Lectin from Laetiporus sulphureus effectively inhibits angiogenesis and tumor development in the zebrafish xenograft models of colorectal carcinoma and melanoma

• Published in: International journal of biological macromolecules Vol. 148; pp. 129 - 139
• Main Authors: Petrović, Jovana, Glamočlija, Jasmina, Ilić-Tomić, Tatjana, Soković, Marina, Robajac, Dragana, Nedić, Olgica, Pavić, Aleksandar
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2020
• Subjects: Angiogenesis Inhibitors - pharmacology; Animals; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cisplatin - pharmacology; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; Humans; in vivo angiogenesis; in vivo anticancer activity; in vivo toxicity; Laetiporus sulphureus; Lectin; Lectins - pharmacology; Melanoma - drug therapy; Melanoma - pathology; Mice; Neovascularization, Pathologic - drug therapy; Polyporales - chemistry; Xenograft Model Antitumor Assays; Zebrafish; Lectin; Zebrafish; Laetiporus sulphureus; in vivo anticancer activity; in vivo toxicity; in vivo angiogenesis
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2020.01.033

In spite of extensive usage of Laetiporus sulphureus (sulphur polypore) in traditional European and Asian ethno-medicine for centuries, its anticancer therapeutic potential and toxicity profile remained explored in animal models. Herein, using zebrafish (Danio rerio), as a preclinical animal model, we demonstrated that L. sulphureus lectin (LSL) and ethanol extract (LSE) are non-toxic at high doses up to 400–500 μg/mL, while they effectively inhibited angiogenesis and cancer development at much lower doses. Lectin showed 74-fold higher anti-angiogenic potency than the extract, and even 378-fold higher therapeutic potential than sunitinib-malate, cardiotoxic and myelosupressive anti-angiogenic drug of clinical relevance. Using wound healing and MTT assays, we proved LSL's strong antimigratory effect and selective endothelial cytotoxicity in relation to lung fibroblasts. In addition, employing the zebrafish xenograft models, we demonstrated that LSL almost completely reduced growth, neovascularization and metastasis of human colorectal carcinoma and mouse melanoma. Even more, LSL exerted 8-fold higher potency towards colorectal carcinoma than melanoma, showing markedly higher activity than cisplatin, while LSE failed to express any anticancer activity. Accompanied with non-toxic response, including neutropenia and inflammation, the results of this study strongly imply that LSL could be used as safe adjuvant in chemotherapy against colorectal carcinoma and melanoma. [Display omitted] •Laetiporus sulphureus lectin (LSL) and ethanol extract (LSE) are no toxic in vivo.•LSL prevents growth and metastasis of HCT-116 and B16 cells in zebrafish xenografts.•LSL and LSE effectively inhibit angiogenesis in vivo and endothelial cells migration.•LSL and LSE have higher therapeutic potential than drug sunitinib-malate or cisplatin.