Analysis of the Effects of SAHA on Cancer Stem Cell Markers in Non-Small Cell Lung Cancer Cells
Abstract
In the United States, lung cancer is the third most common form of cancer and shows the highest mortality rate. The most prevalent form is Non-Small Cell Lung Cancer (NSCLC), accounting for 84% of cases. Similar to other solid tumors, several putative surface markers for lung cancer stem cells have been identified, including CD44 and CD133. Cancer stem cells (CSC), with their self-renewal ability and multilineage differentiation potential, are a critical subpopulation of tumor cells that can drive cancer initiation, growth, and resistance to therapy. Reports showed that Hedgehog (HH), Notch, JAK/STAT, PI3K/Akt/mTOR, and Wnt/β-catenin pathways are regulating the transformation of CSCs. In the present study, we analyzed the effect of HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) on CSC markers such as CD44, CD133, and ALDH1A1 in H460 and HCC827 cells. The cells were treated with HDAC inhibitor SAHA (7.5 μM), p21 inhibitor UC2288 (5 μM), and their combinations, for 24 h. In H460, SAHA treatment alone downregulated the CD44 protein expression but slightly up-regulated its expression in the UC2288 and SAHA combination treated cells compared to the control. On the other hand, in HCC827 cells, CD133 expression was down-regulated significantly in the SAHA and combination treatments. Our results showed that HDAC inhibitor SAHA could reduce the stemness-related markers in the NSCLC cells. Understanding the stemness-related features will not only provide new knowledge related to cancer pathogenesis, but also will shed new light on possible therapeutic approaches that can target CSCs (This project was supported by The Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida).
Faculty Sponsors
Dr. Thiagaranjan Venkatesan, Dr. Umamaheswari Natarajan, Dr. Mir Saleem, Dr. Appu Rathinavelu
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-6-2021 12:00 PM
End Date
4-9-2021 12:00 PM
Analysis of the Effects of SAHA on Cancer Stem Cell Markers in Non-Small Cell Lung Cancer Cells
Alvin Sherman Library
In the United States, lung cancer is the third most common form of cancer and shows the highest mortality rate. The most prevalent form is Non-Small Cell Lung Cancer (NSCLC), accounting for 84% of cases. Similar to other solid tumors, several putative surface markers for lung cancer stem cells have been identified, including CD44 and CD133. Cancer stem cells (CSC), with their self-renewal ability and multilineage differentiation potential, are a critical subpopulation of tumor cells that can drive cancer initiation, growth, and resistance to therapy. Reports showed that Hedgehog (HH), Notch, JAK/STAT, PI3K/Akt/mTOR, and Wnt/β-catenin pathways are regulating the transformation of CSCs. In the present study, we analyzed the effect of HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) on CSC markers such as CD44, CD133, and ALDH1A1 in H460 and HCC827 cells. The cells were treated with HDAC inhibitor SAHA (7.5 μM), p21 inhibitor UC2288 (5 μM), and their combinations, for 24 h. In H460, SAHA treatment alone downregulated the CD44 protein expression but slightly up-regulated its expression in the UC2288 and SAHA combination treated cells compared to the control. On the other hand, in HCC827 cells, CD133 expression was down-regulated significantly in the SAHA and combination treatments. Our results showed that HDAC inhibitor SAHA could reduce the stemness-related markers in the NSCLC cells. Understanding the stemness-related features will not only provide new knowledge related to cancer pathogenesis, but also will shed new light on possible therapeutic approaches that can target CSCs (This project was supported by The Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida).
