Publication detail

Doxorubicin and ellipticine loaded apoferritin and its effect on cancer and healthy cell lines

ČERNÁ, T. HRABĚTA, J. INDRA, R. HEGER, Z. ADAM, V. ECKSCHLAGER, T. STIBOROVÁ, M.

Original Title

Doxorubicin and ellipticine loaded apoferritin and its effect on cancer and healthy cell lines

Type

presentation, poster

Language

English

Original Abstract

Despite advances in cancer diagnosis and therapy, high-risk neuroblastoma (NBL) remains lethal in about 50% of patients because of aggressive cell growth and chemoresistance. Therefore, new agents are needed to improve its prognosis. Apoferritin is a protein composed of 24 polypeptide subunits, structurally arranged to create an internal cavity, which can be artificially employed for carrying of some molecules of interest. The aim of this study was to compare the cytotoxic effects of doxorubicin (DOX) and ellipticine (ELLI) loaded apoferritin (APODOX resp. APOELLI) and free DOX resp. ELLI on NBL cells UKF-NB-4, chemoresistant sublines derived from this cell line and non-malignant fibroblasts (HDFn) in vitro. We show here that the effect of APODOX on NBL cells is similar to that of free DOX. The cytotoxicity of APOELLI is lower than cytotoxicity of free cytostatic, but APOELLI induces more double strand breaks than free ELLI. Further, using fluorescence microscopy, we have shown that apoferritin can deliver drugs inside cancer cells and the drug exerts their effect thereof. Entry of APODOX and free DOX into cancer cells was similar. However, entry of APOELLI was significantly lower than entry of free ELLI. The extent of APOELLI enter correlated with formation of covalent ELLIderived DNA adducts in tested cells; the levels of ELLI-DNA adducts generated by APOELLI were 67% of those formed by free ELLI. The results found in this study seem to be promising, because encapsulation does not affect toxicity of cytostatic and improves drug stability. Moreover, cytotoxicity of drug loaded apoferritin is significantly lower for non-malignant cells than for cancer cells. In addition, apoferritin loaded DOX and ELLI are cytotoxic in hypoxic conditions (1% O2). We suppose that apoferritin is targeted to the several cancer cells including NBL through TfR 1 and/or SCARA 5 which are expressed in many cancer cells.

Keywords

Doxorubicin; apoferritin; cancer

Authors

ČERNÁ, T.; HRABĚTA, J.; INDRA, R.; HEGER, Z.; ADAM, V.; ECKSCHLAGER, T.; STIBOROVÁ, M.

Released

31. 7. 2018

Pages from

350

Pages to

350

Pages count

1

URL

https://doi.org/10.1002/2211-5463.12453

BibTex

@misc{BUT163415,
  author="ČERNÁ, T. and HRABĚTA, J. and INDRA, R. and HEGER, Z. and ADAM, V. and ECKSCHLAGER, T. and STIBOROVÁ, M.",
  title="Doxorubicin and ellipticine loaded apoferritin and its effect on cancer and healthy cell lines
",
  year="2018",
  pages="350--350",
  url="https://doi.org/10.1002/2211-5463.12453",
  note="presentation, poster"
}