Epigallocatechin-3-Gallate Decreases Hypoxia-Inducible Factor-1 in Pancreatic Cancer Cells.

Hypoxia-inducible factor-1 (HIF-1) is an [Formula: see text]/[Formula: see text] heterodimeric transcription factor. In normal mammalian cells, HIF-1[Formula: see text] is hydroxylated and degraded upon biosynthesis. However, HIF-1[Formula: see text] is frequently expressed in cancer and adds to cancer malignancy. In this study, we investigated whether green tea-derived epigallocatechin-3-gallate (EGCG) decreased HIF-1[Formula: see text] in pancreatic cancer cells. After MiaPaCa-2 and PANC-1 pancreatic cancer cells were exposed to EGCG in vitro, we performed a Western blot to determine native and hydroxylated HIF-1[Formula: see text], which was in turn used to assess HIF-1[Formula: see text] production. In order to assess HIF-1[Formula: see text] stability, we determined the HIF-1[Formula: see text] after MiaPaCa-2 and PANC-1 cells were switched from hypoxia to normoxia. We found that EGCG decreased both production and stability of HIF-1[Formula: see text]. Further, the EGCG-induced decrease in HIF-1[Formula: see text] reduced intracellular glucose transporter-1 and glycolytic enzymes and attenuated glycolysis, ATP production, and cell growth. Because EGCG is known to inhibit cancer-induced insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R), we created three MiaPaCa-2 sublines whose IR, IGF1R, and HIF-1[Formula: see text] were decreased using RNA interference. From wild-type MiaPaCa-2 cells and these sublines, we found evidence that suggested that the EGCG-induced inhibition of HIF-1[Formula: see text] was both dependent on and independent of IR and IGF1R. In vivo, we transplanted wild-type MiaPaCa-2 cells in athymic mice and treated the mice with EGCG or vehicle. When the resulting tumors were analyzed, we found that EGCG decreased tumor-induced HIF-1[Formula: see text] and tumor growth. In conclusion, EGCG decreased HIF-1[Formula: see text] in pancreatic cancer cells and sabotaged the cells. The anticancer effects of EGCG were both dependent on and independent of IR and IGF1R.

Citation

Lijuan Hu, Xiaoqing Xu, Xijuan Chen, Shuai Qiu, Qiuju Li, Dapeng Zhang, Feng Wang. Epigallocatechin-3-Gallate Decreases Hypoxia-Inducible Factor-1 in Pancreatic Cancer Cells. The American journal of Chinese medicine. 2023;51(3):761-777

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PMID: 36867109

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