title: Pingyangmycin and Bleomycin Share the Same Cytotoxicity Pathway.
abstract: Pingyangmycin is an anticancer drug known as bleomycin A5 (A5), discovered in the Pingyang County of Zhejiang Province of China. Bleomycin (BLM) is a mixture of mainly two compounds (A2 and B2), which is on the World Health Organization's list of essential medicines. Both BLM and A5 are hydrophilic molecules that depend on transporters or endocytosis receptors to get inside of cells. Once inside, the anticancer activities rely on their abilities to produce DNA breaks, thus leading to cell death. Interestingly, the half maximal inhibitory concentration (IC50) of BLMs in different cancer cell lines varies from nM to μM ranges. Different cellular uptake, DNA repair rate, and/or increased drug detoxification might be some of the reasons; however, the molecules and signaling pathways responsible for these processes are largely unknown. In the current study, we purified the A2 and B2 from the BLM and tested the cytotoxicities and the molecular mechanisms of each individual compound or in combination with six different cell lines, including a Chinese hamster ovary (CHO) cell line defective in glycosaminoglycan biosynthesis. Our data suggested that glycosaminoglycans might be involved in the cellular uptake of BLMs. Moreover, both BLM and A5 shared similar signaling pathways and are involved in cell cycle and apoptosis in different cancer cell lines.
authors.affiliation: School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China. heyanli0219@163.com.|Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University, Qingdao 266003, China. heyanli0219@163.com.
authors.forename: Yanli
authors.initials: Y
authors.lastname: He
authors.affiliation: School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China. yinglanone@yeah.net.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lan
authors.affiliation: School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China. liuyong19900820@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Animal Science and Technology, Northwest A&amp;F University, Xianyang 712100, China. yuhaiboper@163.com.
authors.forename: Haibo
authors.initials: H
authors.lastname: Yu
authors.affiliation: School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China. hzrhan@126.com.
authors.forename: Zhangrun
authors.initials: Z
authors.lastname: Han
authors.affiliation: School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China. ouclixiulian@163.com.
authors.forename: Xiulian
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China. lijuanzhang@ouc.edu.cn.|Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University, Qingdao 266003, China. lijuanzhang@ouc.edu.cn.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001761:Bleomycin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D016466:CHO Cells; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D003412:Cricetulus; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000903:Antibiotics, Antineoplastic; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D001761:Bleomycin; C025703:bleomycetin; D066246:ErbB Receptors
keywords: apoptosis; bleomycin A2; bleomycin A5 or pingyangmycin; bleomycin B2; cell cycle; cytotoxicity