title: 5‑bromo‑3‑(3‑hydroxyprop‑1‑ynyl)‑2H‑pyran‑2‑one induces apoptosis in T24 human bladder cancer cells through mitochondria-dependent signaling pathways.
abstract: The present study was performed to investigate the effect of 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (BHP) on the induction of apoptosis and cell cycle arrest in T24 human bladder carcinoma cells. An MTT assay was used to investigate the inhibition of cell proliferation. Flow cytometry was used to observe alterations in the cell cycle, generation of reactive oxygen species (ROS), alterations in mitochondrial membrane potential (MMP) and induction of apoptosis in the T24 cells following BHP treatment. Western blot analysis was performed for the determination of expression levels of apoptotic proteins, and 4,6‑diamidino‑2‑phenylindole dihydrochloride staining was used to observe apoptosis and DNA damage. The results demonstrated that treatment of the bladder cancer cells with BHP enhanced the activation of caspases and increased the production of ROS. It also caused damage to DNA, reduced MMP, and increased the secretion of endonuclease G and apoptosis‑inducing factor from the mitochondria. The expression levels of cyclin E and cell division cycle 25C were reduced, whereas the expression levels of p21 and phosphorylated p53 were increased in the BHP‑treated cells. In addition, treatment with BHP caused cell cycle arrest at the G0/G1 phase, increased the expression levels of B cell lymphoma‑2 (Bcl‑2)‑associated X protein and poly(ADP‑ribose) polymerase, decreased the expression of Bcl‑2 and ultimately induced apoptosis of the T24 cells. Thus, BHP inhibited the proliferation of bladder cancer cells by inducing cell apoptosis through the mitochondrial pathway.
authors.affiliation: Department of Urological Surgery, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Yu
authors.affiliation: Department of Urological Surgery, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.
authors.forename: Zhong-Ling
authors.initials: ZL
authors.lastname: Dou
authors.affiliation: Department of Urological Surgery, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Jia
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011753:Pyrones / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: C572758:5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one; D000970:Antineoplastic Agents; D011753:Pyrones; D017382:Reactive Oxygen Species