The Experts below are selected from a list of 130428 Experts worldwide ranked by ideXlab platform
Yoshihiko Ueda - One of the best experts on this subject based on the ideXlab platform.
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the pi3k akt inhibitor LY294002 reverses bcrp mediated drug resistance without affecting bcrp translocation
Oncology Reports, 2012Co-Authors: Yasuo Imai, Mayumi Yoshimori, Kazunori Fukuda, Hidetsugu Yamagishi, Yoshihiko UedaAbstract:Cellular responses toward cytotoxic drugs are influenced by crosstalk between oncogenic signals and resistance mechanisms. Inhibition of the PI3K/Akt pathway is effective in sensitizing cancer cells of various organs, although the mechanisms largely remain to be elucidated. Breast cancer resistance protein (BCRP)/ABCG2, a drug efflux pump, confers resistance to multiple anticancer agents such as SN-38 and topotecan. Previous studies reported that inhibition of the PI3K/Akt pathway, by gene knockout or PI3K inhibitors, modulated BCRP-mediated drug transport via BCRP translocation in hematopoietic stem cells, renal polarized cells and glioma stem-like cells of mammals. In this study, we assessed the effects of PI3K inhibitors, LY294002 and wortmannin, on BCRP-mediated anticancer drug resistance of human cancer MCF-7 and A431 cells. LY294002, but not wortmannin, reversed the BCRP-mediated SN-38 and topotecan resistance. LY294002 treatment did not affect total or cell surface BCRP levels as determined by western blotting and flow cytometry but blocked BCRP-mediated topotecan efflux in a dose-dependent manner. Immunohistochemical analyses also demonstrated unchanged cellular BCRP distribution. BCRP overexpression in MCF-7 and A431 cells did not confer LY294002 resistance, suggesting that LY294002 is not a transported substrate of BCRP. LY294002 is a derivative of quercetin, a member of flavonoids. Taken together, these results suggest that LY294002 inhibits BCRP-mediated drug transport not by BCRP translocation through the PI3K/Akt signal but putatively as a competitive inhibitor in a major subset of cancer cells. Due to its dual effects, LY294002 could be a lead compound for developing more effective and tolerable reagents for cancer treatment.
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Abstract 5612: The PI3K/Akt inhibitor LY294002 reverses BCRP/ABCG2-mediated drug resistance without BCRP translocation
Experimental and Molecular Therapeutics, 2012Co-Authors: Yasuo Imai, Hidetsugu Yamagishi, Yoshihiko UedaAbstract:Cellular responses toward cytotoxic drugs are influenced by cross-talk between oncogenic signals and resistance mechanisms. Inhibition of the PI3K/Akt pathway is effective in sensitizing cancer cells of various organs, although the mechanisms have largely remained to be elucidated. Breast cancer resistance protein (BCRP)/ABCG2, a drug efflux pump, confers resistance to multiple anticancer agents such as SN-38 and topotecan. Previous studies reported that inhibition of the PI3K/Akt pathway, by gene knockout or PI3K inhibitors, modulated BCRP-mediated drug transport via BCRP translocation in hematopoietic stem cells, renal polarized cells, and glioma stem-like cells of mammals. In this paper, we tested reversing effects of PI3K inhibitors, LY294002 and wortmannin, on BCRP-mediated anticancer drug resistance of human cancer MCF-7 and A431 cells. LY294002 definitely reversed BCRP-mediated SN-38 and topotecan resistances but wortmannin did not. LY294002 treatment affected neither total nor cell surface BCRP levels by western blotting and flow cytometry but blocked BCRP-mediated topotecan efflux in a dose-dependent manner. Immunohistochemical analyses also demonstrated unchanged cellular BCRP distribution. BCRP overexpression in MCF-7 and A431 cells did not confer LY294002 resistance, suggesting that LY294002 would not be a transported substrate of BCRP. LY294002 is a derivative of quercetin, a member of flavonoid. Taken together, these results suggest that LY294002 inhibits BCRP-mediated drug transport not by BCRP translocation through the PI3K/Akt signal but putatively as a competitive inhibitor in a major subset of cancer cells. Due to its dual effects, LY294002 could be a lead compound for developing more effective and tolerable reagents for cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5612. doi:1538-7445.AM2012-5612
