Crinamine Induces Apoptosis and Inhibits Proliferation, Migration, and Angiogenesis in Cervical Cancer SiHa Cells.

Abstract

Crinumasiaticum 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.

• Authors: Phattharachanok Khumkhrong, Kitiya Piboonprai, Waraluck Chaichompoo, Wittaya Pimtong, Mattaka Khongkow, Katawut Namdee, Angkana Jantimaporn, Deanpen Japrung, Udom Asawapirom, Apichart Suksamrarn, Tawin Iempridee
• Journal: Biomolecules (Biomolecules) Vol. 9 Issue 9 (09 16 2019) ISSN: 2218-273X [Electronic] Switzerland
• PMID: 31527550 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amaryllidaceae Alkaloids
• Angiogenesis Inhibitors
• FIT-039
• Plant Extracts
• Pyridines
• SNAI1 protein, human
• Snail Family Transcription Factors
• VIM protein, human
• Vimentin
• crinamine
• Carboplatin
• Fluorouracil

Topics

• Amaryllidaceae Alkaloids (administration & dosage, pharmacology)
• Angiogenesis Inhibitors (administration & dosage, pharmacology)
• Animals
• Carboplatin (pharmacology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Crinum (chemistry)
• Disease Models, Animal
• Embryo, Nonmammalian (blood supply, drug effects)
• Epithelial-Mesenchymal Transition (drug effects)
• Female
• Fluorouracil (pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• HeLa Cells
• Humans
• Plant Extracts (chemistry)
• Pyridines (pharmacology)
• Snail Family Transcription Factors (metabolism)
• Uterine Cervical Neoplasms (blood supply, drug therapy, metabolism)
• Vimentin (metabolism)
• Zebrafish (embryology)