Nanopharmaceutical Approach for Enhanced Anti-cancer Activity of Betulinic Acid in Lung-cancer Treatment via Activation of PARP: Interaction with DNA as a Target -Anti-cancer Potential of Nano-betulinic Acid in Lung Cancer
| Autor: | Sreemanti Das, Jayeeta Das, Asmita Samadder, Avijit Paul, Anisur Rahman Khuda-Bukhsh |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
mice Poly ADP ribose polymerase lcsh:Medicine 02 engineering and technology law.invention 03 medical and health sciences chemistry.chemical_compound betulinic acid In vivo Confocal microscopy law Betulinic acid A549 cell line Cytotoxicity lcsh:Miscellaneous systems and treatments drug-DNA interaction Pharmacology A549 cell lcsh:R lcsh:RM1-950 021001 nanoscience & nanotechnology lcsh:RZ409.7-999 Molecular biology In vitro poly (lactide-co-glycolide) 030104 developmental biology lcsh:Therapeutics. Pharmacology Complementary and alternative medicine chemistry Biochemistry Apoptosis 0210 nano-technology |
| Zdroj: | Journal of Pharmacopuncture, Vol 19, Iss 1, Pp 37-44 (2016) |
| ISSN: | 2234-6856 2093-6966 |
| Popis: | Objectives This study examined the relative efficacies of a derivative of betulinic acid (dBA) and its poly (lactide- co-glycolide) (PLGA) nano-encapsulated form in A549 lung cancer cells in vivo and in co-mutagen [sodium arsenite (SA) + benzo]undefined[a]pyrene (BaP)]-induced lung cancer in mice in vivo. Methods dBA was loaded with PLGA nanoparticles by using the standard solvent displacement method. The sizes and morphologies of nano-dBA (NdBA) were determined by using transmission electron microscopy (TEM), and their intracellular localization was verified by using confocal microscopy. The binding and interaction of NdBA with calf thymus deoxyribonucleic acid (CT-DNA) as a target were analyzed by using conventional circular dichroism (CD) and melting temperature (Tm) profile data. Apoptotic signalling cascades in vitro and in vivo were studied by using an enzyme-linked immunosorbent assay (ELISA); the ability of NdBA to cross the blood-brain barrier (BBB) was also examined. The stage of cell cycle arrest was confirmed by using a fluorescence-activated cell-sorting (FACS) data analysis. Results The average size of the nanoparticles was ~ 110 nm. Confocal microscopy images confirmed the presence of NdBA in the cellular cytoplasm. The bio-physical properties of dBA and NdBA ascertained from the CD and the Tm profiles revealed that NdBA had greater interaction with the target DNA than dBA did. Both dBA and NdBA arrested cell proliferation at G0/G1, NdBA showing the greater effect. NdBA also induced a greater degree of cytotoxicity in A549 cells, but it had an insignificant cytotoxic effect in normal L6 cells. The results of flow cytometric, cytogenetial and histopathological studies in mice revealed that NdBA caused less nuclear condensation and DNA damage than dBA did. TEM images showed the presence of NdBA in brain samples of NdBA fed mice, indicating its ability to cross the BBB. Conclusion Thus, compared to dBA, NdBA appears to have greater chemoprotective potential against lung cancer. |
| Databáze: | OpenAIRE |
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