Death by Inflammation – Effects of Chronic Glucocorticoid Exposure on Pyroptosis in A549 lung cancer cells

Abstract:

Glucocorticoids are steroid hormones both secreted by the body and administered to patients with inflammatory diseases for their anti-inflammatory properties. Chronic usage of these drugs has been associated with immunosuppression and osteoporosis; chronic models of glucocorticoid usage are needed to monitor potential comorbidities and disease outcomes. For example, glucocorticoids have demonstrated anti-proliferative and pro-apoptotic effects in certain cancers, but the response is not ubiquitous. While most responses are anti-inflammatory, glucocorticoids have been shown to positively regulate nod-like receptor pyrin containing domain 3 (NLRP3), an important proponent of pyroptotic responses. Recently, researchers have explored using pyroptotic pathways as a means of killing cancer cells, as multiple mutations that could be acquired by cancer cells are along apoptotic response pathways. Available protocols using microbial toxins lipopolysaccharide (LPS) and nigericin sodium salt to induce pyroptosis in cells have been well optimized. When applied to cancer cell lines, there is variability among the overall success of pyroptotic induction, but shows great promise and requires further research. I aim to understand if chronic exposure to glucocorticoids will prime cancer cells (A549 lung cancer cells) toward the pyroptotic response or grant them an anti-inflammatory effect. Cells exposed to glucocorticoids slowed in proliferation and adopted a more elongated morphology. Western blots measuring components of the pyroptotic response and experiments examining pyroptotic components by immunofluorescence are still underway. This work will help determine if chronic glucocorticoid users with cancer could have their cancer cells sensitized to pyroptosis, as they are already attempting to manage alternative inflammatory diseases with the drug. Alternatively, this information could help determine if there is a more anti-inflammatory effect granted and if it becomes more difficult to kill the cancerous cells using pyroptotic pathways in patients being treated with glucocorticoids.