Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Antitumor Effect of Novel Berberine Analogues in a Canine Mammary Tumor Cell Line and in Zebrafish Reporters via Wnt/β-Catenin and Hippo Pathways

Alessandro Sammarco
,
Giorgia Beffagna
,
Roberta Sacchetto
ORCID logo ,
Andrea Vettori
ORCID logo ,
Federico Bonsembiante
ORCID logo ,
Giulia Scarin
,
Maria Elena Gelain
ORCID logo ,
Laura Cavicchioli
ORCID logo ,
Silvia Ferro
ORCID logo ,
Cristina Geroni
,
Paolo Lombardi
ORCID logo ,
Valentina Zappulli
* ORCID logo
Version 1 : Received: 21 November 2023 / Approved: 22 November 2023 / Online: 22 November 2023 (11:45:04 CET)

A peer-reviewed article of this Preprint also exists.

Sammarco, A.; Beffagna, G.; Sacchetto, R.; Vettori, A.; Bonsembiante, F.; Scarin, G.; Gelain, M.E.; Cavicchioli, L.; Ferro, S.; Geroni, C.; Lombardi, P.; Zappulli, V. Antitumor Effect of Berberine Analogs in a Canine Mammary Tumor Cell Line and in Zebrafish Reporters via Wnt/β-Catenin and Hippo Pathways. Biomedicines 2023, 11, 3317. Sammarco, A.; Beffagna, G.; Sacchetto, R.; Vettori, A.; Bonsembiante, F.; Scarin, G.; Gelain, M.E.; Cavicchioli, L.; Ferro, S.; Geroni, C.; Lombardi, P.; Zappulli, V. Antitumor Effect of Berberine Analogs in a Canine Mammary Tumor Cell Line and in Zebrafish Reporters via Wnt/β-Catenin and Hippo Pathways. Biomedicines 2023, 11, 3317.

Abstract

The heterogeneous nature of human breast cancer (HBC) can still lead to therapy inefficacy and high le-thality and new therapeutics are needed as well as new spontaneous animal models to benefit translational HBC research. Dogs are primarily investigated since they spontaneously develop tumors which 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 in rodent animal models. In this study, we report the antiproliferative activity and mechanism of action of berberine, of its active metabolite berberrubine, and of eight analogues, 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 analogues on cell viability, via induction of apoptosis, also identifying their role in inhibiting the Wnt/β-catenin pathway and activating the Hippo signals with a downstream reduction of CTGF expres-sion. Particularly the berberine analogues NAX035 and NAX057 show the highest therapeutic efficacy, de-serving further analyses to elucidate their mechanism of action more in detail, and in vivo studies on spon-taneous neoplastic diseases aiming at improving veterinary treatments of cancer as well as translational cancer research.

Keywords

berberine derivates; dog; mammary tumors; zebrafish; Hippo; Wnt; β-catenin

Subject

Medicine and Pharmacology, Veterinary Medicine

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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