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abstract 5612 the pi3k akt inhibitor LY294002 reverses bcrp abcg2 mediated drug resistance without bcrp translocation
Cancer Research, 2012Co-Authors: Yasuo Imai, Hidetsugu Yamagishi, Yoshihiko UedaAbstract:Cellular responses toward cytotoxic drugs are influenced by cross-talk between oncogenic signals and resistance mechanisms. Inhibition of the PI3K/Akt pathway is effective in sensitizing cancer cells of various organs, although the mechanisms have largely remained to be elucidated. Breast cancer resistance protein (BCRP)/ABCG2, a drug efflux pump, confers resistance to multiple anticancer agents such as SN-38 and topotecan. Previous studies reported that inhibition of the PI3K/Akt pathway, by gene knockout or PI3K inhibitors, modulated BCRP-mediated drug transport via BCRP translocation in hematopoietic stem cells, renal polarized cells, and glioma stem-like cells of mammals. In this paper, we tested reversing effects of PI3K inhibitors, LY294002 and wortmannin, on BCRP-mediated anticancer drug resistance of human cancer MCF-7 and A431 cells. LY294002 definitely reversed BCRP-mediated SN-38 and topotecan resistances but wortmannin did not. LY294002 treatment affected neither total nor cell surface BCRP levels by western blotting and flow cytometry but blocked BCRP-mediated topotecan efflux in a dose-dependent manner. Immunohistochemical analyses also demonstrated unchanged cellular BCRP distribution. BCRP overexpression in MCF-7 and A431 cells did not confer LY294002 resistance, suggesting that LY294002 would not be a transported substrate of BCRP. LY294002 is a derivative of quercetin, a member of flavonoid. Taken together, these results suggest that LY294002 inhibits BCRP-mediated drug transport not by BCRP translocation through the PI3K/Akt signal but putatively as a competitive inhibitor in a major subset of cancer cells. Due to its dual effects, LY294002 could be a lead compound for developing more effective and tolerable reagents for cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5612. doi:1538-7445.AM2012-5612
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The PI3K/Akt inhibitor LY294002 reverses BCRP-mediated drug resistance without affecting BCRP translocation.
Oncology reports, 2012Co-Authors: Yasuo Imai, Mayumi Yoshimori, Kazunori Fukuda, Hidetsugu Yamagishi, Yoshihiko UedaAbstract:Cellular responses toward cytotoxic drugs are influenced by crosstalk between oncogenic signals and resistance mechanisms. Inhibition of the PI3K/Akt pathway is effective in sensitizing cancer cells of various organs, although the mechanisms largely remain to be elucidated. Breast cancer resistance protein (BCRP)/ABCG2, a drug efflux pump, confers resistance to multiple anticancer agents such as SN-38 and topotecan. Previous studies reported that inhibition of the PI3K/Akt pathway, by gene knockout or PI3K inhibitors, modulated BCRP-mediated drug transport via BCRP translocation in hematopoietic stem cells, renal polarized cells and glioma stem-like cells of mammals. In this study, we assessed the effects of PI3K inhibitors, LY294002 and wortmannin, on BCRP-mediated anticancer drug resistance of human cancer MCF-7 and A431 cells. LY294002, but not wortmannin, reversed the BCRP-mediated SN-38 and topotecan resistance. LY294002 treatment did not affect total or cell surface BCRP levels as determined by western blotting and flow cytometry but blocked BCRP-mediated topotecan efflux in a dose-dependent manner. Immunohistochemical analyses also demonstrated unchanged cellular BCRP distribution. BCRP overexpression in MCF-7 and A431 cells did not confer LY294002 resistance, suggesting that LY294002 is not a transported substrate of BCRP. LY294002 is a derivative of quercetin, a member of flavonoids. Taken together, these results suggest that LY294002 inhibits BCRP-mediated drug transport not by BCRP translocation through the PI3K/Akt signal but putatively as a competitive inhibitor in a major subset of cancer cells. Due to its dual effects, LY294002 could be a lead compound for developing more effective and tolerable reagents for cancer treatment.
