Extract of Dendropanax morbiferus H.Lév. Leaves Induces Apoptosis in Human Lung Carcinoma A549 Cells

Dendropanax morbiferus H.Lév. has been used in traditional medicine for the treatment of skin diseases, migraine, dysmenorrhea and other maladies.Recent studies have reported that extract of Dendropanax morbiferus H.Lév. has an anti-tumor effect on several types of cancer cells in vitro.In this study, we investigated the anticancer effects and molecular mechanisms of extracts of Dendropanax morbiferus H. Lév.(DPL) in human lung carcinoma.In vitro studies were performed using the MTT assay, DAPI staining, flow cytometry and western blot.In vivo studies were performed on four-week-old female BALB/c nude mice using xenografts and oral administration, terminal deoxynucleotidyl transferase dUTP nick end labeling, immunohistochemistry, hematoxylin and eosin.The viability of A549 lung carcinoma cells assessed by MTT assay decreased in a concentration-dependent manner from 300 μg/mL.DAPI staining revealed that DNA fragmentation significantly increased in a concentration-dependent manner, indicating apoptosis.Flow cytometry revealed that apoptosis was increased in a dose-dependent manner following treatment with DPL.Western blotting revealed that the protein levels of Bax, cleaved-poly (ADP-ribose) polymerase, and phospho-p38 increased while those of B-cell lymphoma 2 decreased.In addition, levels of phosphorylated ERK1/2 and p-c-Jun N-terminal kinases were significantly different from the control.We also investigated the in vivo effects of DPL on tumor growth.Tumor size decreased in cells treated with 500 mg/kg DPL compared with the control group in vivo.Apoptosis, assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling, was significantly increased, and the inhibitory effect on tumors was confirmed.Immunohistochemistry staining showed increased expression of phospho-p38 in the 500 mg/kg-treated group.The results indicate that DPL induced apoptosis through the p38 mitogen-activated protein kinase signaling pathway in A549 cells.