Antitumor Effect of Berberine Analogs in a Canine Mammary Tumor Cell Line and in Zebrafish Reporters via Wnt/β-Catenin and Hippo Pathways
The heterogeneous nature of human breast cancer (HBC) can still lead to therapy inefficacy and high lethality, and new therapeutics as well as new spontaneous animal models are needed to benefit translational HBC research. Dogs are primarily investigated since they spontaneously develop tumors that...
Ausführliche Beschreibung
Autor*in: |
Alessandro Sammarco [verfasserIn] Giorgia Beffagna [verfasserIn] Roberta Sacchetto [verfasserIn] Andrea Vettori [verfasserIn] Federico Bonsembiante [verfasserIn] Giulia Scarin [verfasserIn] Maria Elena Gelain [verfasserIn] Laura Cavicchioli [verfasserIn] Silvia Ferro [verfasserIn] Cristina Geroni [verfasserIn] Paolo Lombardi [verfasserIn] Valentina Zappulli [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2023 |
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Schlagwörter: |
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Übergeordnetes Werk: |
In: Biomedicines - MDPI AG, 2014, 11(2023), 12, p 3317 |
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Übergeordnetes Werk: |
volume:11 ; year:2023 ; number:12, p 3317 |
Links: |
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DOI / URN: |
10.3390/biomedicines11123317 |
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Katalog-ID: |
DOAJ09890633X |
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10.3390/biomedicines11123317 doi (DE-627)DOAJ09890633X (DE-599)DOAJ8f7540fa1e4c43f4a994d739d2f4accc DE-627 ger DE-627 rakwb eng QH301-705.5 Alessandro Sammarco verfasserin aut Antitumor Effect of Berberine Analogs in a Canine Mammary Tumor Cell Line and in Zebrafish Reporters via Wnt/β-Catenin and Hippo Pathways 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The heterogeneous nature of human breast cancer (HBC) can still lead to therapy inefficacy and high lethality, and new therapeutics as well as new spontaneous animal models are needed to benefit translational HBC research. Dogs are primarily investigated since they spontaneously develop tumors that share many features with human cancers. In recent years, different natural phytochemicals including berberine, a plant alkaloid, have been reported to have antiproliferative activity in vitro in human cancers and rodent animal models. In this study, we report the antiproliferative activity and mechanism of action of berberine, its active metabolite berberrubine, and eight analogs, on a canine mammary carcinoma cell line and in transgenic zebrafish models. We demonstrate both in vitro and in vivo the significant effects of specific analogs on cell viability via the induction of apoptosis, also identifying their role in inhibiting the Wnt/β-catenin pathway and activating the Hippo signals with a downstream reduction in <i<CTGF</i< expression. In particular, the berberine analogs NAX035 and NAX057 show the highest therapeutic efficacy, deserving further analyses to elucidate their mechanism of action more in detail, and in vivo studies on spontaneous neoplastic diseases are needed, aiming at improving veterinary treatments of cancer as well as translational cancer research. berberine derivates dog mammary tumors zebrafish Hippo Wnt Biology (General) Giorgia Beffagna verfasserin aut Roberta Sacchetto verfasserin aut Andrea Vettori verfasserin aut Federico Bonsembiante verfasserin aut Giulia Scarin verfasserin aut Maria Elena Gelain verfasserin aut Laura Cavicchioli verfasserin aut Silvia Ferro verfasserin aut Cristina Geroni verfasserin aut Paolo Lombardi verfasserin aut Valentina Zappulli verfasserin aut In Biomedicines MDPI AG, 2014 11(2023), 12, p 3317 (DE-627)750370483 (DE-600)2720867-9 22279059 nnns volume:11 year:2023 number:12, p 3317 https://doi.org/10.3390/biomedicines11123317 kostenfrei https://doaj.org/article/8f7540fa1e4c43f4a994d739d2f4accc kostenfrei https://www.mdpi.com/2227-9059/11/12/3317 kostenfrei https://doaj.org/toc/2227-9059 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2023 12, p 3317 |
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10.3390/biomedicines11123317 doi (DE-627)DOAJ09890633X (DE-599)DOAJ8f7540fa1e4c43f4a994d739d2f4accc DE-627 ger DE-627 rakwb eng QH301-705.5 Alessandro Sammarco verfasserin aut Antitumor Effect of Berberine Analogs in a Canine Mammary Tumor Cell Line and in Zebrafish Reporters via Wnt/β-Catenin and Hippo Pathways 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The heterogeneous nature of human breast cancer (HBC) can still lead to therapy inefficacy and high lethality, and new therapeutics as well as new spontaneous animal models are needed to benefit translational HBC research. Dogs are primarily investigated since they spontaneously develop tumors that share many features with human cancers. In recent years, different natural phytochemicals including berberine, a plant alkaloid, have been reported to have antiproliferative activity in vitro in human cancers and rodent animal models. In this study, we report the antiproliferative activity and mechanism of action of berberine, its active metabolite berberrubine, and eight analogs, on a canine mammary carcinoma cell line and in transgenic zebrafish models. We demonstrate both in vitro and in vivo the significant effects of specific analogs on cell viability via the induction of apoptosis, also identifying their role in inhibiting the Wnt/β-catenin pathway and activating the Hippo signals with a downstream reduction in <i<CTGF</i< expression. In particular, the berberine analogs NAX035 and NAX057 show the highest therapeutic efficacy, deserving further analyses to elucidate their mechanism of action more in detail, and in vivo studies on spontaneous neoplastic diseases are needed, aiming at improving veterinary