Poly (lactide-co-glycolide) encapsulated extract of Phytolacca decandra demonstrates better intervention against induced lung adenocarcinoma in mice and on A549 cells.

Abstract

We tested relative efficacy of the extract of Phytolacca decandra (PD) and its PLGA nano-encapsulated form (NPD) in mice intoxicated with benzo[a]pyrene (BaP) (25 mg/kg b.w.) plus sodium-arsenite (SA) (10 mg/kg b.w.) and on A549 lung cancer cells in vitro. We characterized nanoparticles by physico-chemical and morphological studies using dynamic light scattering, scanning electron and atomic force microscopies. We also conducted FTIR and (1)H NMR studies to determine if NPD had a co-polymeric nature and analyzed drug-DNA interaction through circular dichroism spectra (CD) and melting temperature profiles (T(m)) taking calf thymus DNA as target. An oral dose of 0.3mg/kg b.w. for NPD and 30 mg/kg b.w. for PD in mice showed chemopreventive effects in regard to DNA fragmentation, comet tail length and toxicity biomarkers like ROS generation, NFκβ, p53, PARP, CYP1A1 and caspase 3. NPD showed greater effects than that by PD. Results of in vivo studies showed similar effects on A549 in regard to cell viability, DAPI and PI staining, Comet tail length, DNA fragmentation. To further confirm the biological molecule present in PD we analyzed its chromatographic fraction through mass spectroscopy, NMR and FT-IR studies and characterized it to be a tri-terpenoid, a derivative of betulinic acid with a molecular formula C(30)H(46)O(2.) Thus, overall results suggest that nano-encapsulation of PD (NPD) increases drug bioavailability and thereby has a better chemo-preventive action against lung cancer in vivo and on A549 cells in vitro than that of PD.

• Authors: Jayeeta Das, Sreemanti Das, Asmita Samadder, Kakali Bhadra, Anisur Rahman Khuda-Bukhsh
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 47 Issue 2 Pg. 313-24 (Sep 29 2012) ISSN: 1879-0720 [Electronic] Netherlands
• PMID: 22771545 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Arsenites
• Bax protein, mouse
• Carcinogens
• Drug Carriers
• Plant Extracts
• Proto-Oncogene Proteins c-bcl-2
• RNA, Messenger
• Reactive Oxygen Species
• Sodium Compounds
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• Benzo(a)pyrene
• sodium arsenite
• Cytochrome P-450 CYP1A1
• Caspase 3

Topics

• Adenocarcinoma (chemically induced, drug therapy, metabolism, pathology)
• Adenocarcinoma of Lung
• Animals
• Antineoplastic Agents (administration & dosage, chemistry)
• Arsenites (toxicity)
• Benzo(a)pyrene (toxicity)
• Carcinogens (toxicity)
• Caspase 3 (genetics, metabolism)
• Cell Line, Tumor
• Cells, Cultured
• Cytochrome P-450 CYP1A1 (biosynthesis, genetics)
• DNA Damage (drug effects)
• Drug Carriers (administration & dosage, chemistry)
• Humans
• Lactic Acid (administration & dosage, chemistry)
• Leukocytes, Mononuclear
• Lung Neoplasms (chemically induced, drug therapy, metabolism, pathology)
• Mice
• Nanoparticles (administration & dosage, chemistry)
• Phytolacca
• Plant Extracts (administration & dosage, chemistry)
• Polyglycolic Acid (administration & dosage, chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Proto-Oncogene Proteins c-bcl-2 (genetics)
• RNA, Messenger (metabolism)
• Reactive Oxygen Species (metabolism)
• Sodium Compounds (toxicity)
• Tumor Suppressor Protein p53 (genetics, metabolism)
• bcl-2-Associated X Protein