Presentation Title

The Impact of MDM2 inhibition on the Expression Levels of XIAP on Various Cancer Cell lines

Speaker Credentials

BS

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

The Impact of MDM2 inhibition on the Expression Levels of XIAP on Various Cancer Cell lines Christopher Garcia, Halmos College of Natural Sciences and Oceanography, Thiagarajan Venkatensan, Ph.D., Kyle Boltson, OMS-III, College of Osteopathic Medicine, Ahmed Atif, OMS-II, College of Osteopathic Medicine, Mike Barry, OMS-II, College of Osteopathic Medicine, and Appu Rathinavelu, Ph.D. Background. Overexpression of the oncogenic Murine Double Minute 2 homolog (MDM2) gene is enhanced during cancer development and continues through disease progression. X-linked Inhibitor of Apoptosis Protein (XIAP) binds to MDM2 protein and stabilizes its pro-cancerous function. XIAP-MDM2 heterodimerization occurs when XIAP binds to the Really Interesting New Gene (RING) domain of the MDM2 protein. Also, XIAP inhibits the pro-apoptotic proteins caspase 3, 7 and 9; which are the regulators of the intrinsic pathway of the cellular apoptosis. Objective. The goal of our study was to determine whether inhibition of MDM2 using RG7388 (MDM2 specific inhibitor) will decrease the level of XIAP in MDM2 overexpressing cancer cells. Methods. For this purpose, we analyzed the expression levels of XIAP and cell survival in LNCaP (Prostate cancer), LNCaP-MST (MDM2 transfected cells), SJSA-1 (Osteosarcoma) and GI-101A (breast cancer) cells via western blotting, MTT assay, and the trypan blue exclusion test. Notably, the XIAP expression is significantly higher in the LNCaP-MST and SJSA-1 cells, which also have elevated expression of MDM2. Results. Our results show a positive correlation between MDM2 and XIAP expressions in cancer cells. Conclusion. Treatment with RG7388 decreased XIAP expression, and inversely correlated with the upregulated levels of caspase enzymes, and activation of the intrinsic apoptosis pathway. However, further studies are warranted to confirm the intracellular mechanisms involved in the regulation of XIAP in MDM2 positive cancers. Grants. This project was supported by 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 Impact of MDM2 inhibition on the Expression Levels of XIAP on Various Cancer Cell lines

Nova Southeastern University, Davie, Florida, USA

The Impact of MDM2 inhibition on the Expression Levels of XIAP on Various Cancer Cell lines Christopher Garcia, Halmos College of Natural Sciences and Oceanography, Thiagarajan Venkatensan, Ph.D., Kyle Boltson, OMS-III, College of Osteopathic Medicine, Ahmed Atif, OMS-II, College of Osteopathic Medicine, Mike Barry, OMS-II, College of Osteopathic Medicine, and Appu Rathinavelu, Ph.D. Background. Overexpression of the oncogenic Murine Double Minute 2 homolog (MDM2) gene is enhanced during cancer development and continues through disease progression. X-linked Inhibitor of Apoptosis Protein (XIAP) binds to MDM2 protein and stabilizes its pro-cancerous function. XIAP-MDM2 heterodimerization occurs when XIAP binds to the Really Interesting New Gene (RING) domain of the MDM2 protein. Also, XIAP inhibits the pro-apoptotic proteins caspase 3, 7 and 9; which are the regulators of the intrinsic pathway of the cellular apoptosis. Objective. The goal of our study was to determine whether inhibition of MDM2 using RG7388 (MDM2 specific inhibitor) will decrease the level of XIAP in MDM2 overexpressing cancer cells. Methods. For this purpose, we analyzed the expression levels of XIAP and cell survival in LNCaP (Prostate cancer), LNCaP-MST (MDM2 transfected cells), SJSA-1 (Osteosarcoma) and GI-101A (breast cancer) cells via western blotting, MTT assay, and the trypan blue exclusion test. Notably, the XIAP expression is significantly higher in the LNCaP-MST and SJSA-1 cells, which also have elevated expression of MDM2. Results. Our results show a positive correlation between MDM2 and XIAP expressions in cancer cells. Conclusion. Treatment with RG7388 decreased XIAP expression, and inversely correlated with the upregulated levels of caspase enzymes, and activation of the intrinsic apoptosis pathway. However, further studies are warranted to confirm the intracellular mechanisms involved in the regulation of XIAP in MDM2 positive cancers. Grants. This project was supported by The Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida.