title: Jolkinolide B induces apoptosis and inhibits tumor growth in mouse melanoma B16F10 cells by altering glycolysis.
abstract: Most cancer cells preferentially rely on glycolysis to produce the energy (adenosine triphosphate, ATP) for growth and proliferation. Emerging evidence demonstrates that the apoptosis in cancer cells could be closely associated with the inhibition of glycolysis. In this study, we have found that jolkinolide B (JB), a bioactive diterpenoid extracted from the root of Euphorbia fischeriana Steud, induced tumor cells apoptosis and decreased the production of ATP and lactic acid in mouse melanoma B16F10 cells. Furthermore, we found that JB downregulated the mRNA expression of glucose transporter genes (Glut1, Glut3 and Glut4) and glycolysis-related kinase genes (Hk2 and Ldha) in B16F10 cells. Moreover, treatment with JB upregulated the mRNA expression of pro-apoptosis genes (Bax), downregulated the mRNA expression of anti-apoptosis genes (Bcl-2, Caspase-3 and Caspase-9), decreased the potential of mitochondrial membrane and increased reactive oxygen species (ROS) levels in B16F10 cells. Finally, intragastric administration of JB suppressed tumor growth and induced tumor apoptosis in mouse xenograft model of murine melanoma B16F10 cells. Taken together, these results suggest that JB could induce apoptosis through the mitochondrial pathway and inhibit tumor growth. The inhibition of glycolysis could play a crucial role in the induction of apoptosis in JB-treated B16F10 cells.
authors: Binzhou Medical University, Yantai 264003, China.
authors: Caixia
authors: C
authors: Gao
authors: Key Laboratory of Xinjiang Endemic Phytomedicine Resources, Pharmacy School, Shihezi University, Ministry of Education, Shihezi 832002, China.
authors: Xinyan
authors: X
authors: Yan
authors: Key Laboratory of Xinjiang Endemic Phytomedicine Resources, Pharmacy School, Shihezi University, Ministry of Education, Shihezi 832002, China.
authors: Bo
authors: B
authors: Wang
authors: Binzhou Medical University, Yantai 264003, China.
authors: Lina
authors: L
authors: Yu
authors: Binzhou Medical University, Yantai 264003, China.
authors: Jichun
authors: J
authors: Han
authors: Binzhou Medical University, Yantai 264003, China.|Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.
authors: Defang
authors: D
authors: Li
authors: Binzhou Medical University, Yantai 264003, China.
authors: Qiusheng
authors: Q
authors: Zheng
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004224:Diterpenes / Q000627:therapeutic use / Q000633:toxicity*; D015536:Down-Regulation / Q000187:drug effects; D028481:Euphorbia / Q000737:chemistry / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000235:genetics / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D006593:Hexokinase / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018517:Plant Roots / Q000737:chemistry / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014184:Transplantation, Homologous; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D004224:Diterpenes; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C495678:Slc2a1 protein, mouse; C495689:Slc2a3 protein, mouse; C495693:Slc2a4 protein, mouse; D051028:bcl-2-Associated X Protein; C057914:jolkinolide B; D000255:Adenosine Triphosphate; D006593:Hexokinase; C000598049:hexokinase 2, mouse; D053148:Caspase 3; D053453:Caspase 9