@article{050066eeebfb4dc5a0cf4ca115c8fabd,
title = "Role of AMPK and PPARα in the anti-skin cancer effects of ursolic acid",
abstract = "The phytonutrient ursolic acid (UA), present in apples, rosemary, and other plant sources, has anti-cancer properties in a number of systems, including skin cancers. However, few reports have examined upstream mechanisms by which UA may prevent or treat cancer. Recent reports have indicated UA induces death of cancer cell lines via AMP-activated protein kinase (AMPK), an energy-sensing kinase which possesses both pro-metabolic and anti-cancer effects. Other studies have shown UA activates peroxisome proliferator activated receptor α (PPARα) and the glucocorticoid receptor (GR). Here, we found the cytotoxic effect of UA in skin carcinoma cells required AMPK activation. In addition, two inhibitors of PPARα partially reversed the cytotoxic effects of UA, suggesting its effects are at least partially mediated through this receptor. Finally, inhibition of the GR did not reverse the effects of UA nor did this compound bind the GR under the conditions of experiments performed. Overall, studies elucidating the anti-cancer effects of UA may allow for the development of more potent analogues utilizing similar mechanisms. These studies may also reveal the mediators of any possible side effects or resistance mechanisms to UA therapy.",
keywords = "AMP-activated protein kinases, neoplasms, phytochemicals",
author = "Junco, {Jacob J.} and Jiyoon Cho and Anna Mancha and Gunjan Malik and Wei, {Sung Jen} and Kim, {Dae Joon} and Huiyun Liang and John DiGiovanni and Slaga, {Thomas J.}",
note = "Funding Information: Radioactive ligand binding experiments were performed using a MultiPurpose Scintillation Counter from Beckman Coulter provided by the Department of Pharmacology at The University of Texas Health Science Center at San Antonio. Financial Support was provided by the National Institutes of Health (R01 CA164159, P30 CA54174), a Clinical and Translational Science Award (UL1RR025767), the American Cancer Research Center and Foundation, an Oppenheimer Multi-Investigator Research Award, and a pre-doctoral fellowship from the Pharmaceutical Research and Manufacturers of America Foundation. Funding Information: National Institutes of Health, Grant numbers: P30 CA54174, R01 CA164159; Clinical and Translational Science Award, Grant number: UL1RR025767 Funding Information: Radioactive ligand binding experiments were performed using a Multi-Purpose Scintillation Counter from Beckman Coulter provided by the Department of Pharmacology at The University of Texas Health Science Center at San Antonio. Financial Support was provided by the National Institutes of Health (R01 CA164159, P30 CA54174), a Clinical and Translational Science Award (UL1RR025767), the American Cancer Research Center and Foundation, an Oppenheimer Multi-Investigator Research Award, and a pre-doctoral fellowship from the Pharmaceutical Research and Manufacturers of America Foundation.",
year = "2018",
month = dec,
doi = "10.1002/mc.22890",
language = "English (US)",
volume = "57",
pages = "1698--1706",
journal = "Molecular Carcinogenesis",
issn = "0899-1987",
publisher = "Wiley-Liss Inc.",
number = "12",
}