Ursolic acid exerts anti-cancer activity by suppressing vaccinia-related kinase 1-mediated damage repair in lung cancer cells.

Abstract

Many mitotic kinases have been targeted for the development of anti-cancer drugs, and inhibitors of these kinases have been expected to perform well for cancer therapy. Efforts focused on selecting good targets and finding specific drugs to target are especially needed, largely due to the increased frequency of anti-cancer drugs used in the treatment of lung cancer. Vaccinia-related kinase 1 (VRK1) is a master regulator in lung adenocarcinoma and is considered a key molecule in the adaptive pathway, which mainly controls cell survival. We found that ursolic acid (UA) inhibits the catalytic activity of VRK1 via direct binding to the catalytic domain of VRK1. UA weakens surveillance mechanisms by blocking 53BP1 foci formation induced by VRK1 in lung cancer cells, and possesses synergistic anti-cancer effects with DNA damaging drugs. Taken together, UA can be a good anti-cancer agent for targeted therapy or combination therapy with DNA damaging drugs for lung cancer patients.

• Authors: Seong-Hoon Kim, Hye Guk Ryu, Juhyun Lee, Joon Shin, Amaravadhi Harikishore, Hoe-Yune Jung, Hoe-Youn Jung, Ye Seul Kim, Ha-Na Lyu, Eunji Oh, Nam-In Baek, Kwan-Yong Choi, Ho Sup Yoon, Kyong-Tai Kim
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 14570 (Sep 28 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26412148 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Intracellular Signaling Peptides and Proteins
• Triterpenes
• Doxorubicin
• Protein Serine-Threonine Kinases
• VRK1 protein, human
• ursolic acid

Topics

• Animals
• Antineoplastic Agents, Phytogenic (chemistry, pharmacology)
• Binding Sites
• Catalytic Domain
• Cell Line, Tumor
• DNA Damage (drug effects)
• Disease Models, Animal
• Doxorubicin (pharmacology)
• Drug Synergism
• Enzyme Activation (drug effects)
• Humans
• Intracellular Signaling Peptides and Proteins (antagonists & inhibitors, chemistry, metabolism)
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Models, Molecular
• Molecular Conformation
• Nuclear Magnetic Resonance, Biomolecular
• Protein Binding
• Protein Interaction Domains and Motifs
• Protein Serine-Threonine Kinases (antagonists & inhibitors, chemistry, metabolism)
• Triterpenes (chemistry, pharmacology)
• Xenograft Model Antitumor Assays