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

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

doi:10.3389/fonc.2019.00021

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

Front Oncol. 2019 Jan 25:9:21. doi: 10.3389/fonc.2019.00021. eCollection 2019.

Authors

Sylvanus Kampo^{1

2

3}, Bulbul Ahmmed⁴, Tingting Zhou^{1

2}, Lawrence Owusu⁵, Thomas Winsum Anabah³, Natacha Raissa Doudou⁶, Eugene Dogkotenge Kuugbee⁷, Yong Cui⁸, Zhili Lu⁹, Qiu Yan⁴, Qing-Ping Wen^{1

2}

Affiliations

¹ Department of Anesthesiology, Dalian Medical University, Dalian, China.
² Department of Anesthesiology, First Affiliated Hospital of Dalian Medical University, Dalian, China.
³ Department of Anesthesia and Intensive Care, School of Medicine and Health Science, University for Development Studies, Tamale, Ghana.
⁴ Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, China.
⁵ Department of Biotechnology, Dalian Medical University, Dalian, China.
⁶ Department of Radiology, Dalian Medical University, Dalian, China.
⁷ Department of Clinical Microbiology, School of Medicine and Health Science, University for Development Studies, Tamale, Ghana.
⁸ School of Life Science and Bio-pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.
⁹ Department of Ophthalmology, First Affiliated Hospital of Dalian Medical University, Dalian, China.

Abstract

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.

Keywords: Wnt/β-catenin signaling; breast cancer; epithelial-mesenchymal transition; pentraxin 3; rBmK AGAP; scorpion venom analgesic peptide; stemness; transcription factor NF-κB.