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Molecular Targeting of H/MDM-2 Oncoprotein in Human Colon Cancer Cells and Stem-like Colonic Epithelial-derived Progenitor Cells
Journal article   Open access   Peer reviewed

Molecular Targeting of H/MDM-2 Oncoprotein in Human Colon Cancer Cells and Stem-like Colonic Epithelial-derived Progenitor Cells

Anusha Thadi, William F Morano, Marian Khalili, Blake D Babcock, Mohammad F Shaikh, Deshka S Foster, Yelena Piazza, Elizabeth M Gleeson, Eve Goldstein, Lindsay Steele, …
Anticancer research, v 41(1), pp 27-42
Jan 2021
DOI: https://doi.org/10.21873/anticanres.14749
PMID: 33419797
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.21873/anticanres.14749View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open

Abstract

Animals Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Biomarkers Biomarkers, Tumor Cell Line, Tumor Colonic Neoplasms - drug therapy Colonic Neoplasms - etiology Colonic Neoplasms - metabolism Colonic Neoplasms - pathology Disease Models, Animal Humans Hyaluronan Receptors - metabolism Mice Molecular Targeted Therapy Necrosis - pathology Neoplastic Stem Cells - drug effects Neoplastic Stem Cells - metabolism Protein Binding Proto-Oncogene Proteins c-mdm2 - antagonists & inhibitors Proto-Oncogene Proteins c-mdm2 - metabolism Tumor Suppressor Protein p53 - pharmacology Xenograft Model Antitumor Assays
We have tested whether the anticancer peptide, PNC-27, that kills cancer cells but not normal cells by binding to cancer cell membrane HDM-2 forming pores, kills CD44+ colon cancer stem cells. Flow cytometry determined the CD44 and HDM-2 expression on six-colon cancer cell lines and one normal cell line (CCD-18Co). MTT, LDH release, annexin V binding and caspase 3 assays were used to assess PNC-27-induced cell death. Bioluminescence imaging measured PNC-27 effects on in vivo tumor growth. High percentages of cells in all six tumor lines expressed CD44. PNC-27 co-localized with membrane HDM-2 only in the cancer cells and caused total cell death (tumor cell necrosis, high LDH release, negative annexin V and caspase 3). In vivo, PNC-27 caused necrosis of tumor nodules but not of normal tissue. PNC-27 selectively kills colon cancer stem cells by binding of this peptide to membrane H/MDM-2.

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#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
Web of Science research areas
Oncology
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