Published in:

06-09-2022 | Hepatocellular Carcinoma | Original Paper

Dihydroartemisinin inhibited the Warburg effect through YAP1/SLC2A1 pathway in hepatocellular carcinoma

Authors: Qing Peng, Liyuan Hao, Yinglin Guo, Zhiqin Zhang, Jingmin Ji, Yu Xue, Yiwei Liu, Caige Li, Junlan Lu, Xinli Shi

Published in: Journal of Natural Medicines | Issue 1/2023

Abstract

Hepatocellular carcinoma (HCC) was the third most common cause of cancer death. But it has only limited therapeutic options, aggressive nature, and very low overall survival. Dihydroartemisinin (DHA), an anti-malarial drug approved by the Food and Drug Administration (FDA), inhibited cell growth in HCC. The Warburg effect was one of the ten new hallmarks of cancer. Solute carrier family 2 member 1 (SLC2A1) was a crucial carrier for glucose to enter target cells in the Warburg effect. Yes-associated transcriptional regulator 1 (YAP1), an effector molecule of the hippo pathway, played a crucial role in promoting the development of HCC. This study sought to determine the role of DHA in the SLC2A1 mediated Warburg effect in HCC. In this study, DHA inhibited the Warburg effect and SLC2A1 in HepG2215 cells and mice with liver tumors in situ. Meanwhile, DHA inhibited YAP1 expression by inhibiting YAP1 promoter binding protein GA binding protein transcription factor subunit beta 1 (GABPB1) and cAMP responsive element binding protein 1 (CREB1). Further, YAP1 knockdown/knockout reduced the Warburg effect and SLC2A1 expression by shYAP1-HepG2215 cells and Yap1^LKO mice with liver tumors. Taken together, our data indicated that YAP1 knockdown/knockout reduced the SLC2A1 mediated Warburg effect by shYAP1-HepG2215 cells and Yap1^LKO mice with liver tumors induced by DEN/TCPOBOP. DHA, as a potential YAP1 inhibitor, suppressed the SLC2A1 mediated Warburg effect in HCC.

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Title: Dihydroartemisinin inhibited the Warburg effect through YAP1/SLC2A1 pathway in hepatocellular carcinoma
Authors: Qing Peng
Liyuan Hao
Yinglin Guo
Zhiqin Zhang
Jingmin Ji
Yu Xue
Yiwei Liu
Caige Li
Junlan Lu
Xinli Shi
Publication date: 06-09-2022
Publisher: Springer Nature Singapore
Keywords: Hepatocellular Carcinoma
Hepatocellular Carcinoma
Published in: Journal of Natural Medicines / Issue 1/2023
Print ISSN: 1340-3443
Electronic ISSN: 1861-0293
DOI: https://doi.org/10.1007/s11418-022-01641-2

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