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

Cheah YH, Nordin FJ, Sarip R, Tee TT, Azimahtol HL, Sirat HM, Rashid BA, Abdullah NR, Ismail Z - Cancer Cell Int. (2009)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Bioassay Unit, Herbal Medicine Research Center, Institute for Medical Research, Jalan Pahang, Kuala Lumpur, Malaysia. yhcheah@gmail.com

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 MitoCapturetrade mark 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.

No MeSH data available.


Related in: MedlinePlus

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Mentions: From our previous study, xanthorrhizol is not able to be separated by normal CC using mixture of solvents with different polarity as other compounds always appeared together as co-eluents. In an effort to purify xanthorrhizol from the final fraction from VCC, subsequent reaction steps (Scheme 1 and Scheme 2) were conducted to facilitate the isolation and purification. Xanthorrhizol was reported as a potential chiral starting material for the synthesis of other sesquiterpenoids [43]. As a result, we started the process of acetylation towards fractions that comprise compound 1 and other co-eluents to produce a lower polarity compound 2 namely, acetyl-xanthorrhizol (Scheme 1).


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

Cheah YH, Nordin FJ, Sarip R, Tee TT, Azimahtol HL, Sirat HM, Rashid BA, Abdullah NR, Ismail Z - Cancer Cell Int. (2009)

(Hydrolysis process)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2630298&req=5

C2: (Hydrolysis process)
Mentions: From our previous study, xanthorrhizol is not able to be separated by normal CC using mixture of solvents with different polarity as other compounds always appeared together as co-eluents. In an effort to purify xanthorrhizol from the final fraction from VCC, subsequent reaction steps (Scheme 1 and Scheme 2) were conducted to facilitate the isolation and purification. Xanthorrhizol was reported as a potential chiral starting material for the synthesis of other sesquiterpenoids [43]. As a result, we started the process of acetylation towards fractions that comprise compound 1 and other co-eluents to produce a lower polarity compound 2 namely, acetyl-xanthorrhizol (Scheme 1).

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Bioassay Unit, Herbal Medicine Research Center, Institute for Medical Research, Jalan Pahang, Kuala Lumpur, Malaysia. yhcheah@gmail.com

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 MitoCapturetrade mark 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.

No MeSH data available.


Related in: MedlinePlus