title: Low doses of PEG-coated gold nanoparticles sensitize solid tumors to cold plasma by blocking the PI3K/AKT-driven signaling axis to suppress cellular transformation by inhibiting growth and EMT.
abstract: Metastasis, the primary cause of tumor cell transformation, is often activated during cancer invasion and progression and is associated with poor therapeutic outcomes. The effects of combined treatments that included PEG-coated gold nanoparticles (GNP) and cold plasma on epithelial-mesenchymal transition (EMT) and the maintenance of cancer stem cells (CSC) have not been described so far. Here, we report that co-treatment with GNP and cold plasma inhibited proliferation in cancer cells by abolishing the activation of the PI3K/AKT signaling axis. In addition, co-treatment reversed EMT in solid tumor cells by reducing the secretion of a number of proteins, resulting in the upregulation of epithelial markers such as E-cadherin along with down-regulation of N-Cadherin, Slug and Zeb-1. The inhibition of the PI3K/AKT pathway and the reversal of EMT by co-treatment prevented tumor cells growth in solid tumors. Furthermore, we show that GNP and plasma also suppresses tumor growth by decreasing mesenchymal markers in tumor xenograft mice models. Importantly, co-treatment resulted in a substantial decrease in sphere formation and the self-renewal capacity of glioma-like stem cells. Together, these results indicate a direct link between a decrease of EMT and an increase in cell death in solid tumors following co-treatment with cold plasma and GNP.
authors.affiliation: Plasma Bioscience Research Center, Department of Electrical and Biological Physics, Kwangwoon University, Seoul, 139-701, Republic of Korea. Electronic address: kaushik.nagendra@kw.ac.kr.
authors.forename: Nagendra Kumar
authors.initials: NK
authors.lastname: Kaushik
authors.affiliation: Plasma Bioscience Research Center, Department of Electrical and Biological Physics, Kwangwoon University, Seoul, 139-701, Republic of Korea; Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, 133-791, Republic of Korea.
authors.forename: Neha
authors.initials: N
authors.lastname: Kaushik
authors.affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, 133-791, Republic of Korea.
authors.forename: Ki Chun
authors.initials: KC
authors.lastname: Yoo
authors.affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, 133-791, Republic of Korea.
authors.forename: Nizam
authors.initials: N
authors.lastname: Uddin
authors.affiliation: Plasma Bioscience Research Center, Department of Electrical and Biological Physics, Kwangwoon University, Seoul, 139-701, Republic of Korea.
authors.forename: Ju Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, 133-791, Republic of Korea. Electronic address: sj0420@hanyang.ac.kr.
authors.forename: Su Jae
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Plasma Bioscience Research Center, Department of Electrical and Biological Physics, Kwangwoon University, Seoul, 139-701, Republic of Korea. Electronic address: ehchoi@kw.ac.kr.
authors.forename: Eun Ha
authors.initials: EH
authors.lastname: Choi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006046:Gold / Q000627:therapeutic use*; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D058626:Plasma Gases / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D006046:Gold; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D058626:Plasma Gases; D051057:Proto-Oncogene Proteins c-akt
keywords: Cold plasma; Epithelial–mesenchymal transition; Glioma-like stem cells; Gold nanoparticles; Solid cancers; Stemness