Yasuo Imai - One of the best experts on this subject based on the ideXlab platform.
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the pi3k akt inhibitor LY294002 reverses bcrp mediated drug resistance without affecting bcrp translocation
Oncology Reports, 2012Co-Authors: Yasuo Imai, Mayumi Yoshimori, Kazunori Fukuda, Hidetsugu Yamagishi, Yoshihiko UedaAbstract:Cellular responses toward cytotoxic drugs are influenced by crosstalk between oncogenic signals and resistance mechanisms. Inhibition of the PI3K/Akt pathway is effective in sensitizing cancer cells of various organs, although the mechanisms largely remain to be elucidated. Breast cancer resistance protein (BCRP)/ABCG2, a drug efflux pump, confers resistance to multiple anticancer agents such as SN-38 and topotecan. Previous studies reported that inhibition of the PI3K/Akt pathway, by gene knockout or PI3K inhibitors, modulated BCRP-mediated drug transport via BCRP translocation in hematopoietic stem cells, renal polarized cells and glioma stem-like cells of mammals. In this study, we assessed the effects of PI3K inhibitors, LY294002 and wortmannin, on BCRP-mediated anticancer drug resistance of human cancer MCF-7 and A431 cells. LY294002, but not wortmannin, reversed the BCRP-mediated SN-38 and topotecan resistance. LY294002 treatment did not affect total or cell surface BCRP levels as determined by western blotting and flow cytometry but blocked BCRP-mediated topotecan efflux in a dose-dependent manner. Immunohistochemical analyses also demonstrated unchanged cellular BCRP distribution. BCRP overexpression in MCF-7 and A431 cells did not confer LY294002 resistance, suggesting that LY294002 is not a transported substrate of BCRP. LY294002 is a derivative of quercetin, a member of flavonoids. Taken together, these results suggest that LY294002 inhibits BCRP-mediated drug transport not by BCRP translocation through the PI3K/Akt signal but putatively as a competitive inhibitor in a major subset of cancer cells. Due to its dual effects, LY294002 could be a lead compound for developing more effective and tolerable reagents for cancer treatment.
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Abstract 5612: The PI3K/Akt inhibitor LY294002 reverses BCRP/ABCG2-mediated drug resistance without BCRP translocation
Experimental and Molecular Therapeutics, 2012Co-Authors: Yasuo Imai, Hidetsugu Yamagishi, Yoshihiko UedaAbstract:Cellular responses toward cytotoxic drugs are influenced by cross-talk between oncogenic signals and resistance mechanisms. Inhibition of the PI3K/Akt pathway is effective in sensitizing cancer cells of various organs, although the mechanisms have largely remained to be elucidated. Breast cancer resistance protein (BCRP)/ABCG2, a drug efflux pump, confers resistance to multiple anticancer agents such as SN-38 and topotecan. Previous studies reported that inhibition of the PI3K/Akt pathway, by gene knockout or PI3K inhibitors, modulated BCRP-mediated drug transport via BCRP translocation in hematopoietic stem cells, renal polarized cells, and glioma stem-like cells of mammals. In this paper, we tested reversing effects of PI3K inhibitors, LY294002 and wortmannin, on BCRP-mediated anticancer drug resistance of human cancer MCF-7 and A431 cells. LY294002 definitely reversed BCRP-mediated SN-38 and topotecan resistances but wortmannin did not. LY294002 treatment affected neither total nor cell surface BCRP levels by western blotting and flow cytometry but blocked BCRP-mediated topotecan efflux in a dose-dependent manner. Immunohistochemical analyses also demonstrated unchanged cellular BCRP distribution. BCRP overexpression in MCF-7 and A431 cells did not confer LY294002 resistance, suggesting that LY294002 would not be a transported substrate of BCRP. LY294002 is a derivative of quercetin, a member of flavonoid. Taken together, these results suggest that LY294002 inhibits BCRP-mediated drug transport not by BCRP translocation through the PI3K/Akt signal but putatively as a competitive inhibitor in a major subset of cancer cells. Due to its dual effects, LY294002 could be a lead compound for developing more effective and tolerable reagents for cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5612. doi:1538-7445.AM2012-5612
