A polysaccharide from Sanguisorbae radix induces caspase-dependent apoptosis in human leukemia HL-60 cells.

Abstract

One polysaccharide (SRP) was purified from Sanguisorbae radix by DEAE-cellulose-52 anion-exchange and Sephacryl S-400 gel filtration chromatography. The aim of this study was to evaluate the anticancer efficacy of SRP on human leukemia HL-60 cells in vitro and unveil the underlying mechanisms. Our results showed that SRP was able to suppress the proliferation of HL-60 cells in a dose-dependent manner by the mechanism involved in the induction of apoptosis. The increase in SRP-induced apoptosis was correlated with a rapid and sustained loss of mitochondrial transmembrane potential (ΔΨm) and a release of cytochrome c from the mitochondria into the cytosol. Furthermore, Western blot and RT-PCR analysis revealed that the protein and mRNA levels of antiapoptotic Bcl-2 were downregulated, whereas those of pro-apoptotic Bax were upregulated. Besides, caspase-9 and caspase-3 were activated, while caspase-8 was intact. Additionally, the apoptotic cells by SRP were significantly inhibited by a caspase-3 inhibitor (z-DEVD-fmk) or a caspase-9 inhibitor (Z-LETD-FMK), demonstrating the important role of caspase-9 and -3 in the process. Taken together, these findings provided evidence that SRP induced the apoptosis of HL-60 cells through an intrinsic mitochondria-mediated signaling pathway and SRP may be a promising chemotherapeutic agent for treatment of leukemia.

• Authors: Zhigang Wu, Honghui Sun, Jingzhong Li, Chijiao Ma, Siqiao Zhao, Zheng Guo, Yao Lin, Yaping Lin, Li Liu
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 70 Pg. 615-20 (Sep 2014) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 25036608 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Polysaccharides
• Cytochromes c
• Caspases

Topics

• Antineoplastic Agents, Phytogenic (chemistry, pharmacology)
• Apoptosis (drug effects, genetics)
• Caspases (metabolism)
• Cell Proliferation (drug effects)
• Cytochromes c (metabolism)
• Enzyme Activation (drug effects)
• Genes, bcl-2
• HL-60 Cells
• Humans
• Leukemia (genetics, metabolism)
• Membrane Potential, Mitochondrial (drug effects)
• Polysaccharides (chemistry, isolation & purification, pharmacology)
• Sanguisorba (chemistry)