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

Cheah, Yew and Nordin, Fariza and Sarip, Rozie and Tee, Thiam and Azimahtol, Hawariah and Sirat, Hasnah M. and Rashid, Badrul and Abdullah, Noor and Ismail, Zakiah (2009) Combined xanthorrhizol-curcumin exhibits synergistic growth inhibitory activity via apoptosis induction in human breast cancer cells MDA-MB-231. Cancer Cell International, 9 (1). p. 1. ISSN 1475-2867

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Official URL: http://dx.doi.org/10.1186/1475-2867-9-1

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 isthe 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.

Item Type:Article
Uncontrolled Keywords:antineoplastic activity, apoptosis, article, breast cancer, cancer cell culture, cancer growth, cancer inhibition, controlled study, cytotoxicity, DNA fragmentation
Subjects:Q Science > QD Chemistry
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions:Biosciences and Bioengineering (Formerly known)
ID Code:13264
Deposited By: Ms Zalinda Shuratman
Deposited On:29 Jul 2011 01:44
Last Modified:29 Jul 2011 01:44

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