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abstract 5612 the pi3k akt inhibitor LY294002 reverses bcrp abcg2 mediated drug resistance without bcrp translocation
Cancer Research, 2012Co-Authors: Yasuo Imai, Hidetsugu Yamagishi, Yoshihiko UedaAbstract:Cellular responses toward cytotoxic drugs are influenced by cross-talk between oncogenic signals and resistance mechanisms. Inhibition of the PI3K/Akt pathway is effective in sensitizing cancer cells of various organs, although the mechanisms have largely remained to be elucidated. Breast cancer resistance protein (BCRP)/ABCG2, a drug efflux pump, confers resistance to multiple anticancer agents such as SN-38 and topotecan. Previous studies reported that inhibition of the PI3K/Akt pathway, by gene knockout or PI3K inhibitors, modulated BCRP-mediated drug transport via BCRP translocation in hematopoietic stem cells, renal polarized cells, and glioma stem-like cells of mammals. In this paper, we tested reversing effects of PI3K inhibitors, LY294002 and wortmannin, on BCRP-mediated anticancer drug resistance of human cancer MCF-7 and A431 cells. LY294002 definitely reversed BCRP-mediated SN-38 and topotecan resistances but wortmannin did not. LY294002 treatment affected neither total nor cell surface BCRP levels by western blotting and flow cytometry but blocked BCRP-mediated topotecan efflux in a dose-dependent manner. Immunohistochemical analyses also demonstrated unchanged cellular BCRP distribution. BCRP overexpression in MCF-7 and A431 cells did not confer LY294002 resistance, suggesting that LY294002 would not be a transported substrate of BCRP. LY294002 is a derivative of quercetin, a member of flavonoid. Taken together, these results suggest that LY294002 inhibits BCRP-mediated drug transport not by BCRP translocation through the PI3K/Akt signal but putatively as a competitive inhibitor in a major subset of cancer cells. Due to its dual effects, LY294002 could be a lead compound for developing more effective and tolerable reagents for cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5612. doi:1538-7445.AM2012-5612
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The PI3K/Akt inhibitor LY294002 reverses BCRP-mediated drug resistance without affecting BCRP translocation.
Oncology reports, 2012Co-Authors: Yasuo Imai, Mayumi Yoshimori, Kazunori Fukuda, Hidetsugu Yamagishi, Yoshihiko UedaAbstract:Cellular responses toward cytotoxic drugs are influenced by crosstalk between oncogenic signals and resistance mechanisms. Inhibition of the PI3K/Akt pathway is effective in sensitizing cancer cells of various organs, although the mechanisms largely remain to be elucidated. Breast cancer resistance protein (BCRP)/ABCG2, a drug efflux pump, confers resistance to multiple anticancer agents such as SN-38 and topotecan. Previous studies reported that inhibition of the PI3K/Akt pathway, by gene knockout or PI3K inhibitors, modulated BCRP-mediated drug transport via BCRP translocation in hematopoietic stem cells, renal polarized cells and glioma stem-like cells of mammals. In this study, we assessed the effects of PI3K inhibitors, LY294002 and wortmannin, on BCRP-mediated anticancer drug resistance of human cancer MCF-7 and A431 cells. LY294002, but not wortmannin, reversed the BCRP-mediated SN-38 and topotecan resistance. LY294002 treatment did not affect total or cell surface BCRP levels as determined by western blotting and flow cytometry but blocked BCRP-mediated topotecan efflux in a dose-dependent manner. Immunohistochemical analyses also demonstrated unchanged cellular BCRP distribution. BCRP overexpression in MCF-7 and A431 cells did not confer LY294002 resistance, suggesting that LY294002 is not a transported substrate of BCRP. LY294002 is a derivative of quercetin, a member of flavonoids. Taken together, these results suggest that LY294002 inhibits BCRP-mediated drug transport not by BCRP translocation through the PI3K/Akt signal but putatively as a competitive inhibitor in a major subset of cancer cells. Due to its dual effects, LY294002 could be a lead compound for developing more effective and tolerable reagents for cancer treatment.
