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Crinamine induces apoptosis and inhibits proliferation, migration, and angiogenesis in cervical cancer siHa cells
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Document Title
Crinamine induces apoptosis and inhibits proliferation, migration, and angiogenesis in cervical cancer siHa cells
Author
Khumkhrong P., Piboonprai K., Chaichompoo W., Pimtong W., Khongkow M., Namdee K., Jantimaporn A., Japrung D., Asawapirom U., Suksamrarn A., Iempridee T.
Name from Authors Collection
Affiliations
National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency, Pathum Thani, 12120, Thailand; Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok, 10240, Thailand
Type
Article
Source Title
Biomolecules
ISSN
2218273X
Year
2019
Volume
9
Issue
9
Open Access
All Open Access, Gold, Green
Publisher
MDPI AG
DOI
10.3390/biom9090494
Format
Abstract
Crinum asiaticum is a perennial herb widely distributed in many warmer regions, including Thailand, and is well-known for its medicinal and ornamental values. Crinum alkaloids contain numerous compounds, such as crinamine. Even though its mechanism of action is still unknown, crinamine was previously shown to possess anticancer activity. In this study, we demonstrate that crinamine was more cytotoxic to cervical cancer cells than normal cells. It also inhibited anchorage-independent tumor spheroid growth more effectively than existing chemotherapeutic drugs carboplatin and 5-fluorouracil or the CDK9 inhibitor FIT-039. Additionally, unlike cisplatin, crinamine induced apoptosis without promoting DNA double-strand breaks. It suppressed cervical cancer cell migration by inhibiting the expression of positive regulators of epithelial-mesenchymal transition SNAI1 and VIM. Importantly, crinamine also exerted anti-angiogenic activities by inhibiting secretion of VEGF-A protein in cervical cancer cells and blood vessel development in zebrafish embryos. Gene expression analysis revealed that its mechanism of action might be attributed, in part, to downregulation of cancer-related genes, such as AKT1, BCL2L1, CCND1, CDK4, PLK1, and RHOA. Our findings provide a first insight into crinamine's anticancer activity, highlighting its potential use as an alternative bioactive compound for cervical cancer chemoprevention and therapy. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
Keyword
cervical cancer | Crinamine | Crinum asiaticum | Tumor spheroid | Zebrafish
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
Funding Sponsor
Thailand Research Fund; National Nanotechnology Center; Center of Excellence for Innovation in Chemistry; Ministry of Higher Education, Science, Research and Innovation, Thailand
License
CC BY
Rights
Author
Publication Source
Scopus