Presentation Title

The Emerging Role of GSK-3 Inhibitors as Promising Drug Candidates in NSCLC

Speaker Credentials

Ph.D.

College

College of Pharmacy

Location

Nova Southeastern University, Davie, Florida, USA

Format

Podium Presentation

Start Date

21-2-2020 8:30 AM

End Date

21-2-2020 4:00 PM

Abstract

Objective. This study was conducted to assess the apoptotic role of GSK-3 inhibitors: BIO and CHIR 98014 against H460 K-Ras mutant (mut) and H1975 K-Ras wild type (wt) Non-small cell lung cancer (NSCLC) cells. Background. NSCLC accounts for 80% - 85% of lung cancers, with mutation of KRAS being the most frequent aberration. Our study was designed to determine the use of GSK-3 inhibitors as apoptotic inducers against NSCLC cells. Methods. In our study, the cell viability and cell proliferation of H460 and H1975 were measured using MTT and BrdU assay after 24, 48, and 72 h of BIO and CHIR 98014 treatments. Imaging studies to assess Reactive oxygen species (ROS), Mitochondrial Membrane Potential (MMP), and Caspase-3/7 cleavage were conducted. The trans-endothelial migratory assay was conducted to assess the potential of BIO and CHIR 98014 for inhibiting cancer metastasis. Western blot analysis was conducted for measuring pGSK-3, phospho-p53, p21, XIAP, BAX, LC3B, Caspase-3, and Caspase-9 levels. Results. GSK-3 inhibitors significantly reduced the cell viability after 24 h treatment in H1975 compared to H460 cells. In addition, BIO and CHIR 98014 demonstrated significant upregulation of ROS levels, while decreasing its mitochondrial membrane potential, leading to cleavage of Caspase-3, 7, and 9. Interestingly, a significant elevation of phospho-p53, p21, and LC3B levels was observed with BIO and CHIR 98014 treatments. Conclusion. Our results indicated that GSK-3 inhibitors were able to induce cell death by activating both extrinsic and intrinsic apoptotic pathways. Grants. This study was funded by the PFRDG grant 334818 and the financial support from the Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida.

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Feb 21st, 8:30 AM Feb 21st, 4:00 PM

The Emerging Role of GSK-3 Inhibitors as Promising Drug Candidates in NSCLC

Nova Southeastern University, Davie, Florida, USA

Objective. This study was conducted to assess the apoptotic role of GSK-3 inhibitors: BIO and CHIR 98014 against H460 K-Ras mutant (mut) and H1975 K-Ras wild type (wt) Non-small cell lung cancer (NSCLC) cells. Background. NSCLC accounts for 80% - 85% of lung cancers, with mutation of KRAS being the most frequent aberration. Our study was designed to determine the use of GSK-3 inhibitors as apoptotic inducers against NSCLC cells. Methods. In our study, the cell viability and cell proliferation of H460 and H1975 were measured using MTT and BrdU assay after 24, 48, and 72 h of BIO and CHIR 98014 treatments. Imaging studies to assess Reactive oxygen species (ROS), Mitochondrial Membrane Potential (MMP), and Caspase-3/7 cleavage were conducted. The trans-endothelial migratory assay was conducted to assess the potential of BIO and CHIR 98014 for inhibiting cancer metastasis. Western blot analysis was conducted for measuring pGSK-3, phospho-p53, p21, XIAP, BAX, LC3B, Caspase-3, and Caspase-9 levels. Results. GSK-3 inhibitors significantly reduced the cell viability after 24 h treatment in H1975 compared to H460 cells. In addition, BIO and CHIR 98014 demonstrated significant upregulation of ROS levels, while decreasing its mitochondrial membrane potential, leading to cleavage of Caspase-3, 7, and 9. Interestingly, a significant elevation of phospho-p53, p21, and LC3B levels was observed with BIO and CHIR 98014 treatments. Conclusion. Our results indicated that GSK-3 inhibitors were able to induce cell death by activating both extrinsic and intrinsic apoptotic pathways. Grants. This study was funded by the PFRDG grant 334818 and the financial support from the Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida.