Antitumor Activity of Vanicoside B Isolated from Persicaria dissitiflora by Targeting CDK8 in Triple-Negative Breast Cancer Cells
Donghwa Kim, Cai Yi Wang, Ruoci Hu, Ji Yun Lee, Thi-Thu-Trang Luu, Hee-Juhn Park, Sang Kook Lee · Journal of Natural Products · 2019
A 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.