title: Wogonoside induces cell cycle arrest and mitochondrial mediated apoptosis by modulation of Bcl-2 and Bax in osteosarcoma cancer cells.
abstract: Osteosarcoma (OS) is the most common bone cancer with a great tendency for local invasion and distant metastasis. Restricted by the severe toxicity of conventional drugs, the therapeutic challenge of osteosarcoma still remains unconquered. The objective of the present research work was to investigate the antiproliferative activity of wogonoside against human osteosarcoma (SaOS-2) cell line. Cell viability after wogonoside treatment was evaluated by MTT assay. Phase contrast microscopy was used to evaluate the change in cell morphology following drug treatment. The effect of wogonoside on cell cycle phase distribution and mitochondrial membrane potential was investigated by flow cytometry using propidium iodide (PI) and rhodamine-123 DNA-binding fluorescent dyes respectively. Western blotting was used to evaluate the effect of wogonoside on cell cycle-related proteins as well as on the expression levels of Bcl-2, Bax, cytosolic and mitochondrial cytochrome c and apoptotic protease activating factor-1 (Apaf-1). Wogonoside induced a dose-dependent as well as time-dependent growth inhibitory effects on cell proliferation of SaOS-2 cancer cells. Wogonoside induced G2/M cell cycle arrest as well as loss in mitochondrial membrane potential in these cells. Within 48 h of incubation, approximately 4.36%, 6.72%, 11.54%, 21.88% and 15.54% of the cells underwent early apoptosis after treatment with 0, 5, 10, 25 and 75 μM of wogonoside respectively. Wogonoside led to reduced Bcl-2 expression and increased Bax expression, while as it led to s decrease in the levels of mitochondrial cytochrome c and an increase in cytosolic fraction and expressions of cytosolic apoptotic protease activating factor-1 (Apaf-1).
authors.affiliation: Department of Orthopedics, China-Japan Union Hospital of Jilin University Changchun 130033, Jilin, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, China-Japan Union Hospital of Jilin University Changchun 130033, Jilin, China.
authors.forename: Ruo-Feng
authors.initials: RF
authors.lastname: Yin
authors.affiliation: Department of Orthopedics, Daqing Oilfields general hospital Daqing 163000, Heilongjiang, China.
authors.forename: Jia-Song
authors.initials: JS
authors.lastname: Teng
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; D005434:Flow Cytometry; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008858:Microscopy, Phase-Contrast; D012516:Osteosarcoma / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D044950:Flavanones; D005960:Glucosides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C473995:wogonoside
keywords: Osteosarcoma; apoptosis; cell cycle; mitochondria; wogonoside