Hidetsugu Yamagishi - One of the best experts on this subject based on the ideXlab platform.
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the pi3k akt inhibitor LY294002 reverses bcrp mediated drug resistance without affecting bcrp translocation
Oncology Reports, 2012Co-Authors: Yasuo Imai, Mayumi Yoshimori, Kazunori Fukuda, Hidetsugu Yamagishi, Yoshihiko UedaAbstract:Cellular responses toward cytotoxic drugs are influenced by crosstalk between oncogenic signals and resistance mechanisms. Inhibition of the PI3K/Akt pathway is effective in sensitizing cancer cells of various organs, although the mechanisms largely remain to be elucidated. Breast cancer resistance protein (BCRP)/ABCG2, a drug efflux pump, confers resistance to multiple anticancer agents such as SN-38 and topotecan. Previous studies reported that inhibition of the PI3K/Akt pathway, by gene knockout or PI3K inhibitors, modulated BCRP-mediated drug transport via BCRP translocation in hematopoietic stem cells, renal polarized cells and glioma stem-like cells of mammals. In this study, we assessed the effects of PI3K inhibitors, LY294002 and wortmannin, on BCRP-mediated anticancer drug resistance of human cancer MCF-7 and A431 cells. LY294002, but not wortmannin, reversed the BCRP-mediated SN-38 and topotecan resistance. LY294002 treatment did not affect total or cell surface BCRP levels as determined by western blotting and flow cytometry but blocked BCRP-mediated topotecan efflux in a dose-dependent manner. Immunohistochemical analyses also demonstrated unchanged cellular BCRP distribution. BCRP overexpression in MCF-7 and A431 cells did not confer LY294002 resistance, suggesting that LY294002 is not a transported substrate of BCRP. LY294002 is a derivative of quercetin, a member of flavonoids. Taken together, these results suggest that LY294002 inhibits BCRP-mediated drug transport not by BCRP translocation through the PI3K/Akt signal but putatively as a competitive inhibitor in a major subset of cancer cells. Due to its dual effects, LY294002 could be a lead compound for developing more effective and tolerable reagents for cancer treatment.
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Abstract 5612: The PI3K/Akt inhibitor LY294002 reverses BCRP/ABCG2-mediated drug resistance without BCRP translocation
Experimental and Molecular Therapeutics, 2012Co-Authors: Yasuo Imai, Hidetsugu Yamagishi, Yoshihiko UedaAbstract:Cellular responses toward cytotoxic drugs are influenced by cross-talk between oncogenic signals and resistance mechanisms. Inhibition of the PI3K/Akt pathway is effective in sensitizing cancer cells of various organs, although the mechanisms have largely remained to be elucidated. Breast cancer resistance protein (BCRP)/ABCG2, a drug efflux pump, confers resistance to multiple anticancer agents such as SN-38 and topotecan. Previous studies reported that inhibition of the PI3K/Akt pathway, by gene knockout or PI3K inhibitors, modulated BCRP-mediated drug transport via BCRP translocation in hematopoietic stem cells, renal polarized cells, and glioma stem-like cells of mammals. In this paper, we tested reversing effects of PI3K inhibitors, LY294002 and wortmannin, on BCRP-mediated anticancer drug resistance of human cancer MCF-7 and A431 cells. LY294002 definitely reversed BCRP-mediated SN-38 and topotecan resistances but wortmannin did not. LY294002 treatment affected neither total nor cell surface BCRP levels by western blotting and flow cytometry but blocked BCRP-mediated topotecan efflux in a dose-dependent manner. Immunohistochemical analyses also demonstrated unchanged cellular BCRP distribution. BCRP overexpression in MCF-7 and A431 cells did not confer LY294002 resistance, suggesting that LY294002 would not be a transported substrate of BCRP. LY294002 is a derivative of quercetin, a member of flavonoid. Taken together, these results suggest that LY294002 inhibits BCRP-mediated drug transport not by BCRP translocation through the PI3K/Akt signal but putatively as a competitive inhibitor in a major subset of cancer cells. Due to its dual effects, LY294002 could be a lead compound for developing more effective and tolerable reagents for cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5612. doi:1538-7445.AM2012-5612
