Metabolic Regulation of Invadopodia and Invasion by Acetyl-CoA Carboxylase 1 and De novo Lipogenesis

Invadopodia are membrane protrusions that facilitate matrix degradation and cellular invasion. Although lipids have been implicated in several aspects of invadopodia formation, the contributions of de novo fatty acid synthesis and lipogenesis have not been defined. Inhibition of acetyl-CoA carboxylase 1 (ACC1), the committed step of fatty acid synthesis, reduced invadopodia formation in Src-transformed 3T3 (3T3-Src) cells, and also decreased the ability to degrade gelatin. Inhibition of fatty acid synthesis through AMP-activated kinase (AMPK) activation and ACC phosphorylation also decreased invadopodia incidence. The addition of exogenous 16∶0 and 18∶1 fatty acid, products of de novo fatty acid synthesis, restored invadopodia and gelatin degradation to cells with decreased ACC1 activity. Pharmacological inhibition of ACC also altered the phospholipid profile of 3T3-Src cells, with the majority of changes occurring in the phosphatidylcholine (PC) species. Exogenous supplementation with the most abundant PC species, 34∶1 PC, restored invadopodia incidence, the ability to degrade gelatin and the ability to invade through matrigel to cells deficient in ACC1 activity. On the other hand, 30∶0 PC did not restore invadopodia and 36∶2 PC only restored invadopodia incidence and gelatin degradation, but not cellular invasion through matrigel. Pharmacological inhibition of ACC also reduced the ability of MDA-MB-231 breast, Snb19 glioblastoma, and PC-3 prostate cancer cells to invade through matrigel. Invasion of PC-3 cells through matrigel was also restored by 34∶1 PC supplementation. Collectively, the data elucidate the novel metabolic regulation of invadopodia and the invasive process by de novo fatty acid synthesis and lipogenesis

Antifungal activity of recombinant thanatin in comparison with two plant extracts and a chemical mixture to control fungal plant pathogens

Abstract The most common method for controlling plant diseases is the application of chemical pesticides and sometimes use of resistant cultivars. Due to the effects of chemical pesticides on human and environmental health, mutation in pathogens and resistance to various toxins besides the challenges with resistant cultivar production, the constant use of these methods are not recommended any longer. Thus, use of biological control agents along with the natural ingredient extracted from plants and application of peptide with antimicrobial activity, have been the focus of many researchers. In the present study, the antifungal activity of two plant extracts named Turmeric and Persian lilac in comparison with a chemical mixture and recombinant thanatin were evaluated against five following fungal plant pathogens; Geotrichum candidum, Botrytis cinerea, Rhizoctonia solani, Alternaria tenuissima and Gibberella fujikuroi. The results showed that, all treatments have antifungal activity against tested fungi. Both plant extracts were shown an acceptable antifungal activity against tested fungi but their inhibition effects was not comparable with chemical mixture. Turmeric showed a higher rate of mycelial inhibition than Persian lilac. Amongst all treatment, thanatin showed a great antifungal activity by its application at µg level under both in vitro and in vivo condition. Considering to the compatibility of thanatin with human health and environmental safety we could imagine a clear perspective for the application of this recombinant peptide in sustainable agriculture