title: Osthole attenuates doxorubicin-induced apoptosis in PC12 cells through inhibition of mitochondrial dysfunction and ROS production.
abstract: Doxorubicin (DOX) is a potent, broad-spectrum chemotherapeutic drug used for treatment of several types of cancers. Despite its effectiveness, it has a wide range of toxic side effects, many of which most likely result from its inherent prooxidant activity. It has been reported that DOX has toxic effects on normal tissues, including brain tissue. In the current study, we investigated the protective effect of osthole isolated from Prangos ferulacea (L.) Lindl. on oxidative stress and apoptosis induced by DOX in PC12 as a neuronal model cell line. PC12 cells were pretreated with osthole 2 h after treatment with different concentrations of DOX. 24 h later, the cell viability, mitochondrial membrane potential (MMP), the activity of caspase-3, the expression ratio of Bax/Bcl-2, and the generation of intracellular ROS were detected. We found that pretreatment with osthole on PC12 cells significantly reduced the loss of cell viability, the activity of caspase-3, the increase in Bax/Bcl-2 ratio, and the generation of intracellular ROS induced by DOX. Moreover, pretreatment with osthole led to an increase in MMP in PC12 cells. In conclusion, our results indicated that pretreatment with nontoxic concentrations of osthole protected PC12 cells from DOX-mediated apoptosis by inhibition of ROS production.
authors.affiliation: Novel Drug Delivery Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran ; Department of Pharmacognosy and Biotechnology, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran.
authors.forename: Yalda
authors.initials: Y
authors.lastname: Shokoohinia
authors.affiliation: Novel Drug Delivery Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Hosseinzadeh
authors.affiliation: Students Research Committee, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Moieni-Arya
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah 6714869914, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Mostafaie
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah 6714869914, Iran.
authors.forename: Hamid-Reza
authors.initials: HR
authors.lastname: Mohammadi-Motlagh
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D019661:Apiaceae / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects*; D003374:Coumarins / Q000008:administration & dosage* / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D010673:Pheochromocytoma / Q000188:drug therapy* / Q000235:genetics; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D003374:Coumarins; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D004317:Doxorubicin; C046627:osthol