Targeting heat shock response in osteosarcoma cells by combination treatment / Dr. Alyaa R Mahmood Al- Khateeb … [et al.]

Metformin has anticancer effects by inhibiting glucose metabolism. Hyperthermia sensitizes cancer cells. It is known that both metformin,hypo- and hyperthermia deregulate mitochondrial metabolism in cancer. However, the mechanism of the additive effect is not known. The combined effect of metformin...

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Main Authors: Mahmood Al- Khateeb, Alyaa R, Froemming, Gabriele Ruth Anisah, Mohd Ismail, Aletza, Abdul Hamid Hasani, Narimah
Format: Research Reports
Language:English
Published: Research Management Institute (RMI) 2013
Subjects:
Online Access:https://ir.uitm.edu.my/id/eprint/26751/1/LP_ALYAA%20R%20MAHMOOD%20AL-%20KHATEEB%20RMI%2013_5.pdf
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author Mahmood Al- Khateeb, Alyaa R
Froemming, Gabriele Ruth Anisah
Mohd Ismail, Aletza
Abdul Hamid Hasani, Narimah
author_facet Mahmood Al- Khateeb, Alyaa R
Froemming, Gabriele Ruth Anisah
Mohd Ismail, Aletza
Abdul Hamid Hasani, Narimah
author_sort Mahmood Al- Khateeb, Alyaa R
collection UITM
description Metformin has anticancer effects by inhibiting glucose metabolism. Hyperthermia sensitizes cancer cells. It is known that both metformin,hypo- and hyperthermia deregulate mitochondrial metabolism in cancer. However, the mechanism of the additive effect is not known. The combined effect of metformin and hypo- or hyperthermia on osteosarcoma cell line (MG-63 cell) viability, DNA damage, glucose metabolism, regulation of apoptotic genes and proteins were investigated. Osteosarcoma (MG-63) cells were treated with metformin IC50 30M for 48h followed by exposure to 45°C, 39°C, 35°C 27°C for 30 min, 1h and 2h , 37°C was served as control. The combinations of metformin with hypo- and hyperthermia significantly downregulated the expression of AKT1 and GSK3(3 genes, which led to a reduce cells viability and an increase in DNA damage. Metformin induced apoptosis and necrosis. The combined effect caused a downregulation of anti-apoptotic Bcl-2. The intrinsic pathway was not activated. Therefore, this study suggests that the combination of metformin with hyperthermia particularly 45°C, enhances apoptosis via Bax/Bid-dependent pathway.
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spelling uitm.eprints-67512023-07-13T07:17:33Z https://ir.uitm.edu.my/id/eprint/26751/ Targeting heat shock response in osteosarcoma cells by combination treatment / Dr. Alyaa R Mahmood Al- Khateeb … [et al.] Mahmood Al- Khateeb, Alyaa R Froemming, Gabriele Ruth Anisah Mohd Ismail, Aletza Abdul Hamid Hasani, Narimah RC0254 Neoplasms. Tumors. Oncology (including Cancer) Metformin has anticancer effects by inhibiting glucose metabolism. Hyperthermia sensitizes cancer cells. It is known that both metformin,hypo- and hyperthermia deregulate mitochondrial metabolism in cancer. However, the mechanism of the additive effect is not known. The combined effect of metformin and hypo- or hyperthermia on osteosarcoma cell line (MG-63 cell) viability, DNA damage, glucose metabolism, regulation of apoptotic genes and proteins were investigated. Osteosarcoma (MG-63) cells were treated with metformin IC50 30M for 48h followed by exposure to 45°C, 39°C, 35°C 27°C for 30 min, 1h and 2h , 37°C was served as control. The combinations of metformin with hypo- and hyperthermia significantly downregulated the expression of AKT1 and GSK3(3 genes, which led to a reduce cells viability and an increase in DNA damage. Metformin induced apoptosis and necrosis. The combined effect caused a downregulation of anti-apoptotic Bcl-2. The intrinsic pathway was not activated. Therefore, this study suggests that the combination of metformin with hyperthermia particularly 45°C, enhances apoptosis via Bax/Bid-dependent pathway. Research Management Institute (RMI) 2013 Research Reports NonPeerReviewed text en https://ir.uitm.edu.my/id/eprint/26751/1/LP_ALYAA%20R%20MAHMOOD%20AL-%20KHATEEB%20RMI%2013_5.pdf Targeting heat shock response in osteosarcoma cells by combination treatment / Dr. Alyaa R Mahmood Al- Khateeb … [et al.]. (2013) [Research Reports] (Unpublished)
spellingShingle RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Mahmood Al- Khateeb, Alyaa R
Froemming, Gabriele Ruth Anisah
Mohd Ismail, Aletza
Abdul Hamid Hasani, Narimah
Targeting heat shock response in osteosarcoma cells by combination treatment / Dr. Alyaa R Mahmood Al- Khateeb … [et al.]
title Targeting heat shock response in osteosarcoma cells by combination treatment / Dr. Alyaa R Mahmood Al- Khateeb … [et al.]
title_full Targeting heat shock response in osteosarcoma cells by combination treatment / Dr. Alyaa R Mahmood Al- Khateeb … [et al.]
title_fullStr Targeting heat shock response in osteosarcoma cells by combination treatment / Dr. Alyaa R Mahmood Al- Khateeb … [et al.]
title_full_unstemmed Targeting heat shock response in osteosarcoma cells by combination treatment / Dr. Alyaa R Mahmood Al- Khateeb … [et al.]
title_short Targeting heat shock response in osteosarcoma cells by combination treatment / Dr. Alyaa R Mahmood Al- Khateeb … [et al.]
title_sort targeting heat shock response in osteosarcoma cells by combination treatment dr alyaa r mahmood al khateeb et al
topic RC0254 Neoplasms. Tumors. Oncology (including Cancer)
url https://ir.uitm.edu.my/id/eprint/26751/1/LP_ALYAA%20R%20MAHMOOD%20AL-%20KHATEEB%20RMI%2013_5.pdf
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