Inhibition of GSK-3 induces differentiation and impaired glucose metabolism in renal cancer
Glycogen synthase kinase-3 (GSK-3), a constitutively active serine/threonine kinase, is a key regulator of numerous cellular processes ranging from glycogen metabolism to cell cycle regulation and proliferation. Consistent with its involvement in many pathways, it has also been implicated in the pat...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
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American Association for Cancer Research
2014
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| Online Access: | http://hdl.handle.net/20.500.11937/20200 |
| _version_ | 1848750240811712512 |
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| author | Pal, K. Cao, Y. Gaisina, I. Bhattacharya, S. Dutta, S. Wang, E. Gunosewoyo, Hendra Kozikowski, A. Billadeau, D. Mukhopadhyay, D. |
| author_facet | Pal, K. Cao, Y. Gaisina, I. Bhattacharya, S. Dutta, S. Wang, E. Gunosewoyo, Hendra Kozikowski, A. Billadeau, D. Mukhopadhyay, D. |
| author_sort | Pal, K. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Glycogen synthase kinase-3 (GSK-3), a constitutively active serine/threonine kinase, is a key regulator of numerous cellular processes ranging from glycogen metabolism to cell cycle regulation and proliferation. Consistent with its involvement in many pathways, it has also been implicated in the pathogenesis of various human diseases including Type II diabetes, Alzheimer's disease, bipolar disorder, inflammation and cancer. Consequently it is recognized as an attractive target for the development of new drugs. In the present study, we investigated the effect of both pharmacological and genetic inhibition of GSK-3 in two different renal cancer cell lines. We have shown potent anti-proliferative activity of 9-ING-41, a maleimide-based GSK-3 inhibitor. The anti-proliferative activity is most likely caused by G0-G1 and G2-M phase arrest as evident from cell cycle analysis. We have established that inhibition of GSK-3 imparted a differentiated phenotype in renal cancer cells. We have also shown that GSK-3 inhibition induced autophagy, likely as a result of imbalanced energy homeostasis caused by impaired glucose metabolism. Additionally, we have demonstrated the antitumor activity of 9-ING-41 in two different subcutaneous xenograft RCC tumor models. To our knowledge, this is the first report describing autophagy induction due to GSK-3 inhibition in renal cancer cells. |
| first_indexed | 2025-11-14T07:33:42Z |
| format | Journal Article |
| id | curtin-20.500.11937-20200 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:33:42Z |
| publishDate | 2014 |
| publisher | American Association for Cancer Research |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-202002017-09-13T13:49:38Z Inhibition of GSK-3 induces differentiation and impaired glucose metabolism in renal cancer Pal, K. Cao, Y. Gaisina, I. Bhattacharya, S. Dutta, S. Wang, E. Gunosewoyo, Hendra Kozikowski, A. Billadeau, D. Mukhopadhyay, D. Glycogen synthase kinase-3 (GSK-3), a constitutively active serine/threonine kinase, is a key regulator of numerous cellular processes ranging from glycogen metabolism to cell cycle regulation and proliferation. Consistent with its involvement in many pathways, it has also been implicated in the pathogenesis of various human diseases including Type II diabetes, Alzheimer's disease, bipolar disorder, inflammation and cancer. Consequently it is recognized as an attractive target for the development of new drugs. In the present study, we investigated the effect of both pharmacological and genetic inhibition of GSK-3 in two different renal cancer cell lines. We have shown potent anti-proliferative activity of 9-ING-41, a maleimide-based GSK-3 inhibitor. The anti-proliferative activity is most likely caused by G0-G1 and G2-M phase arrest as evident from cell cycle analysis. We have established that inhibition of GSK-3 imparted a differentiated phenotype in renal cancer cells. We have also shown that GSK-3 inhibition induced autophagy, likely as a result of imbalanced energy homeostasis caused by impaired glucose metabolism. Additionally, we have demonstrated the antitumor activity of 9-ING-41 in two different subcutaneous xenograft RCC tumor models. To our knowledge, this is the first report describing autophagy induction due to GSK-3 inhibition in renal cancer cells. 2014 Journal Article http://hdl.handle.net/20.500.11937/20200 10.1158/1535-7163.MCT-13-0681 American Association for Cancer Research fulltext |
| spellingShingle | Pal, K. Cao, Y. Gaisina, I. Bhattacharya, S. Dutta, S. Wang, E. Gunosewoyo, Hendra Kozikowski, A. Billadeau, D. Mukhopadhyay, D. Inhibition of GSK-3 induces differentiation and impaired glucose metabolism in renal cancer |
| title | Inhibition of GSK-3 induces differentiation and impaired glucose metabolism in renal cancer |
| title_full | Inhibition of GSK-3 induces differentiation and impaired glucose metabolism in renal cancer |
| title_fullStr | Inhibition of GSK-3 induces differentiation and impaired glucose metabolism in renal cancer |
| title_full_unstemmed | Inhibition of GSK-3 induces differentiation and impaired glucose metabolism in renal cancer |
| title_short | Inhibition of GSK-3 induces differentiation and impaired glucose metabolism in renal cancer |
| title_sort | inhibition of gsk-3 induces differentiation and impaired glucose metabolism in renal cancer |
| url | http://hdl.handle.net/20.500.11937/20200 |