Murrayafoline A attenuates the Wnt/{beta}-catenin pathway by promoting the degradation of intracellular {beta}-catenin proteins

Journal Article · Thu Dec 31 23:00:00 EST 2009 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2009.11.164· OSTI ID:22199993

Choi, Hyuk; Gwak, Jungsug; Cho, Munju; Ryu, Min-Jung ^[1]; Lee, Jee-Hyun; Kim, Sang Kyum; Kim, Young Ho ^[2]; Lee, Gye Won ^[3]; Yun, Mi-Young ^[4]; Cuong, Nguyen Manh ^[5]; Shin, Jae-Gook ^[1]; Song, Gyu-Yong ^[2]; Oh, Sangtaek ^[1]

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1. PharmacoGenomics Research Center, Inje University, Busan 614-735 (Korea, Republic of)
2. College of Pharmacy, Chungnam National University, Daejeon 305-764 (Korea, Republic of)
3. Department of Pharmaceutical Engineering, Konyang University, Nonsan 320-711 (Korea, Republic of)
4. Department of Beauty Health Care, Daejeon University, Daejeon 305-764 (Korea, Republic of)
5. Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, Hanoi (Viet Nam)

Molecular lesions in Wnt/{beta}-catenin signaling and subsequent up-regulation of {beta}-catenin response transcription (CRT) occur frequently during the development of colon cancer. To identify small molecules that suppress CRT, we screened natural compounds in a cell-based assay for detection of TOPFalsh reporter activity. Murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa, antagonized CRT that was stimulated by Wnt3a-conditioned medium (Wnt3a-CM) or LiCl, an inhibitor of glycogen synthase kinase-3{beta} (GSK-3{beta}), and promoted the degradation of intracellular {beta}-catenin without altering its N-terminal phosphorylation at the Ser33/37 residues, marking it for proteasomal degradation, or the expression of Siah-1, an E3 ubiquitin ligase. Murrayafoline A repressed the expression of cyclin D1 and c-myc, which is known {beta}-catenin/T cell factor (TCF)-dependent genes and thus inhibited the proliferation of various colon cancer cells. These findings indicate that murrayafoline A may be a potential chemotherapeutic agent for use in the treatment of colon cancer.

• OSTI ID: 22199993
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 391; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ALKALOIDS
CELL PROLIFERATION
GENE REGULATION
GLYCOGEN
LARGE INTESTINE
LIGASES
LITHIUM CHLORIDES
NEOPLASMS
PHOSPHORYLATION
TRANSCRIPTION