title: 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.affiliation: Department of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Orthopaedics Surgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China.
authors.forename: Honghui
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Oncology, Center Hospital of Shengli Oilfield, Dongying 257034, China.
authors.forename: Jingzhong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Chijiao
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Siqiao
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Guo
authors.affiliation: The Second Department of Surgery, No. 518 Hospital of the PLA, Xi'an 710043, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Lin
authors.affiliation: The Second Department of Surgery, No. 518 Hospital of the PLA, Xi'an 710043, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Haematology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China. Electronic address: liulifmmu@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D019254:Genes, bcl-2; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011134:Polysaccharides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D031993:Sanguisorba / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011134:Polysaccharides; D045304:Cytochromes c; D020169:Caspases
keywords: Apoptosis; Caspase; HL-60 cells; Polysaccharide; Sanguisorbae radix