Title:Perspectives on the Role of P21-Activated Kinase 1 (PAK1) in the Intestinal
Anti-inflammatory and Antitumor Potential of Artepillin C
Volume: 17
Author(s): Luisa Mota da Silva*
Affiliation:
- Pharmaceutical Sciences Graduate Program, University of Itajai Valley, Itajai, SC, Brazil
Keywords:
PAK1, Brazilian green propolis, Colitis-associated colorectal cancer, Arptepillin C, Tumor, Inflammation.
Abstract: The Brazilian biodiversity may bring new perspectives to the therapy of Inflammatory Bowel Diseases (IBD) and intestinal cancer. The
effect of Brazilian Green Propolis in reducing ulcerative colitis in mice has already been described, as well as high amounts of the prenylated
compound Artepellin C (ARC). The search for new pharmacological targets for IBD is also advancing. Among possibilities is the p21-activated
kinase (PAK1), overexpressed and activated in the intestinal mucosa during IBD and colitis-associated colorectal cancer (CAC). PAK 1 contributes
to tissue inflammation by reducing the expression of peroxisome proliferator-activated receptor type γ (PPAR47) and increasing activation of
nuclear factor (NF)-κB. At least in vitro, inhibition of PAK1 has been reported to mitigate NF-κB-mediated inflammation in intestinal cells and
ARC inhibits PAK1 activation. Given this pharmacological potential of ARC and the role of PAK1 in IBD and CAC, this perspective collected
information that encourages future research to test the hypothesis that ARC can maintain intestinal integrity under the inflammatory and neoplastic
stimulus and that inhibition of PAK1/NF-κB signaling and favoring PPAR-γ activity is pivotal in this action. Therefore, future studies employing
in vitro and in vivo steps, using murine and human enterocytes and rodents submitted to ulcerative colitis and CAC models are incentivized by the
data gathered here, favor retirar essas palavras: mostly in vitro studies, before clinical trials. Therefore, the perspective presented here points to an
interesting path in the search for a drug useful in inflammatory and neoplastic intestinal diseases, which may have ARC as a prototype, acting on a
target not yet explored clinically.
