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Bisleuconothine A, a bisindole alkaloid, inhibits colorectal cancer cell in vitro
and in vivo targeting Wnt signaling
#MMPMID26862734
Kong LM
; Feng T
; Wang YY
; Li XY
; Ye ZN
; An T
; Qing C
; Luo XD
; Li Y
Oncotarget
2016[Mar]; 7
(9
): 10203-14
PMID26862734
show ga
Wnt signaling pathway is aberrantly activated in a variety of cancers, especially
in colorectal cancer and small molecule antagonists of Wnt/?-catenin signaling
are attractive candidates for developing effective therapeutics. In the present
study, we identified Bisleuconothine A, a bisindole alkaloid with an
eburnane-aspidosperma type skeleton, as a novel and selective Wnt signaling
inhibitor by using a cell-based luciferase assay system. Our study found that
Bisleuconothine A down-regulated the endogenous Wnt target gene expression
through promoting phosphorylation of ?-catenin and the subsequent inhibition of
its nuclear translocation in HCT116 and SW480 colorectal cancer cells. In vitro,
Bisleuconothine A inhibited cell proliferation through induction of apoptosis by
increasing the cleavage of caspases in HCT116 and SW480 colorectal cancer cells.
Moreover, in vivo, Bisleuconothine A dramatically suppressed tumor growth in
HCT116 Xenograft. And further analysis showed that Bisleuconothine A suppressed
the Wnt target gene expression in HCT116 Xenograft, which was associated with
up-regulation of ?-catenin phosphorylation and subsequent Wnt signaling
inhibition. Taken together, our study indicated that bisindole alkaloids could be
included as a new chemotype of small-molecule Wnt signaling inhibitors, and have
great potential to be further developed for anti-tumor agents.
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