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  3. Chikusetsusaponin IVa methyl ester induces cell cycle arrest by the inhibition of nuclear translocation of β-catenin in HCT116 cells

Chikusetsusaponin IVa methyl ester induces cell cycle arrest by the inhibition of nuclear translocation of β-catenin in HCT116 cells

  • Biochem Biophys Res Commun. 2015 Apr 17;459(4):591-6. doi: 10.1016/j.bbrc.2015.02.152.
Kyung-Mi Lee 1,  Ji Ho Yun 2,  Dong Hwa Lee 3,  Young Gyun Park 2,  Kun Ho Son 3,  Chu Won Nho 4,  Yeong Shik Kim 5
Affiliations

Affiliations

  • 1 Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
  • 2 Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, 210-340, Republic of Korea.
  • 3 Department of Food Science and Nutrition, Andong National University, Andong 760-749, Republic of Korea.
  • 4 Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, 210-340, Republic of Korea. Electronic address: cwnho@kist.re.kr.
  • 5 Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Republic of Korea. Electronic address: kims@snu.ac.kr.
PMID: 25749342 DOI: 10.1016/j.bbrc.2015.02.152
Abstract

We demonstrate that chikusetsusaponin IVa methyl ester (CME), a triterpenoid saponin from the root of Achyranthes japonica, has an Anticancer activity. We investigate its molecular mechanism in depth in HCT116 cells. CME reduces the amount of β-catenin in nucleus and inhibits the binding of β-catenin to specific DNA sequences (TCF binding elements, TBE) in target gene promoters. Thus, CME appears to decrease the expression of cell cycle regulatory proteins such as Cyclin D1, as a representative target for β-catenin, as well as CDK2 and CDK4. As a result of the decrease of the cell cycle regulatory proteins, CME inhibits cell proliferation by arresting the cell cycle at the G0/G1 phase. Therefore, we suggest that CME as a novel Wnt/β-catenin Inhibitor can be a putative agent for the treatment of colorectal cancers.

Keywords

Apoptosis; Cell cycle arrest; Chikusetsusaponin IVa methyl ester; Wnt; β-catenin.

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