Xiao Jin Wan, a traditional Chinese herbal formula, inhibits proliferation             via arresting cell cycle progression at the G2/M phase and promoting apoptosis             via activating the mitochondrial‑dependent pathway in U-2OS human osteosarcoma             cells.
Xiao Jin Wan (XJW) is a well-known traditional Chinese folk-medicine, which is commonly used for the treatment of various types of diseases including cancers. However, the mechanism of the anticancer activity of XJW against U-2OS human osteosarcoma cells, have not yet been reported. In the present study, we investigated the cellular effects of the XJW on the U-2OS human osteosarcoma cell line. Our results showed that XJW induced cell morphological changes, reduced cell viability in a dose- and time-dependent manner and arrested in the G2/M phase of the cell cycle suggesting that XJW inhibited the proliferation of U-2OS cells. Hoechst 33258 staining and Annexin V/propidium iodide double staining exhibited the typical nuclear features of apoptosis and increased the proportion of apoptotic Annexin V-positive cells in a dose-dependent manner, respectively. In addition, XJW treatment caused loss of plasma membrane asymmetry, collapse of mitochondrial membrane potential, activation of caspase-9 and caspase-3, and increase of the ratio of pro-apoptotic Bax to anti-apoptotic Bcl-2. Taken together, the results indicate that the U-2OS cell growth inhibitory activity of XJW was due to cell cycle arrested and mitochondrial-mediated apoptosis, which may partly explain the anticancer activity of Xiao Jin Wan.
Academy of Integrative Medicine, Fujian University of Traditional                     Chinese Medicine, Fuzhou 350122, P.R. China.
Guangwen
G
Wu
Jianfeng
J
Chu
Zhengrong
Z
Huang
Jinxia
J
Ye
Panyu
P
Chen
Chunsong
C
Zheng
Xihai
X
Li
Xianxiang
X
Liu
Mingxia
M
Wu
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004789:Enzyme Activation; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism; D008517:Phytotherapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D004365:Drugs, Chinese Herbal; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D053453:Caspase 9