Openly accessible

Doxorubicin conjugated to immunomodulatory anticancer lactoferrin displays improved cytotoxicity overcoming prostate cancer chemo resistance and Inhibits tumour development in TRAMP mice

Shankara Narayanan, Jayanth Suryanarayanan, Kanwar, Jagat R., Al-Juhaishi, Afrah Jalil Abd and Kanwar, Rupinder K. 2016, Doxorubicin conjugated to immunomodulatory anticancer lactoferrin displays improved cytotoxicity overcoming prostate cancer chemo resistance and Inhibits tumour development in TRAMP mice, Scientific reports, vol. 6, Article number : 32062, pp. 1-16, doi: 10.1038/srep32062.

Attached Files
Name Description MIMEType Size Downloads
narayanan-immunomodulatory-2016.pdf Published version application/pdf 2.81MB 113

Title Doxorubicin conjugated to immunomodulatory anticancer lactoferrin displays improved cytotoxicity overcoming prostate cancer chemo resistance and Inhibits tumour development in TRAMP mice
Author(s) Shankara Narayanan, Jayanth Suryanarayanan
Kanwar, Jagat R.ORCID iD for Kanwar, Jagat R. orcid.org/0000-0003-3728-9568
Al-Juhaishi, Afrah Jalil Abd
Kanwar, Rupinder K.
Journal name Scientific reports
Volume number 6
Season Article number : 32062
Start page 1
End page 16
Total pages 16
Publisher Nature Publishing Group
Place of publication London, Eng.
Publication date 2016
ISSN 2045-2322
Keyword(s) cancer therapeutic resistance
drug delivery
prostate cancer
Summary Advanced, metastatic, castration resistant and chemo-resistant prostate cancer has triggered change in the drug development landscape against prostate cancer. Bovine lactoferrin (bLf) is currently attracting attention in clinics for its anti-cancer properties and proven safety profile. bLf internalises into cancer cells via receptor mediated endocytosis, boosts immunity and complements chemotherapy. We employed bLf as an excellent functional carrier protein for delivering doxorubicin (Dox) into DU145 cells, CD44+/EpCAM+ double positive enriched DU145 3D prostaspheres and drug resistant ADR1000-DU145 cells, thus circumventing Dox efflux, to overcome chemo-resistance. Successful bLf-Dox conjugation with iron free or iron saturated bLf forms did not affect the integrity and functionality of bLf and Dox. bLf-Dox internalised into DU145 cells within 6 h, enhanced nuclear Dox retention up to 24 h, and proved significantly effective (p < 0.001) in reducing LC50 value of Dox from 5.3 μM to 1.3 μM (4 fold). Orally fed iron saturated bLf-Dox inhibited tumour development, prolonged survival, reduced Dox induced general toxicity, cardiotoxicity, neurotoxicity in TRAMP mice and upregulated serum levels of anti-cancer molecules TNF-α, IFN-γ, CCL4 and CCL17. The study identifies promising potential of a novel and safer bLf-Dox conjugate containing a conventional cytotoxic drug along with bLf protein to target drug resistance.
Language eng
DOI 10.1038/srep32062
Field of Research 110399 Clinical Sciences not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30086444

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 16 times in TR Web of Science
Scopus Citation Count Cited 18 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 456 Abstract Views, 114 File Downloads  -  Detailed Statistics
Created: Mon, 03 Oct 2016, 13:39:56 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.