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abstract 5612 the pi3k akt inhibitor LY294002 reverses bcrp abcg2 mediated drug resistance without bcrp translocation
Cancer Research, 2012Co-Authors: Yasuo Imai, Hidetsugu Yamagishi, Yoshihiko UedaAbstract:Cellular responses toward cytotoxic drugs are influenced by cross-talk between oncogenic signals and resistance mechanisms. Inhibition of the PI3K/Akt pathway is effective in sensitizing cancer cells of various organs, although the mechanisms have largely remained to be elucidated. Breast cancer resistance protein (BCRP)/ABCG2, a drug efflux pump, confers resistance to multiple anticancer agents such as SN-38 and topotecan. Previous studies reported that inhibition of the PI3K/Akt pathway, by gene knockout or PI3K inhibitors, modulated BCRP-mediated drug transport via BCRP translocation in hematopoietic stem cells, renal polarized cells, and glioma stem-like cells of mammals. In this paper, we tested reversing effects of PI3K inhibitors, LY294002 and wortmannin, on BCRP-mediated anticancer drug resistance of human cancer MCF-7 and A431 cells. LY294002 definitely reversed BCRP-mediated SN-38 and topotecan resistances but wortmannin did not. LY294002 treatment affected neither total nor cell surface BCRP levels by western blotting and flow cytometry but blocked BCRP-mediated topotecan efflux in a dose-dependent manner. Immunohistochemical analyses also demonstrated unchanged cellular BCRP distribution. BCRP overexpression in MCF-7 and A431 cells did not confer LY294002 resistance, suggesting that LY294002 would not be a transported substrate of BCRP. LY294002 is a derivative of quercetin, a member of flavonoid. Taken together, these results suggest that LY294002 inhibits BCRP-mediated drug transport not by BCRP translocation through the PI3K/Akt signal but putatively as a competitive inhibitor in a major subset of cancer cells. Due to its dual effects, LY294002 could be a lead compound for developing more effective and tolerable reagents for cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5612. doi:1538-7445.AM2012-5612
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The PI3K/Akt inhibitor LY294002 reverses BCRP-mediated drug resistance without affecting BCRP translocation.
Oncology reports, 2012Co-Authors: Yasuo Imai, Mayumi Yoshimori, Kazunori Fukuda, Hidetsugu Yamagishi, Yoshihiko UedaAbstract:Cellular responses toward cytotoxic drugs are influenced by crosstalk between oncogenic signals and resistance mechanisms. Inhibition of the PI3K/Akt pathway is effective in sensitizing cancer cells of various organs, although the mechanisms largely remain to be elucidated. Breast cancer resistance protein (BCRP)/ABCG2, a drug efflux pump, confers resistance to multiple anticancer agents such as SN-38 and topotecan. Previous studies reported that inhibition of the PI3K/Akt pathway, by gene knockout or PI3K inhibitors, modulated BCRP-mediated drug transport via BCRP translocation in hematopoietic stem cells, renal polarized cells and glioma stem-like cells of mammals. In this study, we assessed the effects of PI3K inhibitors, LY294002 and wortmannin, on BCRP-mediated anticancer drug resistance of human cancer MCF-7 and A431 cells. LY294002, but not wortmannin, reversed the BCRP-mediated SN-38 and topotecan resistance. LY294002 treatment did not affect total or cell surface BCRP levels as determined by western blotting and flow cytometry but blocked BCRP-mediated topotecan efflux in a dose-dependent manner. Immunohistochemical analyses also demonstrated unchanged cellular BCRP distribution. BCRP overexpression in MCF-7 and A431 cells did not confer LY294002 resistance, suggesting that LY294002 is not a transported substrate of BCRP. LY294002 is a derivative of quercetin, a member of flavonoids. Taken together, these results suggest that LY294002 inhibits BCRP-mediated drug transport not by BCRP translocation through the PI3K/Akt signal but putatively as a competitive inhibitor in a major subset of cancer cells. Due to its dual effects, LY294002 could be a lead compound for developing more effective and tolerable reagents for cancer treatment.
