Ergosterol peroxide from marine fungus Phoma sp. induces ROS-dependent apoptosis and autophagy in human lung adenocarcinoma cells

Abstract

As part of our ongoing search for novel therapeutic structures from microorganism, the chemical examination of marine fungus Phoma sp. resulted in the isolation of ergosterol, ergosterol peroxide (EP), and 9,11-dehydroergosterol peroxide (DEP). The bioassay results demonstrated that the three isolates reduced the viability of various cancer cells, with EP being highest in human lung cancer cell line A549 cells. EP induced caspase-dependent apoptosis through mitochondrial damage in A549 cells. Additionally, EP-induced ROS generation and apoptosis were attenuated by ROS-generating enzymes inhibitors and antioxidant N-acetylcysteine, indicated that ROS played an important role in EP-mediated apoptosis in A549 cells. Furthermore, it was observed that EP induced ROS-dependent autophagy, which attenuated apoptosis in A549 cells. On the other hand, EP reduced the LPS/ATP-induced proliferation and migration of A549 cells through attenuated NLRP3 inflammasome activity. Additionally, EP showed synergistic cytotoxic effect with antitumor drug Sorafenib in A549 cell viability inhibition. Furthermore, Micro-Western Array and Western blot analyses demonstrated that the protein levels of EGFR, HSP27, MEK5, AKT1, mTOR, Smad2, Smad3, TAB1, NF-κB, and HIF1-α decreased, while the levels of p-p38α, p-ERK1/2, p-JNK, fibronectin and p27 increased. Collectively, the results of this study demonstrated that EP might be useful to develop a therapeutic candidate for lung cancer complications.

Effects of Origanum vulgare essential oil and its two main components, carvacrol and thymol, on the plant pathogen Botrytis cinerea

“…Reactive oxygen species (highly potent oxidants containing oxygen) encompasses oxygen free radicals and nonradical oxidants, can be interconverted from one to another by enzymatic and nonenzymatic mechanisms. A large amount of ROS can lead to oxidative damage of DNA base in cells and affect various redox reactions intra-and extracellular processes (Zorov, Juhaszova & Sollott, 2014), and play an important role in cell apoptosis (Wu et al, 2018). By using fluorescent dye DCFH-DA and flow cytometer, there was increased ROS intensity in Aspergillus flavus after the treatment of Anethum graveolens L. EO at different doses (Tian et al, 2012).…”

Natural Bioactive Compounds from Fungi as Potential Candidates for Protease Inhibitors and Immunomodulators to Apply for Coronaviruses

“…Antrodia cinnamomea, a medicinal mushroom, produced antrodins A-E. Antrodins A showed potent inhibitory capabilities of HCV protease activity [97]. Five products that were obtained from the endophytic fungus Emericella nidulans, namely cordycepin, emericellin, ergosterol peroxide, myristic acid, and sterigmatocystin, reported having HCV NS3/4A protease inhibitory properties [98][99][100][101][102]. Moreover, Ahmed et al [103] isolated the metabolite compounds for HCV NS3/4A protease inhibitors that were obtained from Aspergillus versicolor that possess constituents of (−)-curvularin, cyclo(L-Pro-L-Ile), cyclo(L-Tyr-LPro), cyclo(L-Phe-L-Pro), cyclic tetrapeptide, and cyclo-(Phenylalanyl-pro-Leu-pro).…”

Inhibition of JNK-Mediated Autophagy Promotes Proscillaridin A- Induced Apoptosis via ROS Generation, Intracellular Ca+2 Oscillation and Inhibiting STAT3 Signaling in Breast Cancer Cells

“…The evidences suggest that calciuminduced-ER stress is the suitable condition for initiation of autophagy (Shi et al, 2011). Moreover, ROS-dependent autophagy has previously been well-noticed in various cancers (Wu et al, 2018;Yang et al, 2018). Therefore, we were interested to explore whether PSD-A induced autophagy is ROS and Ca +2dependent.…”