p38α Is Required for Ovarian Cancer Cell Metabolism and Survival

• DOI: 10.1111/igc.0b013e3181c8ca12
• Publication Date: 2010-12-03T19:22:09Z
• Authors: Antonio Matrone; Valentina Grossi; Fulvio Chiacchiera; Emanuela Fina; Marianna Cappellari; Anna Maria Caring...; Edoardo Di Naro; Giuseppe Loverro; Cristiano Simone
• Keywords: Ovarian Neoplasms; 0303 health sciences; Cell Survival; Carcinoma; Forkhead Box Protein O3; Forkhead Transcription Factors; AMP-Activated Protein Kinases; Hypoxia-Inducible Factor 1, alpha Subunit; 3. Good health; Gene Expression Regulation, Neoplastic; Mitogen-Activated Protein Kinase 14; 03 medical and health sciences; Ovarian cancer, p38α, HIF1α, AMPK, FoxO3A, Autophagy; Cell Line, Tumor; Homeostasis; Humans; Female; Cell Proliferation; Signal Transduction

<h3>Introduction:</h3> Ovarian cancer is highly sensitive to chemotherapy but also shows a high rate of recurrence and drug resistance. These negative outcomes mostly depend on altered apoptotic pathways, making the design new therapeutic strategies based induction other types cell death desirable. Several lines research are now addressing cancer-specific features specifically target tumor cells, thus reducing adverse effects. In this light, great deal attention has been devoted metabolic reprogramming occurring in which display increased levels glycolysis compared with their normal counterparts. We recently showed that inhibition p38α impairs key functions colorectal inducing growth arrest, autophagy, both vivo vitro. effects mediated by switch from hypoxia-inducible factor 1α (HIF1α) forkhead transcription O (<i>FoxO</i>)-dependent transcription. <h3>Methods:</h3> first characterized <i>p38</i> expression OVCAR-3, A2780, SKOV-3 ovarian lines. Then, we treated these cells p38α/p38β-specific inhibitor SB202190 performed morphological, proliferation, survival analyses. Finally, studied HIF1α FoxO3A expressions signaling pathways evaluate role SB202190-induced <h3>Results:</h3> blockade induces formation intracellular autophagic vacuoles reduces viability cells. As cancer, underlying molecular mechanism seems rely shift HIF1α- FoxO3A-dependent transcription, promoted activation adenosine monophosphate-activated protein kinase pathway. <h3>Conclusions:</h3> data corroborate hypothesis pharmacological modulation genes involved homeostasis, such as p38α, might be exploited approaches treatment.