Mayumi Yoshimori - One of the best experts on this subject based on the ideXlab platform.
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the pi3k akt inhibitor LY294002 reverses bcrp mediated drug resistance without affecting bcrp translocation
Oncology Reports, 2012Co-Authors: Yasuo Imai, Mayumi Yoshimori, Kazunori Fukuda, Hidetsugu Yamagishi, Yoshihiko UedaAbstract:Cellular responses toward cytotoxic drugs are influenced by crosstalk between oncogenic signals and resistance mechanisms. Inhibition of the PI3K/Akt pathway is effective in sensitizing cancer cells of various organs, although the mechanisms largely remain to be elucidated. Breast cancer resistance protein (BCRP)/ABCG2, a drug efflux pump, confers resistance to multiple anticancer agents such as SN-38 and topotecan. Previous studies reported that inhibition of the PI3K/Akt pathway, by gene knockout or PI3K inhibitors, modulated BCRP-mediated drug transport via BCRP translocation in hematopoietic stem cells, renal polarized cells and glioma stem-like cells of mammals. In this study, we assessed the effects of PI3K inhibitors, LY294002 and wortmannin, on BCRP-mediated anticancer drug resistance of human cancer MCF-7 and A431 cells. LY294002, but not wortmannin, reversed the BCRP-mediated SN-38 and topotecan resistance. LY294002 treatment did not affect total or cell surface BCRP levels as determined by western blotting and flow cytometry but blocked BCRP-mediated topotecan efflux in a dose-dependent manner. Immunohistochemical analyses also demonstrated unchanged cellular BCRP distribution. BCRP overexpression in MCF-7 and A431 cells did not confer LY294002 resistance, suggesting that LY294002 is not a transported substrate of BCRP. LY294002 is a derivative of quercetin, a member of flavonoids. Taken together, these results suggest that LY294002 inhibits BCRP-mediated drug transport not by BCRP translocation through the PI3K/Akt signal but putatively as a competitive inhibitor in a major subset of cancer cells. Due to its dual effects, LY294002 could be a lead compound for developing more effective and tolerable reagents for cancer treatment.
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The PI3K/Akt inhibitor LY294002 reverses BCRP-mediated drug resistance without affecting BCRP translocation.
Oncology reports, 2012Co-Authors: Yasuo Imai, Mayumi Yoshimori, Kazunori Fukuda, Hidetsugu Yamagishi, Yoshihiko UedaAbstract:Cellular responses toward cytotoxic drugs are influenced by crosstalk between oncogenic signals and resistance mechanisms. Inhibition of the PI3K/Akt pathway is effective in sensitizing cancer cells of various organs, although the mechanisms largely remain to be elucidated. Breast cancer resistance protein (BCRP)/ABCG2, a drug efflux pump, confers resistance to multiple anticancer agents such as SN-38 and topotecan. Previous studies reported that inhibition of the PI3K/Akt pathway, by gene knockout or PI3K inhibitors, modulated BCRP-mediated drug transport via BCRP translocation in hematopoietic stem cells, renal polarized cells and glioma stem-like cells of mammals. In this study, we assessed the effects of PI3K inhibitors, LY294002 and wortmannin, on BCRP-mediated anticancer drug resistance of human cancer MCF-7 and A431 cells. LY294002, but not wortmannin, reversed the BCRP-mediated SN-38 and topotecan resistance. LY294002 treatment did not affect total or cell surface BCRP levels as determined by western blotting and flow cytometry but blocked BCRP-mediated topotecan efflux in a dose-dependent manner. Immunohistochemical analyses also demonstrated unchanged cellular BCRP distribution. BCRP overexpression in MCF-7 and A431 cells did not confer LY294002 resistance, suggesting that LY294002 is not a transported substrate of BCRP. LY294002 is a derivative of quercetin, a member of flavonoids. Taken together, these results suggest that LY294002 inhibits BCRP-mediated drug transport not by BCRP translocation through the PI3K/Akt signal but putatively as a competitive inhibitor in a major subset of cancer cells. Due to its dual effects, LY294002 could be a lead compound for developing more effective and tolerable reagents for cancer treatment.
