Cantharidin Impedes Activity of Glutathione S-Transferase in the Midgut of Helicoverpa armigera Hübner

Abstract

Previous investigations have implicated glutathione S-transferases (GSTs) as one of the major reasons for insecticide resistance. Therefore, effectiveness of new candidate compounds depends on their ability to inhibit GSTs to prevent metabolic detoxification by insects. Cantharidin, a terpenoid compound of insect origin, has been developed as a bio-pesticide in China, and proves highly toxic to a wide range of insects, especially lepidopteran. In the present study, we test cantharidin as a model compound for its toxicity, effects on the mRNA transcription of a model Helicoverpa armigera glutathione S-transferase gene (HaGST) and also for its putative inhibitory effect on the catalytic activity of GSTs, both in vivo and in vitro in Helicoverpa armigera, employing molecular and biochemical methods. Bioassay results showed that cantharidin was highly toxic to H. armigera. Real-time qPCR showed down-regulation of the HaGST at the mRNA transcript ranging from 2.5 to 12.5 folds while biochemical assays showed in vivo inhibition of GSTs in midgut and in vitro inhibition of rHaGST. Binding of cantharidin to HaGST was rationalized by homology and molecular docking simulations using a model GST (1PN9) as a template structure. Molecular docking simulations also confirmed accurate docking of the cantharidin molecule to the active site of HaGST impeding its catalytic activity.

Transcription factors CncC/Maf and AhR/ARNT coordinately regulate the expression of multiple GSTs conferring resistance to chlorpyrifos and cypermethrin inSpodoptera exigua

“…It has been well demonstrated that insect GSTs are a superfamily of multifunctional enzymes that are involved in the detoxification of endogenous and xenobiotic compounds, including insecticides . The HZ16 strain has significantly higher GST activity than the Sus strain (Fig.…”

Enhanced toxicity of Cry2Ab with cantharidin and its analogues on Mythimna separata

“…GSTs are synthesized with a detoxifying function because cantharidin could impede the GST catalytic activity of H. armigera (Khan et al. ). GSTs significantly increase the process of detoxification, as they possibly act as a binding protein with cantharidin and its analogues in a defence‐like response to toxicants (Bajsa et al.…”

“…; Khan et al. ). Larvae that are exposed to Bt toxins exhibit a reduction in ACP, ALP and GST (Nathan et al.…”

“…A characteristic of larvae feed with cantharidin is that the activities of acid phosphatase (ACP), alkaline phosphatase (ALP), carboxyl esterase (CarE) and glutathione S-transferase (GST) are inhibited or activated, respectively (Zhang et al 2000;Ma et al 2010;Khan et al 2013). Larvae that are exposed to Bt toxins exhibit a reduction in ACP, ALP and GST (Nathan et al 2004;Mansouri et al 2013;Wu et al 2016).…”

Cantharidin: natural bioactive molecule with a long history

“…Kantaridin vyvolává apoptózu buněk a účinně aktivuje ERK-1/2, p38 a JNK u modelových buněčných linií U937 [42]. Inhibuje také rodinu enzymů zvaných glutathion S-transferázy [43], které katalyzují konjugaci redukovaného glutathionu s řadou hydrofobních látek, obsahujících elektrofilní centrum. Tyto enzymy hrají důležitou úlohu v detoxikaci různých xenobiotik.…”