Journal article
Anti-Cancer Tumor Cell Necrosis of Epithelial Ovarian Cancer Cell Lines Depends on High Expression of HDM-2 Protein in Their Membranes
Annals of clinical and laboratory science, v 50(5), pp 611-624
01 Sep 2020
PMID: 33067207
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Objective. Patients with epithelial ovarian cancers experience the highest fatality rates among all gynecological malignancies which require development of novel treatment strategies. Tumor cell necrosis was previously reported in a number of cancer cell lines following treatment with a p53-derived anti-cancer peptide called PNC-27. This peptide induces necrosis by transmembrane pore formation with HDM-2 protein that is expressed in the cancer cell membrane. We aimed to extend these studies further by investigating expression of membrane HDM-2 protein in ovarian cancer as it relates to susceptibility to PNC-27. Procedures. Herein, we measured HDM-2 membrane expression in two ovarian cancer cell lines (SKOV-3 and OVCAR-3) and a non-transformed control cell line (HUVEC) by flow cytometric and western blot analysis. Immunofluorescence was used to visualize colocalization of PNC-27 with membrane HDM-2. Treatment effects with PNC-27 and control peptide were assessed using a MTT cell proliferation assay while direct cytotoxicity was measured by lactate dehydrogenase (LDH) release and induction of apoptotic markers; annexin V and caspase-3. Results. HDM-2 protein was highly expressed and frequently detected in the membranes of SKOV-3 and OVCAR-3 cells; a prominent 47.6 kDa HDM-2 plasma membrane isoform was present in both cell lines whereas 25, 29, and 30 kDa isoforms were preferentially expressed in OVCAR-3. Notably, PNC-27 colocalized with HDM-2 in the membranes of both cancer cell lines that resulted in rapid cellular necrosis. In contrast, no PNC-27 colocalization and cytotoxicity was observed with non-transformed HUVEC demonstrating minimal expression of membrane HDM-2. Conclusions. Our results suggest that HDM-2 is highly expressed in the membranes of these ovarian cancer cell lines and colocalizes with PNC-27. We therefore conclude that the association of PNC-27 with preferentially expressed membrane HDM-2 isoforms results in the proposed model for the formation of transmembrane pores and epithelial ovarian cancer tumor cell necrosis, as previously described in a number of solid tissue and hematologic malignancies.
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Details
- Title
- Anti-Cancer Tumor Cell Necrosis of Epithelial Ovarian Cancer Cell Lines Depends on High Expression of HDM-2 Protein in Their Membranes
- Creators
- Anusha Thadi - Drexel Univ, Dept Surg, Coll Med, Div Surg Oncol, Philadelphia, PA 19104 USAElizabeth M. Gleeson - Drexel Univ, Dept Surg, Coll Med, Div Surg Oncol, Philadelphia, PA 19104 USAMarian Khalili - Drexel Univ, Dept Surg, Coll Med, Div Surg Oncol, Philadelphia, PA 19104 USAMohammad F. Shaikh - Drexel Univ, Dept Surg, Coll Med, Div Surg Oncol, Philadelphia, PA 19104 USAEve Goldstein - Drexel Univ, Dept Surg, Coll Med, Div Surg Oncol, Philadelphia, PA 19104 USAWilliam F. Morano - Drexel Univ, Dept Surg, Coll Med, Div Surg Oncol, Philadelphia, PA 19104 USALynsey M. Daniels - Drexel Univ, Dept Surg, Coll Med, Div Surg Oncol, Philadelphia, PA 19104 USANikhil Grandhi - Drexel Univ, Dept Surg, Coll Med, Div Surg Oncol, Philadelphia, PA 19104 USAHaley Glatthorn - Drexel Univ, Dept Surg, Coll Med, Div Surg Oncol, Philadelphia, PA 19104 USAScott D. Richard - Jefferson Univ Hosp, Dept Gynecol Oncol, Div Obstet & Gynecol, Philadelphia, PA USAPaul M. Campbell - Fox Chase Canc Ctr, Marvin & Concetta Greenberg Pancreat Canc Inst, Canc Biol Program, 7701 Burholme Ave, Philadelphia, PA 19111 USAEhsan Sarafraz-Yazdi - NomoCan Pharmaceut LLC, New York Blood Ctr, New York, NY USAMatthew R. Pincus - Suny Downstate Med Ctr, Dept Pathol & Lab Med, Brooklyn, NY 11203 USAWilbur B. Bowne - Drexel Univ, Dept Surg, Coll Med, Div Surg Oncol, Philadelphia, PA 19104 USA
- Publication Details
- Annals of clinical and laboratory science, v 50(5), pp 611-624
- Publisher
- Assoc Clinical Scientists
- Number of pages
- 14
- Grant note
- Society of Gynecologic Oncology, Chicago IL Sidney Kimmel Cancer Center Consortium Symposium, Philadelphia PA PNC-27; PNC-29 / Drexel University College of Medicine, Department of Obstetrics and Gynecology research
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Obstetrics and Gynecology
- Web of Science ID
- WOS:000581709000006
- Scopus ID
- 2-s2.0-85093705961
- Other Identifier
- 991019167834004721
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- Domestic collaboration
- Web of Science research areas
- Medical Laboratory Technology