A redox-sensitive signaling pathway mediates pro-angiogenic effect of chlordecone via estrogen receptor activation

Abstract

Our results indicate that an adaptation of the mitochondrial energy metabolism occurs in the chlordecone angiogenic response. Finally, we showed that chlordecone induces endothelial cells angiogenesis by a cross-talk involving NADPH oxidase and mitochondrial Ovia a NO sensitive pathways through activation of ERα. These findings propose that a molecular mechanism may partly explain the epidemiological evidence implicating chlordecone as risk factor carcinogenesis.

In vivo comparison of the proangiogenic properties of chlordecone and three of its dechlorinated derivatives formed by in situ chemical reduction

“…In order to confirm our previous in vitro data (Legeay et al 2017), this study aimed to evaluate the proangiogenic properties of dechlorinated derivatives of CLD compared to CLD in a mouse model of tumor-xenograft and in vitro. In line with the literature, CLD potentiates prostatic tumor growth in vivo (Multigner et al 2010) and this effect was associated with an increased neovascularization (Clere et al 2012;Legeay et al 2017;Alabed Alibrahim et al 2018), confirming the proangiogenic effects of CLD. Prostate cancer is one of the most common cancer diagnosed in men and higher incidence rates have been observed in regions highly exposed to CLD like Caribbean (Center et al 2012).…”

Effect of Chlordecone on the Reproductive Potential of the Cichlid Fish, Pseudetroplus Maculatus (Bloch, 1795)

“…induce the formation of micronucleus and other nuclear abnormalities such as blebbed, notched and lobed nuclei in the erythrocytes of Etroplus maculatus [10]. Chlordecone has been known to activate estrogen receptor-α and promote angiogenesis in human endothelial cells [11], and impaired male reproduction by the alteration in morphology of testes and arrest of sperm maturation in catfish [12]. Important biomarkers of endocrine disruption in fish includes measurement of vitellogenin (VTG) protein, plasma steroid hormones, histopathology of gonads, vitelline envelope proteins (VEPs), morphological features as facial tubercles and nuptial pads, male gender development, detection of enzymes involved in the biosynthesis of sex hormones like cytochrome P450 (CYP)-19, aromatase and C17-lyase and genes involved in estrogen response pathway [13].…”