Lambertianic Acid Sensitizes Non-Small Cell Lung Cancers to TRAIL-Induced Apoptosis via Inhibition of XIAP/NF-κB and Activation of Caspases and Death Receptor 4

International Journal of Molecular Sciences
Deok Soo AhnSung-Hoon Kim

Abstract

Lambertianic acid (LA) is a biologically active compound from the leaves of Pinus koraiensis. In the present study, apoptotic mechanisms of LA plus TNF-related apoptosis-inducing ligand (TRAIL) were elucidated in non-small cell lung cancer cells (NSCLCs). Cytotoxicity assay, flow cytometry, immunoprecipitation, and Western blotting were performed. Here, combined treatment of LA and TRAIL increased cytotoxicity, sub-G1 population, cleaved poly (ADP-ribose) polymerase (PARP), and caspase3/8/9 in A549 and H1299 cells compared to LA or TRAIL alone. Furthermore, combined treatment of LA and TRAIL significantly decreased antiapoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Fas-like inhibitor protein (FLIP), and X-linked inhibitor of apoptosis protein (XIAP), and enhanced the activation of proapoptotic proteins Bid compared to LA or TRAIL alone. In addition, combined treatment of LA and TRAIL upregulated the expression of Death receptor 4 (DR4) and downregulated phosphorylation of nuclear factor κ-light-chain-enhancer of activated B cells (p-NF-κB), inhibitory protein of kB family (p-IκB), and FLIP in A549 and H1299 cells along with disrupted binding of XIAP with caspase3 or NF-κB. Overall, these findings suggest that lambertiani...Continue Reading

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Citations

Jan 27, 2021·Stem Cell Research & Therapy·Faroogh MarofiFarhad Motavalli Khiavi
Nov 12, 2020·International Journal of Molecular Sciences·Ming-Min ChangBu-Miin Huang
Apr 8, 2021·Zeitschrift Für Naturforschung. C, a Journal of Biosciences·Md ShahinozzamanA T M Rafiqul Islam

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Methods Mentioned

BETA
immunoprecipitation
column chromatography
nuclear magnetic resonance
protein assay

Software Mentioned

CellQuest
Sigmaplot

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