Chikusetsusaponin IVa methyl ester induces cell cycle arrest by the inhibition of nuclear translocation of β-catenin in HCT116 cells.
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.
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Kyung-Mi
KM
Lee
Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, 210-340, Republic of Korea.
Ji Ho
JH
Yun
Department of Food Science and Nutrition, Andong National University, Andong 760-749, Republic of Korea.
Dong Hwa
DH
Lee
Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, 210-340, Republic of Korea.
Young Gyun
YG
Park
Department of Food Science and Nutrition, Andong National University, Andong 760-749, Republic of Korea.
Kun Ho
KH
Son
Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, 210-340, Republic of Korea. Electronic address: cwnho@kist.re.kr.
Chu Won
CW
Nho
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Republic of Korea. Electronic address: kims@snu.ac.kr.
Yeong Shik
YS
Kim
D001483:Base Sequence; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D017931:DNA Primers; D004952:Esters / Q000737:chemistry; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D021381:Protein Transport; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D051176:beta Catenin / Q000378:metabolism*
D017931:DNA Primers; D004952:Esters; D012503:Saponins; D051176:beta Catenin; C098580:chikusetsu saponin IVa; D009828:Oleanolic Acid
Apoptosis; Cell cycle arrest; Chikusetsusaponin IVa methyl ester; Wnt; β-catenin