title: Pseudomonas aeruginosa exotoxin T induces potent cytotoxicity against a variety of murine and human cancer cell lines.
abstract: In patients with malignancy, the major barrier to achieving complete response is emergence of resistance to current chemotherapeutic agents. One of the major mechanisms by which tumour cells become resistant to therapies is by altering cellular drug targets through mutations and/or deletions. Resistance by this mechanism is achieved more easily if the drug has limited cellular targets and/or processes. We hypothesized that as Pseudomonas aeruginosa exotoxin T (ExoT) targets six proteins that are required for cancer cell survival and proliferation, it is highly unlikely for cancer cells to develop resistance to this toxin. We assessed ExoT's cytotoxicity against multiple invasive and highly resistant tumour cell lines in order to evaluate its potential as a chemotherapeutic agent. Our data demonstrated that ExoT induced potent cytotoxicity in all tumour cell lines that we examined. Collectively, our data highlighted the potential of ExoT as a possible chemotherapeutic candidate for the treatment of cancer.
authors: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL, USA.
authors: Joe
authors: J
authors: Goldufsky
authors: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL, USA.
authors: Stephen
authors: S
authors: Wood
authors: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL, USA.
authors: Behnam
authors: B
authors: Hajihossainlou
authors: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL, USA.
authors: Tooba
authors: T
authors: Rehman
authors: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL, USA.
authors: Omar
authors: O
authors: Majdobeh
authors: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
authors: Howard L
authors: HL
authors: Kaufman
authors: Department of Surgery, Rush University Medical Center, Chicago, IL, USA Sarepta Therapeutics, Corvallis, OR, USA.
authors: Carl E
authors: CE
authors: Ruby
authors: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL, USA Rush University Cancer Center, Rush University Medical Center, Chicago, IL, USA sasha_shafikhani@rush.edu.
authors: Sasha H
authors: SH
authors: Shafikhani
mesh_terms: D036002:ADP Ribose Transferases / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D005260:Female; D020690:GTPase-Activating Proteins / Q000494:pharmacology*; D006801:Humans; D051379:Mice
chemical_list: D000970:Antineoplastic Agents; C477521:ExoT protein, Pseudomonas aeruginosa; D020690:GTPase-Activating Proteins; D036002:ADP Ribose Transferases
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