Strong Anticancer Potential of Nano-triterpenoid from Phytolacca decandra against A549 Adenocarcinoma via a Ca 2+ -dependent Mitochondrial Apoptotic Pathway

다국어 초록 (Multilingual Abstract)

We isolated a triterpenoid from an ethanolic extract of Phytolacca decandra and na- noencapsulated 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 nano- particles 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 IC 50 doses of 50 mg/mL and 100 mg/mL, respectively. Mitochondrial dysfunction-mediated apoptosis was determined by exam- ining 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 (DJ m ) depolarization. Apoptosis was also verified by acridine or- ange staining observed under fluorescence microscopy and annexin V-fluorescein iso- thiocyanate/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 mito- chondrial oxidative phosphorylation system, with NdBA having a stronger effect, indi- cating NdBA to be a better candidate for the development of an anticancer drug for use against lung adenocarcinomas.

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