Research Papers:

A small molecule, (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol suppresses tumor growth via inhibition of IkappaB kinase β in colorectal cancer in vivo and in vitro

Jie Zheng, Mi Hee Park, Hee Pom Lee, Byung Kook Hyun, Hyung Ok Chun, Sung Hee Jung, Hyun Ok Seo, Young Wan Ham, Sang-Bae Han and Jin Tae Hong _

PDF  |  HTML  |  How to cite

Oncotarget. 2017; 8:91258-91269. https://doi.org/10.18632/oncotarget.20440

Metrics: PDF 1337 views  |   HTML 1853 views  |   ?  


Jie Zheng1,3,*, Mi Hee Park1,*, Hee Pom Lee1, Byung Kook Hyun1, Hyung Ok Chun1, Sung Hee Jung1, Hyun Ok Seo1, Young Wan Ham2, Sang-Bae Han1 and Jin Tae Hong1

1College of Pharmacy & Medical Research Center, Chungbuk National University, Cheongju, Chungbuk 28160, Republic of Korea

2Department of Chemistry, Utah Valley University 800 W, University Pkwy, Orem, UT 84058, USA

3Current address: Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea

*These authors have contributed equally to this work

Correspondence to:

Jin Tae Hong, email: [email protected]

Sang-Bae Han, email: [email protected]

Keywords: MMPP, colon cancer, IKKβ, death receptor, tumor growth inhibition

Received: March 24, 2017    Accepted: July 26, 2017    Published: August 24, 2017


Here we report that a novel synthesized compound (E)-2-methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenol (MMPP) which exhibits better stability, drug-likeness and anti-cancer effect than (E)-2,4-bis(p-hydroxyphenyl)-2-butenal (BHPB) that we previously reported. Of all newly synthesized BHPB analogues, MMPP showed the most significant inhibitory effect on colon cancer cell growth. Thus, we evaluated the anti-cancer effects and possible mechanisms of MMPP in vitro and in vivo. MMPP treatment (0-15 μg/mL) induced apoptotic cell death and enhanced the expression of cleaved caspase-3 and cleaved caspase-8 in a concentration dependent manner. Notably, the expression of death receptor (DR)5 and DR6 was significantly increased by MMPP treatment. Moreover, DR5 siRNA or DR6 siRNA transfection partially abolished MMPP-induced cell growth inhibition. Pull down assay and docking experiment showed that MMPP bound directly to IkappaB kinase β (IKKβ). It was noteworthy that IKKβ mutant (C99S) partially abolished MMPP-induced cell growth inhibition and enhanced expression of DR5 and DR6. In addition, MMPP enhanced TRAIL-induced apoptosis, cell growth inhibition and expression of DRs. In xenograft mice model, MMPP (2.5-5 mg/kg) suppressed tumor growth in a dose dependent manner. Immunohistochemistry analysis showed that the expression levels of DR5 and DR6 and active caspase-3 were increased while the expression levels of PCNA and p-IKKβ were decreased in a dose dependent manner. Thus, MMPP may be a promising anti-cancer agent in colon cancer treatment.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 20440