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Pregled bibliografske jedinice broj: 507979

Inhibition of ovarian cancer cell proliferation by a cell cycle inhibitory peptide fused to a thermally responsive polypeptide carrier


Massodi, Iqbal; Moktan, Shama; Rawat, Aruna; Bidwell, Gene Lee III.; Raucher, Dražen
Inhibition of ovarian cancer cell proliferation by a cell cycle inhibitory peptide fused to a thermally responsive polypeptide carrier // International journal of cancer, 126 (2010), 2; 533-544 doi:10.1002/ijc.24725 (međunarodna recenzija, članak, znanstveni)


Naslov
Inhibition of ovarian cancer cell proliferation by a cell cycle inhibitory peptide fused to a thermally responsive polypeptide carrier

Autori
Massodi, Iqbal ; Moktan, Shama ; Rawat, Aruna ; Bidwell, Gene Lee III. ; Raucher, Dražen

Izvornik
International journal of cancer (0020-7136) 126 (2010), 2; 533-544

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Drug delivery; thermal targeting; cell cycle inhibition

Sažetak
Current treatment of solid tumors is limited by normal tissue tolerance, resulting in a narrow therapeutic index. To increase drug specificity and efficacy and to reduce toxicity in normal tissues, we have developed a polypeptide carrier for a cell cycle inhibitory peptide, which has the potential to be thermally targeted to the tumor site. The design of this polypeptide is based on elastin-like polypeptide (ELP). The coding sequence of ELP was modified by the addition of the cell penetrating peptide Bac-7 at the N-terminus and a 23 amino acid peptide derived from p21 at the C-terminus (Bac-ELP1-p21). Bac-ELP1-p21 is soluble in aqueous solutions below physiological temperature (37 degrees C) but aggregates when the temperature is raised above 39 degrees C, making it a promising thermally responsive therapeutic carrier that may be actively targeted to solid tumors by application of focused hyperthermia. While Bac-ELP1-p21 at 37 degrees C did not have any effect on SKOV-3 cell proliferation, the use of hyperthermia increased the antiproliferative effect of Bac-ELP1-p21 compared with a thermally unresponsive control polypeptide. Bac-ELP1-p21 displayed both a cytoplasmic and nuclear distribution in the SKOV-3 cells, with nuclear-localized polypeptide enriched in the heated cells, as revealed by confocal microscopy. Using Western blotting, we show that Bac-ELP1-p21 caused a decrease in Rb phosphorylation levels in cells treated at 42 degrees C. The polypeptide also induced caspase activation, PARP cleavage, and cell cycle arrest in S-phase and G2/M-phase. These studies indicate that ELP is a promising macromolecular carrier for the delivery of cell cycle inhibitory peptides to solid tumors

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
219-0000000-3364 - Ciljano toplinsko dopremanje lijekova u solidne tumore (Dražen Raucher, )

Ustanove
Medicinski fakultet, Osijek

Autor s matičnim brojem:
Dražen Raucher, (280455)

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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