Antitumor Activity of Vanicoside B Isolated from Persicaria dissitiflora by Targeting CDK8 in Triple-Negative Breast Cancer Cells.

Abstract

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.

• Authors: Donghwa Kim, Cai Yi Wang, Ruoci Hu, Ji Yun Lee, Thi-Thu-Trang Luu, Hee-Juhn Park, Sang Kook Lee
• Journal: Journal of natural products (J Nat Prod) Vol. 82 Issue 11 Pg. 3140-3149 (11 22 2019) ISSN: 1520-6025 [Electronic] United States
• PMID: 31622095 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Cinnamates
• vanicoside B
• CDK8 protein, human
• Cyclin-Dependent Kinase 8

Topics

• Animals
• Antineoplastic Agents, Phytogenic (chemistry, pharmacology)
• Apoptosis (drug effects)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cinnamates (chemistry, metabolism, pharmacology)
• Cyclin-Dependent Kinase 8 (drug effects, metabolism)
• Drug Screening Assays, Antitumor
• Female
• Humans
• Mice
• Mice, Nude
• Molecular Structure
• Polygonaceae (chemistry)
• Triple Negative Breast Neoplasms (drug therapy, metabolism)
• Tumor Stem Cell Assay
• Xenograft Model Antitumor Assays