A thermally responsive Tat-elastin-like polypeptide fusion protein induces membrane leakage, apoptosis, and cell death in human breast cancer cells.
The thermally responsive elastin-like polypeptide (ELP) has great potential as a macromolecular drug delivery vehicle due to its ability to be actively targeted to solid tumors by application of focused hyperthermia. Since, the toxicity properties of a new therapeutic delivery vehicle are crucial to its utility as an effective delivery vehicle, we evaluated the cytotoxicity of a thermally responsive Tat-ELP1 in various cell lines in response to hyperthermia. We report that Tat-ELP1 was not cytotoxic at 37 degrees C in SK-MEL-2, SKOV-3 and WI-38 cells, and only mildly toxic in the MCF-7 breast carcinoma cell line. Application of hyperthermia (42 degrees C) in combination with Tat-ELP1 resulted in cytotoxicity in all cell lines tested, and this toxicity was most prominent in the MCF-7 cell line, which was chosen to study the mechanism behind this increased toxicity. We found that Tat-ELP1 combined with hyperthermia caused membrane leakage and apoptosis, resulting in cell death, but no hemolytic effect was observed on murine erythrocytes.
Massodi
Iqbal
I
Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Raucher
Drazen
D
D000595:Amino Acid Sequence; D017209:Apoptosis; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D004549:Elastin / Q000737:chemistry*; D015696:Gene Products, tat / Q000737:chemistry*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry*; D013696:Temperature
D015696:Gene Products, tat; D011993:Recombinant Fusion Proteins; D004549:Elastin; D007770:L-Lactate Dehydrogenase