Anzhelika Karjalainen1, Phuong Doan1, Jerome G Chandraseelan1, Ossi Sandberg1, Olli Yli-Harja1, Nuno R Candeias2, Meenakshisundaram Kandhavelu1.
Abstract
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 mechanism. 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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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 mechanism. 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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Entities:
Keywords:
Phenol-derivatives; anticancer; biological screening; cell death; cytotoxicity; mitochondria
Mesh：
Substances：
Year: 2017
PMID： 28356015 DOI： 10.2174/1871520617666170327142027
Source DB: PubMed Journal: Anticancer Agents Med Chem ISSN： 1871-5206 Impact factor: 2.505