Authors:

Shauna Giroir

Date Created:

Not specified

Course Title:

Professor:

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About Paper:

Breast cancer (BCa) remains a leading cause of mortality among women, with 2.3 million new cases resulting in over 670,000 global deaths annually. Despite advancements in early diagnosis and treatment, resistance and metastatic spread continue to pose significant challenges. The MDA-MB-231 cell line, a late-stage, triple-negative, highly invasive human breast cancer model, is often used to study these issues. A promising therapeutic target is the peroxisome proliferator-activated receptor (PPAR), a transcription factor with subtypes expressed in BCa cells. Activation of PPAR-γ has demonstrated tumor- suppressing effects and potential to inhibit BCa progression, while its action on cellular metabolic activity may support combination therapy with conventional chemotherapeutic agents. While PPAR agonists are clinically approved for diabetes, their toxicity has prompted the investigation of various derivatives that target other subtypes. Their antitumor activity and molecular mechanisms are largely unknown. This study evaluated the antitumor efficacy of the PPAR-γ agonist pioglitazone (PIO) and a novel partial agonist on MDA-MB-231 cells at varying concentrations. The potency (IC50) of each compound was determined, and protein expression was validated by immunoblotting to confirm the expression of known metabolic targets of PIO in BCa cells. Samples were also collected for transcriptomic analysis (RNA-seq). These data suggest that PIO and analogs show some antitumor activity but, more importantly, may modulate cellular metabolism and other pathways that enhance conventional anticancer agents. Future work will involve testing these combinations in drug-resistant MDA-MB-231 cells and utilizing three-dimensional spheroids to create more physiological models of BCa. Additionally, RNA-seq analysis will provide deeper insight into the gene expression responses of MDA-MD-231 cells to PPAR agonists, potentially identifying novel therapeutic targets.

Source:

Auburn University / College of Sciences and Mathematics / 2025

Topics:

No topics listed

Co-authors:

Shauna Giroir