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The antidiabetic drug metformin displays anticancer properties in several neoplasms. In pituitary NETs, aryl hydrocarbon receptor-interacting protein (AIP) is up-regulated by the somatostatin analog octreotide. Metformin inhibited QGP-1 cell proliferation in a dose- and time-dependent manner, at concentrations similar to those achievable in treated patients (-31 ± 12%, p 0.05 vs basal at 100 μM). Moreover, metformin decreased pancreatic neuroendocrine tumors (PAN-NETs) cell proliferation (-62 ± 15%, p 0.0001 vs basal at 10 mM), without any additive effect when combined with octreotide. Both octreotide and metformin induced AIP up-regulation. AIP silencing abolished the reduction of mTOR phosphorylation induced by metformin and octreotide. Moreover, metformin decreased HSP70, increased Zac1 and AhR expression; these effects were abolished in AIP silenced QGP-1 cells. In conclusion, metformin acts as an anticancer agent in PAN-NET cells, its activity is mediated by AIP and its interacting proteins. These findings provide a novel insight into the antitumorigenic mechanism of metformin.

Cochineal and indigo in Mesoamerica (1770-1870) - This general history of cochineal and indigo in Mesoamerica points out that these two natural dyes made up a significant proportion of agricultural exports in the 18th and 19th centuries. Despite a few similarities between these two productions (e.g., the use of traditional tools and the absence of economies of scale), differences in organizing work had major consequences on the structure of colonial and postcolonial economies in producer regions. Indians produced cochineal by following their own qualitative criteria, whereas white land-owners and mestizo peasants produced indigo mainly in a quest for profits., Deux colorants naturels cultivés en Méso- Amérique, la cochenille et l'indigo, ont représenté une part considérable des exportations agricoles aux xvme et XIXe siècles. Malgré quelques similitudes entre ces deux cultures, comme l'utilisation d'un outillage traditionnel et l'absence, pour l'un et l'autre produit, d'économie d'échelle, les différences dans le mode d'organisation du travail ont eu des conséquences notables dans la configuration des économies coloniale et postcoloniale des régions concernées. Car la production de la cochenille est assurée par des Indiens et obéit à des critères qualitatifs qui leur sont propres, alors que celle de l'indigo relève de propriétaires blancs et de paysans métis qui cherchent avant tout la rentabilité., Tarantola Giulia. Cochenille et indigo en Méso-Amérique (1770-1870). In: Études rurales, n°151-152, 1999. Autres temps, autres lieux. pp. 43-49.