The tumor suppressor protein Par-4, which is secreted by normal cells, selectively induces apoptosis in cancer cells. We identified a 3-arylquinoline derivative, designated Arylquin 1, as a potent Par-4 secretagogue in cell cultures and mice. Mechanistically, Arylquin 1 binds to vimentin, displaces Par-4 from vimentin for secretion and triggers the efficient paracrine apoptosis of diverse cancer cells. Thus, targeting vimentin with Par-4 secretagogues efficiently induces paracrine apoptosis of tumor cells.

Partially neutralized Al solutions with OH/Al molar (ñ) ratios ranging from 0.25 to 2.5 were studied employing 27Al nuclear magnetic resonance spectroscopy and the ferron‐timed colorimetric assay. The monomeric Al concentrations (Ala) estimated by the ferron assay were consistently higher than the actual concentration determined by NMR spectroscopy. The differences between the methods indicate the presence of a small polymer which reacts rapidly with ferron and is erroneously assigned to the monomeric Al fraction. The polymeric Al component (Alb) estimated by the ferron method could be partitioned into a more rapidly reacting fraction (≤1 h) and a slowly reacting fraction (>1 h). The amount of Al associated with the rapidly reacting polymeric fraction corresponded to the amount of [AlO4 Al12(OH)24(H2O)12]7+ polymer directly determined by NMR spectroscopy. The slower reacting component of the Alb fraction is believed to be a polymer of the hexameric ring morphology. Direct NMR measurements provided evidence for specific adsorption of Al13 to a cation exchange resin and differential precipitation kinetics of this polymer with added sulfate. These data indicate that characterizing hydroxy Al solutions without direct measurements can lead to erroneous interpretations concerning the distribution between monomeric and polymeric Al and the nature and types of polymeric Al present.

The polyether toxin, okadaic acid, causes diarrhetic shellfish poisoning in humans. Despite extensive research into its cellular targets using rodent models, we know little about its putative effect(s) on innate immunity. We inoculated larvae of the greater wax moth, Galleria mellonella, with physiologically relevant doses of okadaic acid by direct injection into the haemocoel (body cavity) and/or gavage (force-feeding). We monitored larval survival and employed a range of cellular and biochemical assays to assess the potential harmful effects of okadaic acid. Okadaic acid at concentrations ≥ 75 ng/larva (≥ 242 μg/kg) led to significant reductions in larval survival (> 65%) and circulating haemocyte (blood cell) numbers (> 50%) within 24 h post-inoculation. In the haemolymph, okadaic acid reduced haemocyte viability and increased phenoloxidase activities. In the midgut, okadaic acid induced oxidative damage as determined by increases in superoxide dismutase activity and levels of malondialdehyde (i.e. lipid peroxidation). Our observations of insect larvae correspond broadly to data published using rodent models of shellfish-poisoning toxidrome, including complementary LD 50 values: 206–242 μg/kg in mice, ~ 239 μg/kg in G . mellonella . These data support the use of this insect as a surrogate model for the investigation of marine toxins, which offers distinct ethical and financial incentives. Electronic supplementary material The online version of this article (10.1007/s10565-018-09448-2) contains supplementary material, which is available to authorized users.

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