at the Tyr705 residue and as a result, reduced STAT3 DNA binding and transcriptional activities. Indeed, the expression of apoptosis inhibitor survivin, which is well known target of STAT3, was suppressed. Contrary to DU145 cells, glucosamine did not affect proliferation of other human prostate cancer PC-3 and C4-2B cells, in which STAT 3 signal pathway is not constitutively active.

Conclusion: Our data identifies glucosamine as a suppressor of STAT3 signaling and suggests that anticancer activity of glucosamine may be attributed to the suppression of STAT3 activity. Potential application of glucosamine for the treatment of tumors with constitutively active STAT3 is proposed.

No MeSH data available.


Related in: MedlinePlus

Glucosamine-induced inhibition of growth of DU145 cells. A, DU145 cells were cultured in the absence or presence of 1, 2, or 4 mM glucosamine for 2 or 3 days in 24-well plates. Total number of cells for each well was counted using a hemocytometer. B, BrdU incorporation into DNA of DU145 cells treated with 1, 2, or 4 mM glucosamine for 6, 14, or 24 h is present as % of control without glucosamine. C, Flow cytometry analysis of distribution of DU145 cells in different phases of cell cycle after treatment with 4 mM glucosamine for 24 h. The results of the representative experiment are presented as mean ± standard deviation of the three independent samples. All experiments were repeated at least three times.
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Figure 1: Glucosamine-induced inhibition of growth of DU145 cells. A, DU145 cells were cultured in the absence or presence of 1, 2, or 4 mM glucosamine for 2 or 3 days in 24-well plates. Total number of cells for each well was counted using a hemocytometer. B, BrdU incorporation into DNA of DU145 cells treated with 1, 2, or 4 mM glucosamine for 6, 14, or 24 h is present as % of control without glucosamine. C, Flow cytometry analysis of distribution of DU145 cells in different phases of cell cycle after treatment with 4 mM glucosamine for 24 h. The results of the representative experiment are presented as mean ± standard deviation of the three independent samples. All experiments were repeated at least three times.

Mentions: To examine anti-tumor effects of glucosamine on human prostate cancer cells, the hormone refractory human prostate carcinoma DU145 cells were plated and treated with glucosamine at concentrations 1, 2, and 4 mM for 2 and 3 days. The cells attached to culture flasks were collected and cell numbers were counted using hemocytometer. As shown in Fig. 1A, glucosamine inhibited the proliferation of DU145 cells in a dose-dependent manner. With 1 mM glucosamine, the cell numbers were reduced to 50 and 70% of those of the untreated controls for 2 and 3 days, respectively, and with 2 and 4 mM glucosamine cell proliferation were completely suppressed for 2 and 3 days (Fig. 1A). Since effects of glucosamine on cell proliferation was evident at 2 mM, all subsequent experiments were performed using this concentration unless specified otherwise.


Glucosamine suppresses proliferation of human prostate carcinoma DU145 cells through inhibition of STAT3 signaling.

Chesnokov V, Sun C, Itakura K - Cancer Cell Int. (2009)

Glucosamine-induced inhibition of growth of DU145 cells. A, DU145 cells were cultured in the absence or presence of 1, 2, or 4 mM glucosamine for 2 or 3 days in 24-well plates. Total number of cells for each well was counted using a hemocytometer. B, BrdU incorporation into DNA of DU145 cells treated with 1, 2, or 4 mM glucosamine for 6, 14, or 24 h is present as % of control without glucosamine. C, Flow cytometry analysis of distribution of DU145 cells in different phases of cell cycle after treatment with 4 mM glucosamine for 24 h. The results of the representative experiment are presented as mean ± standard deviation of the three independent samples. All experiments were repeated at least three times.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2747838&req=5

Figure 1: Glucosamine-induced inhibition of growth of DU145 cells. A, DU145 cells were cultured in the absence or presence of 1, 2, or 4 mM glucosamine for 2 or 3 days in 24-well plates. Total number of cells for each well was counted using a hemocytometer. B, BrdU incorporation into DNA of DU145 cells treated with 1, 2, or 4 mM glucosamine for 6, 14, or 24 h is present as % of control without glucosamine. C, Flow cytometry analysis of distribution of DU145 cells in different phases of cell cycle after treatment with 4 mM glucosamine for 24 h. The results of the representative experiment are presented as mean ± standard deviation of the three independent samples. All experiments were repeated at least three times.
Mentions: To examine anti-tumor effects of glucosamine on human prostate cancer cells, the hormone refractory human prostate carcinoma DU145 cells were plated and treated with glucosamine at concentrations 1, 2, and 4 mM for 2 and 3 days. The cells attached to culture flasks were collected and cell numbers were counted using hemocytometer. As shown in Fig. 1A, glucosamine inhibited the proliferation of DU145 cells in a dose-dependent manner. With 1 mM glucosamine, the cell numbers were reduced to 50 and 70% of those of the untreated controls for 2 and 3 days, respectively, and with 2 and 4 mM glucosamine cell proliferation were completely suppressed for 2 and 3 days (Fig. 1A). Since effects of glucosamine on cell proliferation was evident at 2 mM, all subsequent experiments were performed using this concentration unless specified otherwise.

Bottom Line: The effects of glucosamine were associated with up-regulation of p21waf1/cip, a CDK inhibitor.Glucosamine inhibited phosphorylation of STAT3 at the Tyr705 residue and as a result, reduced STAT3 DNA binding and transcriptional activities.Contrary to DU145 cells, glucosamine did not affect proliferation of other human prostate cancer PC-3 and C4-2B cells, in which STAT 3 signal pathway is not constitutively active.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Biology, Beckman Research Institute of the City of Hope, 1450 East Duarte road, Duarte, California 91010, USA. vchesnokov@coh.org

ABSTRACT

Background: Glucosamine is known as a toxic agent for several malignant cell lines and transplanted tumors with little toxicity to normal host tissues. However, the mechanisms underlying anticancer activity of glucosamine are poorly understood. To study the mechanisms, the human prostate cancer DU145 cells were used for the model.

Results: Glucosamine at concentration 2 mM suppressed proliferation and induced death of DU145 cells. Detailed analysis showed that glucosamine decreased DNA synthesis, arrested cell cycle at G1 phase and induced apoptosis. The effects of glucosamine were associated with up-regulation of p21waf1/cip, a CDK inhibitor. Our further studies identified glucosamine as an inhibitor of signal transducer and activator of transcription (STAT) 3 which is constitutively activated in many cancer cells including DU145 cells. Glucosamine inhibited phosphorylation of STAT3 at the Tyr705 residue and as a result, reduced STAT3 DNA binding and transcriptional activities. Indeed, the expression of apoptosis inhibitor survivin, which is well known target of STAT3, was suppressed. Contrary to DU145 cells, glucosamine did not affect proliferation of other human prostate cancer PC-3 and C4-2B cells, in which STAT 3 signal pathway is not constitutively active.

Conclusion: Our data identifies glucosamine as a suppressor of STAT3 signaling and suggests that anticancer activity of glucosamine may be attributed to the suppression of STAT3 activity. Potential application of glucosamine for the treatment of tumors with constitutively active STAT3 is proposed.

No MeSH data available.


Related in: MedlinePlus