Anti-osteosarcoma effects and mechanisms of 4-O-amino-phenol-4'-demethylepipodophyllotoxin ether.
The purpose of this study was to investigate the anti-osteosarcoma effects and mechanisms of 4-O-amino-phenol-4'-demethylepipodophyllotoxin ether (ODE), a new derivative of podophyllotoxin. The results showed that ODE inhibited proliferation of K562, OS-9901, CNE, BGC-823 and Tca-8113 cells in a time- and concentration-dependent manner as determined by microculture tetrazolium (MTT) assay. OS-9901 and K562 cells treated with ODE for 24 h showed cell cycle arrest at G(2)/M and a parallel decrease in G(0)/G(1) and S phase as detected by flow cytometry (FCM). Meanwhile, a fraction of cells with hypodiploid DNA content representing apoptosis were detected by FCM. Morphology observation also revealed typical apoptotic features, including shrinkage of cellular and nuclear membranes, condensed heterochromatin around the nuclear periphery and cytoplasmic vacuolation in OS-9901 cells. Under a confocal laser scanning microscope, intracellular Ca2+ and Mg2+ concentrations were greatly increased whereas the pH value, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were markedly reduced in OS-9901 cells after treatment with ODE. Taken together, these results suggest that the anti-osteosarcoma mechanisms of ODE are attributed to apoptosis through increasing intracellular Ca2+ and Mg2+ concentrations, and reducing pH value, MMP and ROS.
Yang
Tuan-Min
TM
Department of Orthopaedics, Affiliated Hospital of Xi'an Medical College, Xi'an, 710077, PR China.
Guo
Shi-Fang
SF
Chen
Chang-Rui
CR
Zhang
Xiao-Yu
XY
Li
Wen-Guang
WG
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy*; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004987:Ethers / Q000008:administration & dosage / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008274:Magnesium / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D012516:Osteosarcoma / Q000188:drug therapy*; D011034:Podophyllotoxin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
C527613:4-O-amino-phenol-4'-demethylepipodophyllotoxin ether; D000970:Antineoplastic Agents; D004987:Ethers; D017382:Reactive Oxygen Species; D008274:Magnesium; D011034:Podophyllotoxin; D002118:Calcium