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Cancer Cell International
Published in: Cancer Cell International 1/2009

Open Access 01-12-2009 | Primary research

Combined xanthorrhizol-curcumin exhibits synergistic growth inhibitory activity via apoptosis induction in human breast cancer cells MDA-MB-231

Authors: Yew Hoong Cheah, Fariza Juliana Nordin, Rozie Sarip, Thiam Tsui Tee, Hawariah Lope Pihie Azimahtol, Hasnah M Sirat, Badrul Amini Abd Rashid, Noor Rain Abdullah, Zakiah Ismail

Published in: Cancer Cell International | Issue 1/2009

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Abstract

Background

It has been suggested that combined effect of natural products may improve the treatment effectiveness in combating proliferation of cancer cells. The present study was undertaken to evaluate the possibility that the combination of xanthorrhizol and curcumin might show synergistic growth inhibitory effect towards MDA-MB-231 human breast cancer cells via apoptosis induction. The effective dose that produced 50% growth inhibition (GI50) was calculated from the log dose-response curve of fixed-combinations of xanthorrhizol and curcumin generated from the sulforhodamine B (SRB) assay. The experimental GI50 value was used to determine the synergistic activity of the combination treatment by isobolographic analysis and combination-index method. Further investigation of mode of cell death induced by the combination treatment was conducted in the present study.

Results

Isobole analysis revealed that substances interaction was synergistic when xanthorrhizol and curcumin were added concurrently to the cultures but merely additive when they were added sequentially. The synergistic combination treatment was then applied to the cultures to investigate the mode of cell death induced by the treatment. Immunofluorescence staining using antibody MitoCapture™ revealed the possibility of altered mitochondrial transmembrane potential, which is one of the hallmark of apoptosis. Hoechst 33258 nuclear staining assay showed the rate of apoptosis of MDA-MB-231 cells to increase in response to the treatment. Apoptotic cell death was further confirmed by DNA fragmentation assay, where internucleosomal excision of DNA was induced upon treatment with xanthorrhizol-curcumin.

Conclusion

This is the first time the combined cytotoxic effect of xanthorrhizol and curcumin on MDA-MB-231 cells has been documented and our findings provide experimental support to the hypothesis that combined xanthorrhizol-curcumin showed synergistic growth inhibitory activity on MDA-MB-231 cells via apoptosis induction.
Appendix
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Metadata
Title
Combined xanthorrhizol-curcumin exhibits synergistic growth inhibitory activity via apoptosis induction in human breast cancer cells MDA-MB-231
Authors
Yew Hoong Cheah
Fariza Juliana Nordin
Rozie Sarip
Thiam Tsui Tee
Hawariah Lope Pihie Azimahtol
Hasnah M Sirat
Badrul Amini Abd Rashid
Noor Rain Abdullah
Zakiah Ismail
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2009
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-9-1

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