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http://dx.doi.org/10.7314/APJCP.2014.15.1.179

Curcumin and its Analogues (PGV-0 and PGV-1) Enhance Sensitivity of Resistant MCF-7 Cells to Doxorubicin through Inhibition of HER2 and NF-kB Activation  

Meiyanto, Edy (Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada)
Putri, Dyaningtyas Dewi Pamungkas (Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada)
Susidarti, Ratna Asmah (Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada)
Murwanti, Retno (Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada)
Sardjiman, Sardjiman (Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada)
Fitriasari, Aditya (Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada)
Husnaa, Ulfatul (Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada)
Purnomo, Hari (Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada)
Kawaichi, Masashi (Lab Of Gene Function, School of Biosciences, Nara Institute of Science and Technology)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.1, 2014 , pp. 179-184 More about this Journal
Abstract
Chemoresistance of breast cancer to doxorubicin is mediated mainly through activation of NF-kB and over expression of HER2. Curcumin and its analogues (PGV-0 and PGV-1) exert cytotoxic effects on T47D breast cancer cells. Suppression of NF-kB activation is suggested to contribute to this activity. The present study aimed to explore the effects of curcumin, PGV-0, and PGV-1 singly and in combination with doxorubicin on MCF-7/Dox cells featuring over-expression of HER2. In MTT assays, curcumin, PGV-0, and PGV-1 showed cytotoxicity effects against MCF-7/Dox with IC50 values of $80{\mu}M$, $21{\mu}M$, and $82{\mu}M$ respectively. These compounds increased MCF-7/Dox sensitivity to doxorubicin. Cell cycle distribution analysis exhibited that the combination of curcumin and its analogues with Dox increased sub G-1 cell populations. Curcumin and PGV-1 but not PGV-0 decreased localization of p65 into the nucleus induced by Dox, indicating that activation of NF-kB was inhibited. Molecular docking of curcumin, PGV-0, and PGV-1 demonstrated high affinity to HER2 at ATP binding site. This interaction were directly comparable with those of ATP and lapatinib. These findings suggested that curcumin, PGV-0 and PGV-1 enhance the Dox cytotoxicity to MCF-7 cells through inhibition of HER2 activity and NF-kB activation.
Keywords
Curcumin and its analogues; HER2; MCF-7/Dox cells; NF-kB;
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Times Cited By KSCI : 1  (Citation Analysis)
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