H9 Inhibits Tumor Growth and Induces Apoptosis via Intrinsic and Extrinsic Signaling Pathway in Human Non-Small Cell Lung Cancer Xenografts

Abstract

H9, a novel herbal extract, demonstrated cytotoxicity in A549 non-small cell lung cancer (NSCLC) cell lines. In this study, we investigated whether H9, and/or co-treatment with an anticancer drug, pemetrexed (PEM), inhibited tumor growth in BALB/c nude mice models bearing A549 NSCLC cells. The mice were separated into groups and administered H9 and PEM for 2 weeks. Protein and mRNA levels were detected using western blotting and reverse transcription polymerase chain reaction, respectively; immunohistochemistry (IHC) was also performed on the tumor tissues. H9 and co-treatment with PEM induced the cleavage of proapoptotic factors, such as caspase-3, caspase-8, caspase-9, and poly(ADP)-ribose polymerase (PARP). Expression levels of cell-death receptors involving Fas/FasL, TNF-related apoptosisinducing ligands (TRAIL), and TRAIL receptors were increased by H9 and co-treatment with PEM. Furthermore, analysis of levels of cell-cycle modulating proteins indicated that tumor cells were arrested in the G1/S phase. In addition, the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt survival signaling pathways were inhibited by H9 and co-treatment with PEM. In conclusion, H9 and co-treatment with PEM inhibited tumor growth in BALB/c nude mice models bearing A549 NSCLC cells. These results indicate that H9 and co-treatment with PEM can be used as an anticancer therapy in NSCLC.

The Novel Small Molecule STK899704 Promotes Senescence of the Human A549 NSCLC Cells by Inducing DNA Damage Responses and Cell Cycle Arrest

“…Male BALB/c nude mice (5 weeks old) were purchased from Nara Biotech Co., Ltd. (Seoul, South Korea). After 1 week of acclimation, the mice ( n = 4 in each group) were inoculated subcutaneously in the back with a suspension (5.0 × 10 6 cells/100 μl) of A549 cells as previously described ( Kim et al, 2015 ). The length ( a ) and width ( b ) of the tumor masses were measured twice a week.…”

Crosstalk between Autophagy and Apoptosis: Potential and Emerging Therapeutic Targets for Cardiac Diseases

“…Apoptosis is a process characterized by chromatin condensation, nuclear shrinkage and apoptosis body production [ 31 ]. The apoptotic signaling cascade mainly includes two pathways, intrinsic and extrinsic, and it gets triggered by different mitochondrial stimuli or by molecules binding to the cell-membrane receptor [ 32 , 33 ]. The intrinsic apoptosis signaling is induced by various stimuli, such as hypoxia [ 34 ], DNA damage [ 35 ], oxidative stress [ 36 ] and deprivation of growth factor [ 37 ].…”

Sodium tanshinone IIA sulfonate protects ARPE-19 cells against oxidative stress by inhibiting autophagy and apoptosis

“…The apoptotic signaling cascade includes two main pathways, intrinsic and extrinsic, which are triggered by different mitochondrial stimuli or by molecules binding to the cell-membrane receptor 30 . Intrinsic apoptosis signaling is induced by various stimuli, such as hypoxia, DNA damage, and oxidative stress 31 .…”