Abstract | BACKGROUND & OBJECTIVES: Search for novel compounds beneficial to the treatment of cancer attracts a great deal of attention. We earlier demonstrated the isolation of 5,7-dihydroxy-2-[4'-hydroxy-3'-(methoxymethyl)phenyl]-6-C-β-glucopyranosyl flavone, a novel C-glycosyl flavone from Urginea indica bulb. The present study was undertaken to investigate the effect of this novel compound on human normal epithelial and breast, hepatic and colon cancer cell lines. METHODS: RESULTS: : Flow cytometry analysis demonstrated G0/G1 arrest. In silico docking studies predicted CDK1 and CDK6 as a possible target of C-glycosyl flavone. In vitro study confirmed CDK6 as the main target in C-glycosyl flavone-treated cancer cell lines. C-glycosyl flavone treatment also induced membrane blebbing, chromatin fragmentation and nucleosome formation. C-glycosyl flavone treatment caused marked loss of mitochondrial membrane potential, decrease in Bcl2/BAX ratio and activation of caspase-3 and release of caspase-9 and cytochrome c. In addition, C-glycosyl flavone inhibited the tumour-induced angiogenesis and reduced the vascular endothelial growth factor levels. Similarly, CDK6 inhibitor significantly inhibited proliferation and angiogenesis and induced apoptosis in tested cell lines. INTERPRETATION & CONCLUSIONS: The results indicate that C-glycosyl flavone may exert induction of apoptosis, cell cycle arrest and inhibition of angiogenesis via CDK6. Thus, targeting CDK6 using C-glycosyl flavone may serve as a novel therapeutic approach for the treatment of breast, hepatic and colon cancers.
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Authors | Ganesh Babu Bevara, A D Naveen Kumar, K Laxmi Koteshwaramma, Anil Badana, Seema Kumari, Rama Rao Malla |
Journal | The Indian journal of medical research
(Indian J Med Res)
Vol. 147
Issue 2
Pg. 158-168
(Feb 2018)
ISSN: 0971-5916 [Print] India |
PMID | 29806604
(Publication Type: Journal Article)
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Chemical References |
- Flavones
- CDK6 protein, human
- Cyclin-Dependent Kinase 6
- flavone
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Topics |
- Apoptosis
(drug effects)
- Breast Neoplasms
(drug therapy, pathology)
- Cell Cycle
(drug effects)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Colonic Neoplasms
(drug therapy)
- Cyclin-Dependent Kinase 6
(genetics)
- Drimia
(chemistry)
- Female
- Flavones
(administration & dosage, chemistry, isolation & purification)
- Gene Expression Regulation, Neoplastic
(drug effects)
- Humans
- Liver Neoplasms
(drug therapy, pathology)
- Neovascularization, Pathologic
(drug therapy, genetics, pathology)
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