Kazunori Fukuda - One of the best experts on this subject based on the ideXlab platform.
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the pi3k akt inhibitor LY294002 reverses bcrp mediated drug resistance without affecting bcrp translocation
Oncology Reports, 2012Co-Authors: Yasuo Imai, Mayumi Yoshimori, Kazunori Fukuda, Hidetsugu Yamagishi, Yoshihiko UedaAbstract:Cellular responses toward cytotoxic drugs are influenced by crosstalk between oncogenic signals and resistance mechanisms. Inhibition of the PI3K/Akt pathway is effective in sensitizing cancer cells of various organs, although the mechanisms largely remain to be elucidated. Breast cancer resistance protein (BCRP)/ABCG2, a drug efflux pump, confers resistance to multiple anticancer agents such as SN-38 and topotecan. Previous studies reported that inhibition of the PI3K/Akt pathway, by gene knockout or PI3K inhibitors, modulated BCRP-mediated drug transport via BCRP translocation in hematopoietic stem cells, renal polarized cells and glioma stem-like cells of mammals. In this study, we assessed the effects of PI3K inhibitors, LY294002 and wortmannin, on BCRP-mediated anticancer drug resistance of human cancer MCF-7 and A431 cells. LY294002, but not wortmannin, reversed the BCRP-mediated SN-38 and topotecan resistance. LY294002 treatment did not affect total or cell surface BCRP levels as determined by western blotting and flow cytometry but blocked BCRP-mediated topotecan efflux in a dose-dependent manner. Immunohistochemical analyses also demonstrated unchanged cellular BCRP distribution. BCRP overexpression in MCF-7 and A431 cells did not confer LY294002 resistance, suggesting that LY294002 is not a transported substrate of BCRP. LY294002 is a derivative of quercetin, a member of flavonoids. Taken together, these results suggest that LY294002 inhibits BCRP-mediated drug transport not by BCRP translocation through the PI3K/Akt signal but putatively as a competitive inhibitor in a major subset of cancer cells. Due to its dual effects, LY294002 could be a lead compound for developing more effective and tolerable reagents for cancer treatment.
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The PI3K/Akt inhibitor LY294002 reverses BCRP-mediated drug resistance without affecting BCRP translocation.
Oncology reports, 2012Co-Authors: Yasuo Imai, Mayumi Yoshimori, Kazunori Fukuda, Hidetsugu Yamagishi, Yoshihiko UedaAbstract:Cellular responses toward cytotoxic drugs are influenced by crosstalk between oncogenic signals and resistance mechanisms. Inhibition of the PI3K/Akt pathway is effective in sensitizing cancer cells of various organs, although the mechanisms largely remain to be elucidated. Breast cancer resistance protein (BCRP)/ABCG2, a drug efflux pump, confers resistance to multiple anticancer agents such as SN-38 and topotecan. Previous studies reported that inhibition of the PI3K/Akt pathway, by gene knockout or PI3K inhibitors, modulated BCRP-mediated drug transport via BCRP translocation in hematopoietic stem cells, renal polarized cells and glioma stem-like cells of mammals. In this study, we assessed the effects of PI3K inhibitors, LY294002 and wortmannin, on BCRP-mediated anticancer drug resistance of human cancer MCF-7 and A431 cells. LY294002, but not wortmannin, reversed the BCRP-mediated SN-38 and topotecan resistance. LY294002 treatment did not affect total or cell surface BCRP levels as determined by western blotting and flow cytometry but blocked BCRP-mediated topotecan efflux in a dose-dependent manner. Immunohistochemical analyses also demonstrated unchanged cellular BCRP distribution. BCRP overexpression in MCF-7 and A431 cells did not confer LY294002 resistance, suggesting that LY294002 is not a transported substrate of BCRP. LY294002 is a derivative of quercetin, a member of flavonoids. Taken together, these results suggest that LY294002 inhibits BCRP-mediated drug transport not by BCRP translocation through the PI3K/Akt signal but putatively as a competitive inhibitor in a major subset of cancer cells. Due to its dual effects, LY294002 could be a lead compound for developing more effective and tolerable reagents for cancer treatment.
