The antitumor activities of curcumin and its isoxazole analogue are not affected by multiple gene expression changes in an MDR model of the MCF-7 brest cancer cell line: Analysis of the possible molecular basis.

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Abstract

We examined the effects of curcumin and of its isoxazole analogue MR 39 in the MCF-7 breast cancer cell line and in its multidrug-resistant (MDR) variant MCF-7R. In comparison with MCF-7, MCF-7R lacks estrogen receptor alpha (ERalpha) and overexpressess P-glycoprotein (P-gp), different IAPs (inhibitory of apoptosis proteins) and COX-2. Through analyses of the effects on cell proliferation, cycling and death, we have observed that the antitumor activity of curcumin and of the more potent (approximately two-fold) MR 39 is at least equal in the MDR cell line compared to the parental MCF-7. Similar results were observed also in an MDR variant of HL-60 leukemia. RT-PCR evaluations performed in MCF-7 and MCF-7R showed that curcumin or MR 39 produced early modifications in the amounts of relevant gene transcripts, which, however, were mostly diverse (i.e. represented by decreases in IAPs and COX-2 in MCF-7R versus reductions in Bcl-2 and Bcl-XL as well as increases in the Bcl-XS/Bcl-XL ratio in MCF-7) in the two cell lines. These results could not be explained by an involvement of NF-kappaB (p65 subunit) or STAT3, since the low nuclear levels of these transcription factors present in MCF-7 were only slightly, though significantly, elevated in MCF-7R; moreover, curcumin or MR 39 caused minor changes in NF-kappaB or STAT3 activation. Overall, these data underline that curcumin or MR 39 antitumor activities are not hampered by P-gp expression or lack of ERalpha in breast cancer cells. Remarkably, the agents appeared to modify their molecular effects according to the diverse gene expression patterns existing in the MDR and in the parental MCF-7. Clearly, the structure and properties of curcumin can form the basis for the development of antitumor compounds that are more effective against both chemosensitive and MDR cells.
Lingua originaleEnglish
pagine (da-a)329-335
Numero di pagine7
RivistaInternational Journal of Molecular Medicine
Volume20
Stato di pubblicazionePublished - 2007

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Isoxazoles
Curcumin
Gene Expression
Cell Line
Neoplasms
Estrogen Receptor alpha
NF-kappa B
P-Glycoprotein
Apoptosis
Breast Neoplasms
Leukemia
Proteins
Cell Death
Transcription Factors
Cell Proliferation
Polymerase Chain Reaction
Genes

All Science Journal Classification (ASJC) codes

  • Genetics

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@article{658c30a75f7c47d9a41cb66886e3a2fc,
title = "The antitumor activities of curcumin and its isoxazole analogue are not affected by multiple gene expression changes in an MDR model of the MCF-7 brest cancer cell line: Analysis of the possible molecular basis.",
abstract = "We examined the effects of curcumin and of its isoxazole analogue MR 39 in the MCF-7 breast cancer cell line and in its multidrug-resistant (MDR) variant MCF-7R. In comparison with MCF-7, MCF-7R lacks estrogen receptor alpha (ERalpha) and overexpressess P-glycoprotein (P-gp), different IAPs (inhibitory of apoptosis proteins) and COX-2. Through analyses of the effects on cell proliferation, cycling and death, we have observed that the antitumor activity of curcumin and of the more potent (approximately two-fold) MR 39 is at least equal in the MDR cell line compared to the parental MCF-7. Similar results were observed also in an MDR variant of HL-60 leukemia. RT-PCR evaluations performed in MCF-7 and MCF-7R showed that curcumin or MR 39 produced early modifications in the amounts of relevant gene transcripts, which, however, were mostly diverse (i.e. represented by decreases in IAPs and COX-2 in MCF-7R versus reductions in Bcl-2 and Bcl-XL as well as increases in the Bcl-XS/Bcl-XL ratio in MCF-7) in the two cell lines. These results could not be explained by an involvement of NF-kappaB (p65 subunit) or STAT3, since the low nuclear levels of these transcription factors present in MCF-7 were only slightly, though significantly, elevated in MCF-7R; moreover, curcumin or MR 39 caused minor changes in NF-kappaB or STAT3 activation. Overall, these data underline that curcumin or MR 39 antitumor activities are not hampered by P-gp expression or lack of ERalpha in breast cancer cells. Remarkably, the agents appeared to modify their molecular effects according to the diverse gene expression patterns existing in the MDR and in the parental MCF-7. Clearly, the structure and properties of curcumin can form the basis for the development of antitumor compounds that are more effective against both chemosensitive and MDR cells.",
keywords = "curcumin, isoxazole derivative, multidrug resistance, P-glycoprotein, estrogen receptor, inhibitory of apoptosis proteins",
author = "Natale D'Alessandro and Manuela Labbozzetta and {Notarbartolo Di Villarosa}, Monica and Paola Poma and Alessandra Alaimo and Valeria Carina and Annamaria Maurici",
year = "2007",
language = "English",
volume = "20",
pages = "329--335",
journal = "International Journal of Molecular Medicine",
issn = "1107-3756",
publisher = "Spandidos Publications",

}

TY - JOUR

T1 - The antitumor activities of curcumin and its isoxazole analogue are not affected by multiple gene expression changes in an MDR model of the MCF-7 brest cancer cell line: Analysis of the possible molecular basis.

