Background: Phenolic compounds are known for their cytotoxic properties against cancer cells despite
their still unclear general mechanism of action. Herein is reported the evaluation of the cytotoxic effects of
on human osteosarcoma cells of nine phenol derivatives against osteosarcoma cells, and some insights on their
Method and Results: The cytotoxicity was characterized by cell viability, scratch assay, cellular DNA content
measurement, Annexin V apoptosis, mitochondrial calcium and caspase 3/7 assays. The study shows that out of
the nine compounds used in this study, a tetrahydroquinoline derivative, 2-((1,2,3,4-tetrahydroquinolin-1-yl)(4-
methoxyphenyl)methyl) phenol, was found to exhibit strong inhibitory response with IC50 of 50.5 ± 3.8 µM, and
therefore can be a potential chemotherapeutic agent. Further experiments revealed that this compound induces
cell death by apoptosis and also act as a migration inhibitor. Analysis of the mitochondrial calcium following
treatment with the compound on U2OS cells showed a significant reduction in the level of mitochondrial calcium
concentration suggesting a mitochondrial calcium-independent mechanism in triggering apoptosis. Treatment
of HEK293 cells with the compound confirmed the cytotoxic effects of the compound, however, an increase
in the level of mitochondrial calcium was observed. Moreover, the caspase 3/7 mediated cell death was
also observed in both cell types.
Conclusion: Overall, the study suggests that the derivatives of this compound can be used for development of
new therapeutics for osteosarcoma and other cancers.