2. Academic Validation
  3. Pingyangmycin and Bleomycin Share the Same Cytotoxicity Pathway

Pingyangmycin and Bleomycin Share the Same Cytotoxicity Pathway

  • Molecules. 2016 Jun 30;21(7):862. doi: 10.3390/molecules21070862.
Yanli He 1 2,  Ying Lan 3,  Yong Liu 4,  Haibo Yu 5,  Zhangrun Han 6,  Xiulian Li 7,  Lijuan Zhang 8 9
Affiliations

Affiliations

  • 1 School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China. heyanli0219@163.com.
  • 2 Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University, Qingdao 266003, China. heyanli0219@163.com.
  • 3 School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China. yinglanone@yeah.net.
  • 4 School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China. liuyong19900820@163.com.
  • 5 College of Animal Science and Technology, Northwest A&F University, Xianyang 712100, China. yuhaiboper@163.com.
  • 6 School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China. hzrhan@126.com.
  • 7 School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China. ouclixiulian@163.com.
  • 8 School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China. lijuanzhang@ouc.edu.cn.
  • 9 Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University, Qingdao 266003, China. lijuanzhang@ouc.edu.cn.
PMID: 27376254 DOI: 10.3390/molecules21070862
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.

Keywords

apoptosis; bleomycin A2; bleomycin A5 or pingyangmycin; bleomycin B2; cell cycle; cytotoxicity.

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