Chios gum mastic (CGM) is a resin produced from the stem and leaves of Pistiacia lentiscus L var
chia, a plant which grows only on Chios Island in Greece. CGM has been used for many centuries as a dietary
supplement and folk medicine for stomach and duodenal ulcers in many Mediterranean countries and is also known to
induce cell cycle arrest and apoptosis in some cancer cells. This study was undertaken to investigate the alteration of
the cell cycle and induction of apoptosis by CGM treatment on human osteosarcoma (HOS) cells. The viability and the
growth inhi-bition of HOS cells were assessed by the MTT assay and clonogenic assay respectively. The hoechst
staining, TUNEL assay and DNA electrophoresis were conducted to observe the HOS cells undergoing apoptosis. HOS
cells were treated with CGM, and Western blotting, immunocytochemistry, confocal microscopy, FACScan flow
cytometry, mitochon-drial membrane potential change and proteasome activity were conducted. CGM treatment of
HOS cells was found to result in a dose- and time-dependent decrease in cell viability, a dose-dependent inhibition of cell
growth, and apoptotic cell death. Tested HOS cells also showed several lines of apoptotic manifestation and G1 arrest
in cell cycle progres-sion. In summary, this study clearly demonstrated that CGM induces G1 cell cycle arrest via the
modulation of cell cycle-related proteins, and apoptosis via proteasome, mitochondrial and caspase cascades in HOS
cells. Therefore, our data provide the possibility that a natural product, CGM could be considered as a novel
therapeutic strategy for human osteosarcoma.