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| Status |
Public on Sep 10, 2023 |
| Title |
The SGLT2 inhibitor canagliflozin suppresses growth and enhances prostate cancer response to radiotherapy |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Radiotherapy (RT) is a non-invasive standard treatment for prostate cancer (PC). However, PC develops radio-resistance, highlighting a need for agents to improve RT response. Canagliflozin, an inhibitor of sodium-glucose co-transporter-2, is approved for use in diabetes and heart failure, but is also shown to inhibit PC growth. However, whether canagliflozin can improve RT response in PC remains unknown. Here, we show that well-tolerated doses of canagliflozin suppress proliferation and survival of androgen-sensitive and insensitive human PC cells and tumors and sensitize them to RT. Canagliflozin blocks mitochondrial respiration, promotes AMPK activity, inhibits the MAPK and mTOR-p70S6k/4EBP1 pathways, activates cell cycle checkpoints, and inhibits proliferation in part through HIF-1š¼ suppression. Canagliflozin mediates transcriptional reprogramming of several metabolic and survival pathways known to be regulated by ETS and E2F family transcription factors. Genes downregulated by canagliflozin are associated with poor PC prognosis. This study lays the groundwork for clinical investigation of canagliflozin in PC prevention and treatment in combination with RT.
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| Overall design |
In this study, RNAseq was designed to examined canagliflozinās anti-tumor mechanism of action alone and in combination with radiotherapy in CRPC and mCRPC models of prostate cancer.
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| Web link |
https://www.nature.com/articles/s42003-023-05289-w
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| Contributor(s) |
Ali A, Mekhaeil B, Biziotis O, Tsakiridis EE, Ahmadi E, Wu J, Wang S, Singh K, Menjolian G, Farrell T, Mesci A, Liu S, Berg T, Bramson JL, Steinberg GR, Tsakiridis T |
| Citation(s) |
37684337 |
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| Submission date |
Jul 31, 2023 |
| Last update date |
Sep 10, 2023 |
| Contact name |
Amr Mohamed Ahmed Ali |
| E-mail(s) |
amr30903@gmail.com
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| Phone |
7055077573
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| Organization name |
Mcmaster University
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| Department |
Oncology
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| Lab |
Dr. Tsakiridis
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| Street address |
699 concession street-4-212
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| City |
Hamilton |
| State/province |
ON |
| ZIP/Postal code |
L8V2C5 |
| Country |
Canada |
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| Platforms (1) |
| GPL18460 |
Illumina HiSeq 1500 (Homo sapiens) |
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| Samples (18)
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| GSM7670010 |
PC3 cells treated with DMSO (Control A) 24Hr |
| GSM7670011 |
PC3 cells treated with DMSO (Control B) 24Hr |
| GSM7670012 |
PC3 cells treated with DMSO (Control C) 24Hr |
| GSM7670013 |
PC3 cells treated with Canagliflozin (10uM) (10CANA A) 24Hr |
| GSM7670014 |
PC3 cells treated with Canagliflozin (10uM) (10CANA B) 24Hr |
| GSM7670015 |
PC3 cells treated with Canagliflozin (10uM) (10CANA C) 24Hr |
| GSM7670016 |
22RV1 cells treated with DMSO (Control A) 24Hr |
| GSM7670017 |
22RV1 cells treated with DMSO (Control B) 24Hr |
| GSM7670018 |
22RV1 cells treated with DMSO (Control C) 24Hr |
| GSM7670019 |
22RV1 cells treated with Canagliflozin (10uM) (10CANA A) 24Hr |
| GSM7670020 |
22RV1 cells treated with Canagliflozin (10uM) (10CANA B) 24Hr |
| GSM7670021 |
22RV1 cells treated with Canagliflozin (10uM) (10CANA C) 24Hr |
| GSM7670022 |
22RV1 cells treated with Radiation (5GY) (RT(5Gy A) 24Hr |
| GSM7670023 |
22RV1 cells treated with Radiation (5GY) (RT(5Gy B) 24Hr |
| GSM7670024 |
22RV1 cells treated with Radiation (5GY) (RT(5Gy C) 24Hr |
| GSM7670025 |
22RV1 cells treated with Canagliflozin (10uM) + Radiation (5Gy) (RT(5Gy)+10Cana-A) 24Hr |
| GSM7670026 |
22RV1 cells treated with Canagliflozin (10uM) + Radiation (5Gy) (RT(5Gy)+10Cana-B) 24Hr |
| GSM7670027 |
22RV1 cells treated with Canagliflozin (10uM) + Radiation (5Gy) (RT(5Gy)+10Cana-C) 24Hr |
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| Relations |
| BioProject |
PRJNA1000568 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE239688_1-_22RV1_rlog_normalized_feature_count_RNAseq_List_Canagliflozin_10uM_vs_Control_.xlsx |
3.3 Mb |
(ftp)(http) |
XLSX |
| GSE239688_2-_22RV1_rlog_FDR_filter_normalized_feature_count_RNAseq_List_Radiation_5Gy_vs_Control_.xlsx |
1.7 Mb |
(ftp)(http) |
XLSX |
| GSE239688_3-_22RV1_rlog_normalized_feature_count_RNAseq_List_Combination_canagliflozin_10um+radiation_5gy_vs_Control_.xlsx |
4.3 Mb |
(ftp)(http) |
XLSX |
| GSE239688_4-_22RV1_rlog_normalized_feature_count_RNAseq_List_Irradiated_22RV1_5Gy_vs_irradiated_22RV1_5Gy_treated_with_canagliflozin_10uM_.xlsx |
4.4 Mb |
(ftp)(http) |
XLSX |
| GSE239688_PC3_normalized_feature_count_RNAseq_List_Canagliflozin_10uM_vs_Control_.xlsx |
3.1 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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