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Antitumor Activity of Vanicoside B Isolated from Persicaria dissitiflora by Targeting CDK8 in Triple-Negative Breast Cancer Cells
journal contribution
posted on 2019-10-17, 16:37 authored by Donghwa Kim, Cai Yi Wang, Ruoci Hu, Ji Yun Lee, Thi-Thu-Trang Luu, Hee-Juhn Park, Sang Kook LeeA flavonoid glycoside, quercitrin
(1), and two phenylpropanoyl
sucrose derivatives, vanicoside B (2) and lapathoside
C (3), were isolated for the first time from the herb Persicaria dissitiflora. Vanicoside B (2) exhibited
antiproliferative activity against a panel of cancer cell lines in
triple-negative breast cancer (TNBC) MDA-MB-231 cells. The underlying
mechanisms of the antitumor activity of 2 were investigated
in TNBC cells. Upregulation of cyclin-dependent kinase 8 (CDK8) was
observed in a claudin-low molecular subtype of TNBC cells. A molecular
modeling study indicated that 2 showed a high affinity
for CDK8. Further investigations revealed that 2 suppressed
CDK8-mediated signaling pathways and the expression of epithelial–mesenchymal
transition proteins and induced cell cycle arrest and apoptosis in
MDA-MB-231 and HCC38 TNBC cells. Moreover, 2 inhibited
tumor growth without overt toxicity in a nude mouse xenograft model
implanted with MDA-MB-231 cells. Taken together, these findings demonstrate
the significance of CDK8 activity in TNBC and suggest a potential
use of 2 as a therapeutic candidate for the treatment
of aggressive human triple-negative breast cancer.