MIP-2A is a novel target of an anilinoquinazoline derivative for inhibition of tumour cell proliferation

Mayuko Tokunaga; Hirokazu Shiheido; Noriko Tabata; Yuko Sakuma-Yonemura; Hideaki Takashima; Kenichi Horisawa; Nobuhide Doi; Hiroshi Yanagawa

doi:10.1371/journal.pone.0076774

MIP-2A is a novel target of an anilinoquinazoline derivative for inhibition of tumour cell proliferation

PLoS One. 2013 Sep 30;8(9):e76774. doi: 10.1371/journal.pone.0076774. eCollection 2013.

Authors

Mayuko Tokunaga¹, Hirokazu Shiheido, Noriko Tabata, Yuko Sakuma-Yonemura, Hideaki Takashima, Kenichi Horisawa, Nobuhide Doi, Hiroshi Yanagawa

Affiliation

¹ Department of Biosciences and Informatics, Keio University, Yokohama, Japan.

Abstract

We recently identified a novel anilinoquinazoline derivative, Q15, as a potent apoptosis inducer in a panel of human cancer cell lines and determined that Q15 targets hCAP-G2, a subunit of condensin II complex, leading to abnormal cell division. However, whether the defect in normal cell division directly results in cell death remains unclear. Here, we used an mRNA display method on a microfluidic chip to search for other Q15-binding proteins. We identified an additional Q15-binding protein, MIP-2A (MBP-1 interacting protein-2A), which has been reported to interact with MBP-1, a repressor of the c-Myc promoter. Our results indicate that Q15 inhibits the interaction between MIP-2A and MBP-1 as well as the expression of c-Myc protein, thereby inducing cell death. This study suggests that the simultaneous targeting of hCAP-G2 and MIP-2A is a promising strategy for the development of antitumor drugs as a treatment for intractable tumours.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphatases / metabolism
Amino Acid Sequence
Aniline Compounds / chemistry
Aniline Compounds / metabolism
Aniline Compounds / pharmacology*
Antineoplastic Agents / chemistry
Antineoplastic Agents / metabolism
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Cell Line, Tumor
Cell Proliferation / drug effects*
DNA-Binding Proteins / metabolism
Gene Expression Profiling
Humans
Membrane Transport Proteins / metabolism*
Microfluidic Analytical Techniques
Molecular Sequence Data
Molecular Structure
Multiprotein Complexes / metabolism
Quinazolines / chemistry
Quinazolines / metabolism
Quinazolines / pharmacology*
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors / metabolism*

Substances

Aniline Compounds
Antineoplastic Agents
DENND4A protein, human
DNA-Binding Proteins
Membrane Transport Proteins
Multiprotein Complexes
Quinazolines
TRAPPC2 protein, human
Transcription Factors
condensin complexes
Adenosine Triphosphatases

Grants and funding

This work was supported by grants for a basic research program (CREST) of the Japan Science and Technology Agency and a program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO), Japan, as well as a Grant-in-Aid for Scientific Research (22310121) and a grant for Strategic Research Foundation Grant-aided Projects for Private Universities (S0801008 and S0901009) from Ministry of Education, Culture, Sport, Science, and Technology (MEXT), Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.