treatments of cancer as well as translational cancer research. berberine derivates dog mammary tumors zebrafish Hippo Wnt Biology (General) Giorgia Beffagna verfasserin aut Roberta Sacchetto verfasserin aut Andrea Vettori verfasserin aut Federico Bonsembiante verfasserin aut Giulia Scarin verfasserin aut Maria Elena Gelain verfasserin aut Laura Cavicchioli verfasserin aut Silvia Ferro verfasserin aut Cristina Geroni verfasserin aut Paolo Lombardi verfasserin aut Valentina Zappulli verfasserin aut In Biomedicines MDPI AG, 2014 11(2023), 12, p 3317 (DE-627)750370483 (DE-600)2720867-9 22279059 nnns volume:11 year:2023 number:12, p 3317 https://doi.org/10.3390/biomedicines11123317 kostenfrei https://doaj.org/article/8f7540fa1e4c43f4a994d739d2f4accc kostenfrei https://www.mdpi.com/2227-9059/11/12/3317 kostenfrei https://doaj.org/toc/2227-9059 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2023 12, p 3317 |
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Alessandro Sammarco @@aut@@ Giorgia Beffagna @@aut@@ Roberta Sacchetto @@aut@@ Andrea Vettori @@aut@@ Federico Bonsembiante @@aut@@ Giulia Scarin @@aut@@ Maria Elena Gelain @@aut@@ Laura Cavicchioli @@aut@@ Silvia Ferro @@aut@@ Cristina Geroni @@aut@@ Paolo Lombardi @@aut@@ Valentina Zappulli @@aut@@ |
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Antitumor Effect of Berberine Analogs in a Canine Mammary Tumor Cell Line and in Zebrafish Reporters via Wnt/β-Catenin and Hippo Pathways |
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The heterogeneous nature of human breast cancer (HBC) can still lead to therapy inefficacy and high lethality, and new therapeutics as well as new spontaneous animal models are needed to benefit translational HBC research. Dogs are primarily investigated since they spontaneously develop tumors that share many features with human cancers. In recent years, different natural phytochemicals including berberine, a plant alkaloid, have been reported to have antiproliferative activity in vitro in human cancers and rodent animal models. In this study, we report the antiproliferative activity and mechanism of action of berberine, its active metabolite berberrubine, and eight analogs, on a canine mammary carcinoma cell line and in transgenic zebrafish models. We demonstrate both in vitro and in vivo the significant effects of specific analogs on cell viability via the induction of apoptosis, also identifying their role in inhibiting the Wnt/β-catenin pathway and activating the Hippo signals with a downstream reduction in <i<CTGF</i< expression. In particular, the berberine analogs NAX035 and NAX057 show the highest therapeutic efficacy, deserving further analyses to elucidate their mechanism of action more in detail, and in vivo studies on spontaneous neoplastic diseases are needed, aiming at improving veterinary treatments of cancer as well as translational cancer research. |
abstractGer |
The heterogeneous nature of human breast cancer (HBC) can still lead to therapy inefficacy and high lethality, and new therapeutics as well as new spontaneous animal models are needed to benefit translational HBC research. Dogs are primarily investigated since they spontaneously develop tumors that share many features with human cancers. In recent years, different natural phytochemicals including berberine, a plant alkaloid, have been reported to have antiproliferative activity in vitro in human cancers and rodent animal models. In this study, we report the antiproliferative activity and mechanism of action of berberine, its active metabolite berberrubine, and eight analogs, on a canine mammary carcinoma cell line and in transgenic zebrafish models. We demonstrate both in vitro and in vivo the significant effects of specific analogs on cell viability via the induction of apoptosis, also identifying their role in inhibiting the Wnt/β-catenin pathway and activating the Hippo signals with a downstream reduction in <i<CTGF</i< expression. In particular, the berberine analogs NAX035 and NAX057 show the highest therapeutic efficacy, deserving further analyses to elucidate their mechanism of action more in detail, and in vivo studies on spontaneous neoplastic diseases are needed, aiming at improving veterinary treatments of cancer as well as translational cancer research. |
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The heterogeneous nature of human breast cancer (HBC) can still lead to therapy inefficacy and high lethality, and new therapeutics as well as new spontaneous animal models are needed to benefit translational HBC research. Dogs are primarily investigated since they spontaneously develop tumors that share many features with human cancers. In recent years, different natural phytochemicals including berberine, a plant alkaloid, have been reported to have antiproliferative activity in vitro in human cancers and rodent animal models. In this study, we report the antiproliferative activity and mechanism of action of berberine, its active metabolite berberrubine, and eight analogs, on a canine mammary carcinoma cell line and in transgenic zebrafish models. We demonstrate both in vitro and in vivo the significant effects of specific analogs on cell viability via the induction of apoptosis, also identifying their role in inhibiting the Wnt/β-catenin pathway and activating the Hippo signals with a downstream reduction in <i<CTGF</i< expression. In particular, the berberine analogs NAX035 and NAX057 show the highest therapeutic efficacy, deserving further analyses to elucidate their mechanism of action more in detail, and in vivo studies on spontaneous neoplastic diseases are needed, aiming at improving veterinary treatments of cancer as well as translational cancer research. |
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