Chikusetsusaponin IVa methyl ester (CME) induces cell cycle arrest and apoptosis by regulation of the Wnt signalling pathway via differential mechanisms

Title
Chikusetsusaponin IVa methyl ester (CME) induces cell cycle arrest and apoptosis by regulation of the Wnt signalling pathway via differential mechanisms
Authors
이경미윤지호이동화박영균손건호노주원김영식
Keywords
Chikusetsusaponin IVa methyl ester; apoptosis; Wnt; Achyranthes japonica; cell cycle arrest
Issue Date
2014-05
Publisher
생화학분자생물학회 (KSBMB)
Abstract
Abnormal activation of Wnt signalling pathway has been known to induce colorectal cancer. We newly found that Chikusetsusaponin IVa methyl ester (CME), a triterpenoid saponin from the root of Achyranthes japonica, showed anticancer activity by inhibition of Wnt signalling pathway in colorectal cancer cells and we investigated its molecular mechanism in depth. CME induced G0/G1 phase arrest by disrupting the interaction between b-catenin and its target DNA sequences (TCF binding elements, TBE) in target gene promoters to inhibit cell cycle regulatory proteins including Cyclin D1. Moreover, CME caused the extrinsic apoptotic pathway, which is triggered by the JNK pathway. CME-induced apoptosis might be occurred by increased transcription of the secreted Frizzled-related proteins 1 (SFRP1) gene, a Wnt antagonist, hypermethylated in colorectal cancer cells. SFRP1 is reported to induce apoptosis possibly through the JNK pathway. Overall, these results demonstrated a differential mechanism for the inhibition of cell proliferation by CME in which CME induces cell cycle arrest by inhibiting cell cycle regulatory factors including Cyclin D1 and apoptosis by activating SFRP1 followed by inhibition of Wnt to induce further downstream of JNK pathway.
URI
http://pubs.kist.re.kr/handle/201004/47600
Appears in Collections:
KIST Publication > Conference Paper
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