title: Betulinic Acid Induces Apoptosis in Differentiated PC12 Cells Via ROS-Mediated Mitochondrial Pathway.
abstract: Betulinic acid (BA), a pentacyclic triterpene of natural origin, has been demonstrated to have varied biologic activities including anti-viral, anti-inflammatory, and anti-malarial effects; it has also been found to induce apoptosis in many types of cancer. However, little is known about the effect of BA on normal cells. In this study, the effects of BA on normal neuronal cell apoptosis and the mechanisms involved were studied using differentiated PC12 cells as a model. Treatment with 50 μM BA for 24 h apparently induced PC12 cell apoptosis. In the early stage of apoptosis, the level of intracellular reactive oxygen species (ROS) increased. Afterwards, the loss of the mitochondrial membrane potential, the release of cytochrome c and the activation of caspase-3 occurred. Treatment with antioxidants could significantly reduce BA-induced PC12 cell apoptosis. In conclusion, we report for the first time that BA induced the mitochondrial apoptotic pathway in differentiated PC12 cells through ROS.
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China.
authors.forename: Xiaocheng
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, Jiangxi Provincial People's Hospital, 92 Aiguo Road, Nanchang, 330006, Jiangxi, China.
authors.forename: Ronglan
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.|Department of Neurosurgery, Huangshan City People's Hospital, 4 Liyuan Road, Huangshan, 245000, Anhui, China.
authors.forename: Kaixin
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.|Department of Neurosurgery, The Second People's Hospital of Huai'an, 62 Huaihainan Road, Huai'an, 223002, Jiangsu, China.
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China. lilixin2@hotmail.com.
authors.forename: Lixin
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D016716:PC12 Cells; D053978:Pentacyclic Triterpenes; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014315:Triterpenes / Q000494:pharmacology*; D000094062:Betulinic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053978:Pentacyclic Triterpenes; D017382:Reactive Oxygen Species; D014315:Triterpenes; D000094062:Betulinic Acid
keywords: Apoptosis; BA; Mitochondrial; PC12 cells; ROS