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      • 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,Putri, Dyaningtyas Dewi Pamungkas,Susidarti, Ratna Asmah,Murwanti, Retno,Sardjiman, Sardjiman,Fitriasari, Aditya,Husnaa, Ulfatul,Purnomo, Hari,Kawaichi, Masashi Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

        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.

      • KCI등재

        The improvement of doxorubicin activity on breast cancer cell lines by tangeretin through cell cycle modulation

        Edy Meiyanto,Aditya Fitriasari,Adam Hermawan,Sendy Junedi,Ratna Asmah Susidarti 경희대학교 융합한의과학연구소 2011 Oriental Pharmacy and Experimental Medicine Vol.11 No.3

        Tangeretin, shows cytotoxic effect on COLO 205colon cancer cells. Combination of tangeretin with tamoxifen showed synergistic effect and increased the cancer cell sensitivity towards tamoxifen on T47D cells. However, the combination of tangeretin with chemotherapeutic agent doxorubicin on breast cancer cells have not been explored yet. Therefore, the aim of this research is to examine the improvement of cytotoxic effect of doxorubicin by tangeretin through cell death induction and cell cycle modulation on MCF-7 and T47D cells. The cytotoxic effect of tangeretin, doxorubicin, and their combination on tested cells were carried out by using MTT assay. Cell cycle distribution was determined by flowcytometer FACSCalibur and the flowcytometry data was analyzed using ModFit LT 3.0 program. Cell death assay were done by double staining method using ethydium bromide-acridin orange. Single treatment of tangeretin 5–100 μM did not show cytotoxic effect on MCF-7 and T47D cells. The combination of tangeretin 50 and 100 μM with doxorubicin 200 nM (MCF-7) and 7.5 nM (T47D) increased the cytotoxic effect of doxorubicin on both breast cancer cell lines. This improvement of cytotoxic effect is due to cell death induction and cell cycle modulation. Furthermore,single treatment of tangeretin showed cell death only on T47D cell and caused G1-phase arrest on MCF-7 cell and G2/M-phase arrest on T47D cell. While doxorubicin induced cell accumulation at G2/M phase in both cancer cell lines. However, combination of tangeretin and doxorubicin increased cell death on both cancer cell lines,compared with doxorubicin by itself. The combination also showed G1-phase arrest on MCF-7 cell and increased cell accumulation at G2/M phase on T47D cell. Based on this result, tangeretin is potential to be developed as cochemotherapeutic agent for breast cancer by inducing apoptosis and cell cycle arrest. However, the molecular mechanism need to be explored further.

      • KCI등재

        The improvement of doxorubicin activity on breast cancer cell lines by tangeretin through cell cycle modulation

        Meiyanto, Edy,Fitriasari, Aditya,Hermawan, Adam,Junedi, Sendy,Susidarti, Ratna Asmah 경희한의학연구센터 2011 Oriental Pharmacy and Experimental Medicine Vol.11 No.3

        Tangeretin, shows cytotoxic effect on COLO 205 colon cancer cells. Combination of tangeretin with tamoxifen showed synergistic effect and increased the cancer cell sensitivity towards tamoxifen on T47D cells. However, the combination of tangeretin with chemotherapeutic agent doxorubicin on breast cancer cells have not been explored yet. Therefore, the aim of this research is to examine the improvement of cytotoxic effect of doxorubicin by tangeretin through cell death induction and cell cycle modulation on MCF-7 and T47D cells. The cytotoxic effect of tangeretin, doxorubicin, and their combination on tested cells were carried out by using MTT assay. Cell cycle distribution was determined by flowcytometer FACS-Calibur and the flowcytometry data was analyzed using ModFit LT 3.0 program. Cell death assay were done by double staining method using ethydium bromide-acridin orange. Single treatment of tangeretin 5-100 ${\mu}M$ did not show cytotoxic effect on MCF-7 and T47D cells. The combination of tangeretin 50 and 100 ${\mu}M$ with doxorubicin 200 nM (MCF-7) and 7.5 nM (T47D) increased the cytotoxic effect of doxorubicin on both breast cancer cell lines. This improvement of cytotoxic effect is due to cell death induction and cell cycle modulation. Furthermore, single treatment of tangeretin showed cell death only on T47D cell and caused G1-phase arrest on MCF-7 cell and G2/M-phase arrest on T47D cell. While doxorubicin induced cell accumulation at G2/M phase in both cancer cell lines. However, combination of tangeretin and doxorubicin increased cell death on both cancer cell lines, compared with doxorubicin by itself. The combination also showed G1-phase arrest on MCF-7 cell and increased cell accumulation at G2/M phase on T47D cell. Based on this result, tangeretin is potential to be developed as co-chemotherapeutic agent for breast cancer by inducing apoptosis and cell cycle arrest. However, the molecular mechanism need to be explored further.

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