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Thadi A , Morano WF , Khalili M , Babcock BD , Shaikh MF , Foster DS , Piazza Y , Gleeson EM , Goldstein E , Steele L , Campbell PM , Lin BO , Pincus MR , Bowne WB
Molecular Targeting of H/MDM-2 Oncoprotein in Human Colon Cancer Cells and Stem-like Colonic Epithelial-derived Progenitor Cells
Anticancer Res. 2021 Jan;41(1) :27-42
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Abstract
BACKGROUND/AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: PNC-27 selectively kills colon cancer stem cells by binding of this peptide to membrane H/MDM-2.
Notes
1791-7530 Thadi, Anusha Morano, William F Khalili, Marian Babcock, Blake D Shaikh, Mohammad F Foster, Deshka S Piazza, Yelena Gleeson, Elizabeth M Goldstein, Eve Steele, Lindsay Campbell, Paul M Lin, B O Pincus, Matthew R Bowne, Wilbur B Journal Article Greece Anticancer Res. 2021 Jan;41(1):27-42. doi: 10.21873/anticanres.14749.