Scorpion Venom Analgesic Peptide, BmK AGAP Inhibits Stemness, and Epithelial-Mesenchymal Transition by Down-Regulating PTX3 in Breast Cancer

• Main Authors: Sylvanus Kampo, Bulbul Ahmmed, Tingting Zhou, Lawrence Owusu, Thomas Winsum Anabah, Natacha Raissa Doudou, Eugene Dogkotenge Kuugbee, Yong Cui, Zhili Lu, Qiu Yan, Qing-Ping Wen
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-01-01
• Series: Frontiers in Oncology
• Subjects: scorpion venom analgesic peptide; rBmK AGAP; stemness; epithelial-mesenchymal transition; pentraxin 3; Wnt/β-catenin signaling
• Online Access: https://www.frontiersin.org/article/10.3389/fonc.2019.00021/full

A scorpion peptide reported to exhibit both analgesic and antitumor activity in animal models may present as an alternative therapeutic agent for breast cancer. We aimed to investigate the effect of Buthus martensii Karsch antitumor-analgesic peptide (BmK AGAP) on breast cancer cell stemness and epithelial-mesenchymal transition (EMT). We treated MCF-7 and MDA-MB-231 cells with different concentrations of rBmK AGAP and observed that rBmK AGAP inhibited cancer cell stemness, epithelial-mesenchymal transition (EMT), migration, and invasion. Analysis by qPCR, ELISA, western blot, immunofluorescence staining, sphere formation, colony assay, transwell migration, and invasion assays demonstrated rBmK AGAP treatment decreased the expressions of Oct4, Sox2, N-cadherin, Snail, and increased the expression of E-cadherin. rBmK AGAP inhibited breast cancer cell stemness, EMT, migration, and invasion by down-regulating PTX3 through NF-κB and Wnt/β-catenin signaling Pathway in vitro and in vivo. Xenograft tumor model confirmed inhibition of tumor growth, stem-like features, and EMT by rBmK AGAP. Thus, rBmK AGAP is a potential therapeutic agent against breast cancer and related pain.