AU - D'Alessandro, Natale

AU - Labbozzetta, Manuela

AU - Notarbartolo Di Villarosa, Monica

AU - Poma, Paola

AU - Alaimo, Alessandra

AU - Carina, Valeria

AU - Maurici, Annamaria

PY - 2007

Y1 - 2007

N2 - We examined the effects of curcumin and of its isoxazole analogue MR 39 in the MCF-7 breast cancer cell line and in its multidrug-resistant (MDR) variant MCF-7R. In comparison with MCF-7, MCF-7R lacks estrogen receptor alpha (ERalpha) and overexpressess P-glycoprotein (P-gp), different IAPs (inhibitory of apoptosis proteins) and COX-2. Through analyses of the effects on cell proliferation, cycling and death, we have observed that the antitumor activity of curcumin and of the more potent (approximately two-fold) MR 39 is at least equal in the MDR cell line compared to the parental MCF-7. Similar results were observed also in an MDR variant of HL-60 leukemia. RT-PCR evaluations performed in MCF-7 and MCF-7R showed that curcumin or MR 39 produced early modifications in the amounts of relevant gene transcripts, which, however, were mostly diverse (i.e. represented by decreases in IAPs and COX-2 in MCF-7R versus reductions in Bcl-2 and Bcl-XL as well as increases in the Bcl-XS/Bcl-XL ratio in MCF-7) in the two cell lines. These results could not be explained by an involvement of NF-kappaB (p65 subunit) or STAT3, since the low nuclear levels of these transcription factors present in MCF-7 were only slightly, though significantly, elevated in MCF-7R; moreover, curcumin or MR 39 caused minor changes in NF-kappaB or STAT3 activation. Overall, these data underline that curcumin or MR 39 antitumor activities are not hampered by P-gp expression or lack of ERalpha in breast cancer cells. Remarkably, the agents appeared to modify their molecular effects according to the diverse gene expression patterns existing in the MDR and in the parental MCF-7. Clearly, the structure and properties of curcumin can form the basis for the development of antitumor compounds that are more effective against both chemosensitive and MDR cells.

AB - We examined the effects of curcumin and of its isoxazole analogue MR 39 in the MCF-7 breast cancer cell line and in its multidrug-resistant (MDR) variant MCF-7R. In comparison with MCF-7, MCF-7R lacks estrogen receptor alpha (ERalpha) and overexpressess P-glycoprotein (P-gp), different IAPs (inhibitory of apoptosis proteins) and COX-2. Through analyses of the effects on cell proliferation, cycling and death, we have observed that the antitumor activity of curcumin and of the more potent (approximately two-fold) MR 39 is at least equal in the MDR cell line compared to the parental MCF-7. Similar results were observed also in an MDR variant of HL-60 leukemia. RT-PCR evaluations performed in MCF-7 and MCF-7R showed that curcumin or MR 39 produced early modifications in the amounts of relevant gene transcripts, which, however, were mostly diverse (i.e. represented by decreases in IAPs and COX-2 in MCF-7R versus reductions in Bcl-2 and Bcl-XL as well as increases in the Bcl-XS/Bcl-XL ratio in MCF-7) in the two cell lines. These results could not be explained by an involvement of NF-kappaB (p65 subunit) or STAT3, since the low nuclear levels of these transcription factors present in MCF-7 were only slightly, though significantly, elevated in MCF-7R; moreover, curcumin or MR 39 caused minor changes in NF-kappaB or STAT3 activation. Overall, these data underline that curcumin or MR 39 antitumor activities are not hampered by P-gp expression or lack of ERalpha in breast cancer cells. Remarkably, the agents appeared to modify their molecular effects according to the diverse gene expression patterns existing in the MDR and in the parental MCF-7. Clearly, the structure and properties of curcumin can form the basis for the development of antitumor compounds that are more effective against both chemosensitive and MDR cells.

KW - curcumin, isoxazole derivative, multidrug resistance, P-glycoprotein, estrogen receptor, inhibitory of apoptosis proteins

UR - http://hdl.handle.net/10447/19742

M3 - Article

VL - 20

SP - 329

EP - 335

JO - International Journal of Molecular Medicine

JF - International Journal of Molecular Medicine

SN - 1107-3756

ER -