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Molecules 2016, 21(7), 862; doi:10.3390/molecules21070862

Pingyangmycin and Bleomycin Share the Same Cytotoxicity Pathway

1,2,†
,
1,†
,
1
,
3
,
1
,
1
and
1,2,*
1
School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China
2
Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University, Qingdao 266003, China
3
College of Animal Science and Technology, Northwest A&F University, Xianyang 712100, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 11 May 2016 / Revised: 13 June 2016 / Accepted: 15 June 2016 / Published: 30 June 2016
View Full-Text   |   Download PDF [3041 KB, uploaded 30 June 2016]   |  

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. View Full-Text
Keywords: bleomycin A2; bleomycin B2; bleomycin A5 or pingyangmycin; cytotoxicity; cell cycle; apoptosis bleomycin A2; bleomycin B2; bleomycin A5 or pingyangmycin; cytotoxicity; cell cycle; apoptosis
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MDPI and ACS Style

He, Y.; Lan, Y.; Liu, Y.; Yu, H.; Han, Z.; Li, X.; Zhang, L. Pingyangmycin and Bleomycin Share the Same Cytotoxicity Pathway. Molecules 2016, 21, 862.

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