Phthalates (PAEs) are considered endocrine-disrupting chemicals (EDCs), a series of compounds able to disrupt the normal regulation of the human endocrine-system. In the present study, we investigated the roles of four PAEs, butyl benzyl phthalate (BBP), dibutyl phthalate (DBP), dimethyl phthalate (DMP), and diethyl phthalate (DEP), in hepatocellular carcinoma (HCC) cells. We define novel roles for the PAEs on the migration of HCC cells via their enhancing of the interaction between the pregnane X receptor (PXR) and E26 transformation specific sequence 1 (ETS-1). Our results indicate that PAEs induced the transcriptional activation of ETS-1 and PXR. PXR activated by PAEs could bind to ETS-1 directly and enhanced the activity of ETS-1, which resulted in the induction of invasion-related ETS-1 target genes. The "LXXLL" motif in the ETS-1C-terminal was essential for the interaction between PXR and ETS-1 induced by PAEs. Treatment of PAEs promoted the nuclear accumulation of ETS-1 or the recruitment of ETS-1, but not in cells expressing ETS-1 with a mutated LXXLL motif in its downstream gene promoter region, or following transfection of PXR siRNA. Treatment with the PXR antagonist ketoconazole almost completely inhibited the effects of PAEs. Moreover, PAEs enhanced the in vitro or in vivo invasion of HCC cells via PXR/ETS-1. Therefore, our results not only contribute to a better understanding of HCC, but also extended the roles of EDCs regulating human malignancies.
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http://dx.doi.org/10.1016/j.phrs.2021.105648 | DOI Listing |
Funct Integr Genomics
January 2025
Institute of Infectious Diseases, Guangdong Province, Guangzhou Eighth People's Hospital, Guangzhou Medical University, 8 Huaying Road, Baiyun District, Guangzhou, 510440, China.
Hepatocellular carcinoma (HCC) remains a malignant and life-threatening tumor with an extremely poor prognosis, posing a significant global health challenge. Despite the continuous emergence of novel therapeutic agents, patients exhibit substantial heterogeneity in their responses to anti-tumor drugs and overall prognosis. The pentose phosphate pathway (PPP) is highly activated in various tumor cells and plays a pivotal role in tumor metabolic reprogramming.
View Article and Find Full Text PDFCancer Sci
January 2025
Hepatobiliary Surgery Center, Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
Immunotherapy has revolutionized cancer treatment, making it a challenge to noninvasively monitor immune infiltration. Metabolic reprogramming in cancers, including hepatocellular carcinoma (HCC), is closely linked to immune status. In this study, we aimed to evaluate the ability of carbon-11 acetate (C-acetate) and fluorine-18 fluorodeoxyglucose (F-FDG) PET/CT findings in predicting overall survival (OS) and immune infiltration in HCC patients.
View Article and Find Full Text PDFAdv Mater
January 2025
Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 200438, P. R. China.
X-ray induced photodynamic therapy (X-PDT) leverages penetrating X-ray to generate singlet oxygen (O) for treating deep-seated tumors. However, conventional X-PDT typically relies on heavy metal inorganic scintillators and organic photosensitizers to produce O, which presents challenges related to toxicity and energy conversion efficiency. In this study, highly biocompatible organic phosphorescent nanoscintillators based on hydrogen-bonded organic frameworks (HOF) are designed and engineered, termed BPT-HOF@PEG, to enhance X-PDT in hepatocellular carcinoma (HCC) treatment.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Lipid Pathobiochemistry Group, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Hepatocellular carcinoma () is one of the leading causes of cancer deaths due to its late diagnosis and restricted therapeutic options. Therefore, the search for appropriate alternatives to commonly applied therapies remains an area of high clinical need. Here we investigated the therapeutic potential of the glucosylceramide synthase (GCS) inhibitor Genz-123346 and the cationic amphiphilic drug aripiprazole on the inhibition of Huh7 and Hepa 1-6 hepatocellular cancer cell and tumor microsphere growth.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Chongqing Key Laboratory of Big Data for Bio Intelligence, Chongqing University of Posts and Telecommunications, Chongqing 400065, China.
Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer with a poor prognosis. During the development of cancer cells, mitochondria influence various cell death patterns by regulating metabolic pathways such as oxidative phosphorylation. However, the relationship between mitochondrial function and cell death patterns in HCC remains unclear.
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