The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy

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Authors

MILOSAVLJEVIC Vedran HADDAD Yazan RODRIGO Miguel Angel Merlos MOULICK Amitava POLANSKÁ Hana HYNEK David HEGER Zbynek KOPEL Pavel ADAM Vojtech

Year of publication 2016
Type Article in Periodical
Magazine / Source Plos one
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1371/journal.pone.0163983
Field Oncology and hematology
Keywords TRANSCRIPTION FACTOR SP1; STEADY-STATE; CELL-LINES; EXPRESSION; APOPTOSIS; ACTIVATION; MICROARRAY; PROTEIN; MODEL; P53
Description Prostate cancer cells control energy metabolism by chelating intracellular zinc. Thus, zinc delivery has been a popular therapeutic approach for prostate cancer. Here, we propose the use of the membrane-penetrating peptide Novicidin connected to zinc-Schiff base as a carrier vehicle for the delivery of zinc to prostate cells. Mass spectrometry, electrochemistry and spectrophotometry confirmed the formation/stability of this complex and provided insight regarding the availability of zinc for complex interactions. This delivery system showed minor toxicity in normal PNT1A cells and high potency towards PC3 tumor cells. The complex preferentially penetrated PC3 tumor cells in contrast to confinement to the membranes of PNT1A. Furthermore, zinc uptake was confirmed in both cell lines. Molecular analysis was used to confirm the activation of zinc stress (e.g., ZnT-1) and apoptosis (e.g., CASP-1). Our results strongly suggest that the zinc-Schiff base-Novicidin complex has great potential as a novel anticancer drug.
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