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Role of AMPK and PPARα in the anti‐skin cancer effects of ursolic acid
Author(s) -
Junco Jacob J.,
Cho Jiyoon,
Mancha Anna,
Malik Gunjan,
Wei SungJen,
Kim Dae Joon,
Liang Huiyun,
DiGiovanni John,
Slaga Thomas J.
Publication year - 2018
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22890
Subject(s) - ursolic acid , ampk , biology , cancer cell , peroxisome proliferator activated receptor , cancer , pharmacology , protein kinase a , kinase , cancer research , cytotoxic t cell , peroxisome , receptor , biochemistry , in vitro , botany , genetics
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.