PUBLICATION
Xanthatin Selectively Targets Retinoblastoma by Inhibiting the PLK1-Mediated Cell Cycle
- Authors
- Yang, J., Li, Y., Zong, C., Zhang, Q., Ge, S., Ma, L., Fan, J., Zhang, J., Jia, R.
- ID
- ZDB-PUB-211214-58
- Date
- 2021
- Source
- Investigative ophthalmology & visual science 62: 11 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Antineoplastic Agents, Phytogenic/therapeutic use*
- Apoptosis/drug effects
- Blotting, Western
- Cell Cycle/drug effects*
- Cell Cycle Proteins/antagonists & inhibitors*
- Cell Cycle Proteins/genetics
- Cell Line, Tumor
- Cell Proliferation/drug effects
- Cell Survival
- Drug Screening Assays, Antitumor
- Furans/therapeutic use*
- Humans
- Protein Serine-Threonine Kinases/antagonists & inhibitors*
- Protein Serine-Threonine Kinases/genetics
- Proto-Oncogene Proteins/antagonists & inhibitors*
- Proto-Oncogene Proteins/genetics
- RNA, Messenger/genetics
- RNA, Small Interfering/genetics
- Real-Time Polymerase Chain Reaction
- Retinal Neoplasms/drug therapy*
- Retinal Neoplasms/enzymology
- Retinal Neoplasms/pathology
- Retinoblastoma/drug therapy*
- Retinoblastoma/enzymology
- Retinoblastoma/pathology
- Signal Transduction/drug effects
- Sincalide/metabolism
- PubMed
- 34901994 Full text @ Invest. Ophthalmol. Vis. Sci.
Citation
Yang, J., Li, Y., Zong, C., Zhang, Q., Ge, S., Ma, L., Fan, J., Zhang, J., Jia, R. (2021) Xanthatin Selectively Targets Retinoblastoma by Inhibiting the PLK1-Mediated Cell Cycle. Investigative ophthalmology & visual science. 62:11.
Abstract
Purpose Retinoblastoma is the most common primary intraocular malignant tumor in children. Although intra-arterial chemotherapy and conventional chemotherapy have become promising therapeutic approaches for advanced intraocular retinoblastoma, the side effects threaten health and are unavoidable, making the development of targeted therapy an urgent need. Therefore, we intended to find a potential drug for human retinoblastoma by screening an in-house compound library that included 89 purified and well-characterized natural products.
Methods We screened a panel of 89 natural products in retinoblastoma cell lines to find the inhibitor. The inhibition of the identified inhibitor xanthatin on cell growth was detected through half-maximal inhibitory concentration (IC50), flow cytometry assay, and zebrafish model system. RNA-seq further selected the target gene PLK1.
Results We reported the discovery of xanthatin as an effective inhibitor of retinoblastoma. Mechanistically, xanthatin selectively inhibited the proliferation of retinoblastoma cells by inducing cell cycle arrest and promoting apoptosis. Interestingly, xanthatin targeted PLK1-mediated cell cycle progression. The efficacy of xanthatin was further confirmed in zebrafish models.
Conclusions Collectively, our data suggested that xanthatin significantly inhibited tumor growth in vitro and in vivo, and xanthatin could be a potential drug treatment for retinoblastoma.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping