Phloroglucinol induces apoptosis through the regulation of insulin-like growth factor 1 receptor signaling pathways in human colon cancer HT-29 cells

Kang,Mi-Hye; Kim,In-Hye; Nam,Taek-Jeong

doi:10.3892/ijo.2014.2521

Phloroglucinol induces apoptosis through the regulation of insulin-like growth factor 1 receptor signaling pathways in human colon cancer HT-29 cells

Authors:
- Mi-Hye Kang
- In-Hye Kim
- Taek-Jeong Nam
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Affiliations: Departments of Food and Life Science, Pukyong National University, Nam-gu, Busan 608-737, Republic of Korea
Published online on: June 24, 2014 https://doi.org/10.3892/ijo.2014.2521
Pages: 1036-1042
Copyright: © Kang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Phloroglucinol is a polyphenol compound with free radical scavenging, anti-inflammatory and antitumor activity. In this study, we investigated the anticancer effects of phloroglucinol on insulin-like growth factor-1 receptor (IGF-1R) signaling in HT-29 human colon cancer cells. Apoptosis was evaluated using 4',6-diamidino-2-phenylindole (DAPI) staining, which clearly demonstrated cell shrinkage and condensed nuclei. Treatment with a pan-caspase inhibitor reduced the expression of phosphatidylinositol-3-kinase (PI3K)/Akt, which could induce apoptosis through IGF-1R signaling pathways. Treatment with phloroglucinol significantly inhibited the expression of Ras, Raf, mitogen-activated protein kinase (MEK), extracellular-signal regulated kinase (ERK) phosphorylation, PI3K and Akt. Phloroglucinol also decreased mammalian target of rapamycin (mTOR) and expression of its downstream effectors p70S6 kinase and translation initiation factors elF4B and RPS6. These results demonstrate that IGF-1R activates PI3K/Akt/mTOR and Ras/ERK-MAPK downstream signaling pathways, which has important implications for understanding the roles of cell growth pathways in colon cancer cell tumorigenesis.

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