Curcumin-induced autophagy and nucleophagy in Spodoptera frugiperda Sf9 insect cells occur via PI3K/AKT/TOR pathways

J Cell Biochem. 2019 Feb;120(2):2119-2137. doi: 10.1002/jcb.27520. Epub 2018 Sep 22.

Abstract

Compounds from plants or microbes are important resources for new natural pesticides against a wide variety of pests. The growing attention on the role of autophagy (type II cell death) in regulation of insect toxicology has propelled researchers to investigate autophagic cell death pathways. Our previous study proved that the cytotoxic effect of curcumin in Spodoptera frugiperda cells is regulated by autophagy. However, the signaling pathways and molecular mechanisms had not been determined. The current study elucidates curcumin inhibition of survival signaling by blocking the activation of PI3K/AKT/TOR pathways to induce autophagy in S. frugiperda cells. The result demonstrates that nucleophagy associated with cell death following the curcumin treatment. Following the curcumin treatment, Atg8/LC3 immunostaining in both nucleus and cytoplasm was markedly increased. Further, messenger RNA expression level of Atg8 and Atg1 genes regulation by curcumin was examined using quantitative reverse transcription polymerase chain reaction, and the result exhibited increased level of expression after curcumin treatment in a time-dependent manner. Our current study provides new insights to the autophagy occurring via PI3K/AKT/TOR pathways in S. frugiperda Sf9 insect cells induced by curcumin. Taken together, our results show for the first time that curcumin induced nucleophagy in lepidopteron insect cell line.

Keywords: ATG8; PI3K/AKT/TOR; Spodoptera frugiperda-cultured cell line Sf9; autophagy; botanical pesticide; curcumin; mitophagy; nucleophagy.