The widespread use of phthalates as plasticizers particularly in polyvinylchloride (PVC) products has raised public health concerns recently due to their adverse health effects, including cancer. Although sufficient evidences of animal investigations suggested the association of phthalates exposure and hepatoma, the mechanisms remain unclear. This study of the effects of phthalates on hepatoma cells progression through AhR shows that butyl benzyl phthalate (BBP) stimulates AhR at the cell surface, interacts with G protein, and triggers the downstream signaling cascade. The experimental results suggest that BBP activates AhR through a nongenomic action, involving G protein signaling other than the classical genomic AhR action. Further experiments have shown that BBP induces both in vitro and in vivo angiogenesis through the AhR/ERK/VEGF pathway. Moreover, the study also reveals that BBP treatment promotes migration, invasion in vitro and metastasis in vivo via AhR/Gβ/PI3K/Akt/NF-κB pathway. Collectively, the findings suggest a novel nongenomic AhR mechanism of phthalates that contributes to tumor progression in hepatoma. The finding will be useful when developing approaches for preventing and treating liver cancer.

Citation Format: Eing-Mei Tsai, Cheng-Fang Tsai. Butyl benzyl phthalate induces metastasis and angiogenesis of hepatocellular carcinoma through a nongenomic AhR/G protein signaling. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A41.

©2012 American Association for Cancer Research.
2012