Dihydroartemisinin Regulates Self-Renewal of Human Melanoma-Initiating Cells by Targeting PKM2/LDHA Related Glycolysis
Zhen Li1, Baozhen Zeng2, Baoqing Wang1, Yanbin Xiao3, Xiang Ma3, Zhimin Liu4, Jianqiang Wang5, Suwei Dong51Department of Medical Oncology, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, P. R. China, 2Department of Pathology, Guangdong Provincial People's Hospital/Guangdong Academy of Medical Sciences, Guangzhou, P. R. China, 3Department of orthopaedics, The Third Affiliated Hospital of Kunming Medical University, Kunming, P. R. China, 4Cancer Biotherapy Center, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, P. R. China, 5Department of orthopaedics, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, P. R. China,
Objectives: Melanoma-initiating cells (MICs), a group of cells with stem cell-like self-renewal ability, play a vital role in melanoma progression. They are energized by PKM2/LDHA-related glycolysis. Dihydroartemisin (DHA), a derivative of the antimalarial drug artemisinin, reportedly has a potential role in glycolysis regulation. The aim of this study was to detect the regulation of self-renewal of MICs by DHA through PKM2/LDHA-related glycolysis. Methods: The cell viability of melanoma cells following DHA treatment in vitro was measured by MTS. Cell cycle were detected by Flow cytometry. And DHA treatment in vivo was measured by Nude mouse xenograft assay. MICs self renewal was detected by stem cell related spheres culture and assays. Results: DHA inhibits the proliferation of melanoma cells and blocks the cell cycle process. Importantly, it suppresses the self renewal of MICs. Furthermore, DHA reduces ATP production and downregulate PKM2 and LDHA activities without regulating the expression of the PKM2 and LDHA proteins in melanoma cells. Moreover, DHA covalently binds to the protein skeleton of PKM2 and LDHA through its sesquiterpene lactone structure and downregulates glucose metabolism in melanoma cells. Conclusion: These findings revealed that DHA regulates self-renewal of human MICs by targeting PKM2/LDHA-related glycolysis. Keywords: Dihydroartemisinin, Glycolysis, Melanoma, PKM2, LDHA
Cite This Article
Li Z, Zeng B, Wang B, Xiao Y, Ma X, Liu Z, et al. Dihydroartemisinin Regulates Self-Renewal of Human Melanoma-Initiating Cells by Targeting PKM2/LDHA Related Glycolysis. EJMO. 2024; 8(2): 225-232
Corresponding Author: Suwei Dong