title: Saponin 6 derived from Anemone taipaiensis induces U87 human malignant glioblastoma cell apoptosis via regulation of Fas and Bcl‑2 family proteins.
abstract: Glioblastoma multiforme (GBM) is the most common and aggressive type of brain tumor, and is associated with a poor prognosis. Saponin 6, derived from Anemone taipaiensis, exerts potent cytotoxic effects against the human hepatocellular carcinoma HepG2 cell line and the human promyelocytic leukemia HL‑60 cell line; however, the effects of saponin 6 on glioblastoma remain unknown. The present study aimed to evaluate the effects of saponin 6 on human U87 malignant glioblastoma (U87 MG) cells. The current study revealed that saponin 6 induced U87 MG cell death in a dose‑ and time‑dependent manner, with a half maximal inhibitory concentration (IC50) value of 2.83 µM after treatment for 48 h. However, saponin 6 was needed to be used at a lesser potency in HT‑22 cells, with an IC50 value of 6.24 µM. Cell apoptosis was assessed by flow cytometry using Annexin V‑fluorescein isothiocyanate/propidium iodide double staining. DNA fragmentation and alterations in nuclear morphology were examined by terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling and transmission electron microscopy, respectively. The present study demonstrated that treatment with saponin 6 induced cell apoptosis in U87 MG cells, and resulted in DNA fragmentation and nuclear morphological alterations typical of apoptosis. In addition, flow cytometric analysis revealed that saponin 6 was able to induce cell cycle arrest. The present study also demonstrated that saponin 6‑induced apoptosis of U87 MG cells was attributed to increases in the protein expression levels of Fas, Fas ligand, and cleaved caspase‑3, ‑8 and ‑9, and decreases in the levels of B‑cell lymphoma 2. The current study indicated that saponin 6 may exhibit selective cytotoxicity toward U87 MG cells by activating apoptosis via the extrinsic and intrinsic pathways. Therefore, saponin 6 derived from A. taipaiensis may possess therapeutic potential for the treatment of GBM.
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Chen-Chen
authors.initials: CC
authors.lastname: Ji
authors.affiliation: Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Yi-Yang
authors.initials: YY
authors.lastname: Hu
authors.affiliation: Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Min-Hua
authors.initials: MH
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Qin
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: San-Zhong
authors.initials: SZ
authors.lastname: Li
authors.affiliation: Department of Pharmacy, The 302nd Hospital of Chinese P.L.A., Beijing 100039, P.R. China.
authors.forename: Xiao-Yang
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fei
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Guang
authors.initials: G
authors.lastname: Cheng
mesh_terms: D031883:Anemone / Q000737:chemistry*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology* / Q000633:toxicity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology* / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D012503:Saponins; D019014:fas Receptor