TY - JOUR
T1 - Strong Anticancer Potential of Nano-triterpenoid from Phytolacca decandra against A549 Adenocarcinoma via a Ca2+-dependent Mitochondrial Apoptotic Pathway
AU - Das, Jayeeta
AU - Das, Sreemanti
AU - Paul, Avijit
AU - Samadder, Asmita
AU - Khuda-Bukhsh, Anisur Rahman
N1 - Funding Information:
Financial assistance for the work by Boiron Laboratories, Lyon, France , is gratefully acknowledged.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - We isolated a triterpenoid from an ethanolic extract of Phytolacca decandra and nanoencapsulated it with biodegradable nontoxic polymers of poly(lactide-co-glycolide) to examine if the nanoform of this hitherto unexplored betulinic-acid derivative (NdBA) could produce a stronger anticancer effect by rendering better drug bioavailability and targeted delivery than the nonencapsulated betulinic-acid derivative (dBA). The nanoparticles were characterized with the help of physicochemical and morphological studies involving dynamic light scattering and atomic force microscopy. A549 cancer cells were exposed to NdBA and dBA at the IC50 doses of 50μg/mL and 100μg/mL, respectively. Mitochondrial dysfunction-mediated apoptosis was determined by examining the changes in the intracellular calcium content, the reactive oxygen species accumulation, the cytochrome c release, the upregulation of Bcl-2-associated-X protein (Bax) and caspase 3, the downregulation of B cell lymphoma 2, and the mitochondrial membrane potential (δΨm) depolarization. Apoptosis was also verified by acridine orange staining observed under fluorescence microscopy and annexin V-fluorescein isothiocyanate/propidium iodide staining through flow cytometric studies. The levels of intracellular adenosine triphosphate/adenosine diphosphate ratio decreased, and the ATPase activity increased more strikingly in A549 cells exposed to NdBA than in A549 cells exposed to dBA. Overall results showed that both drugs directly target the mitochondrial oxidative phosphorylation system, with NdBA having a stronger effect, indicating NdBA to be a better candidate for the development of an anticancer drug for use against lung adenocarcinomas.
AB - We isolated a triterpenoid from an ethanolic extract of Phytolacca decandra and nanoencapsulated it with biodegradable nontoxic polymers of poly(lactide-co-glycolide) to examine if the nanoform of this hitherto unexplored betulinic-acid derivative (NdBA) could produce a stronger anticancer effect by rendering better drug bioavailability and targeted delivery than the nonencapsulated betulinic-acid derivative (dBA). The nanoparticles were characterized with the help of physicochemical and morphological studies involving dynamic light scattering and atomic force microscopy. A549 cancer cells were exposed to NdBA and dBA at the IC50 doses of 50μg/mL and 100μg/mL, respectively. Mitochondrial dysfunction-mediated apoptosis was determined by examining the changes in the intracellular calcium content, the reactive oxygen species accumulation, the cytochrome c release, the upregulation of Bcl-2-associated-X protein (Bax) and caspase 3, the downregulation of B cell lymphoma 2, and the mitochondrial membrane potential (δΨm) depolarization. Apoptosis was also verified by acridine orange staining observed under fluorescence microscopy and annexin V-fluorescein isothiocyanate/propidium iodide staining through flow cytometric studies. The levels of intracellular adenosine triphosphate/adenosine diphosphate ratio decreased, and the ATPase activity increased more strikingly in A549 cells exposed to NdBA than in A549 cells exposed to dBA. Overall results showed that both drugs directly target the mitochondrial oxidative phosphorylation system, with NdBA having a stronger effect, indicating NdBA to be a better candidate for the development of an anticancer drug for use against lung adenocarcinomas.
KW - A549 lung adenoma cells
KW - Apoptosis
KW - Betulinic acid
KW - Intracellular calcium content
KW - PLGA nanoparticles
KW - Phytolacca decandra
UR - http://www.scopus.com/inward/record.url?scp=84902329973&partnerID=8YFLogxK
U2 - 10.1016/j.jams.2013.07.009
DO - 10.1016/j.jams.2013.07.009
M3 - Article
C2 - 24929458
AN - SCOPUS:84902329973
SN - 2005-2901
VL - 7
SP - 140
EP - 150
JO - JAMS Journal of Acupuncture and Meridian Studies
JF - JAMS Journal of Acupuncture and Meridian Studies
IS - 3
ER -