Doxorubicin Conjugated to Immunomodulatory Anticancer Lactoferrin Displays Improved Cytotoxicity Overcoming Prostate Cancer Chemo resistance and Inhibits Tumour Development in TRAMP Mice

نویسندگان

  • Jayanth Suryanarayanan Shankaranarayanan
  • Jagat R. Kanwar
  • Afrah Jalil Abd AL-Juhaishi
  • Rupinder K. Kanwar
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

ZnO nanofluids for the improved cytotoxicity and cellular uptake of doxorubicin

Objective(s): Combination anticancer therapy holds promise for improving the therapeutic efficacy of chemotherapy drugs such as doxorubicin (DOX) as well as decreasing their dose-limiting side effects. Overcoming the side effects of doxorubicin (DOX) is a major challenge to the effective treatment of cancer. Zinc oxide nanoparticles (ZnO NPs) are emerging as potent tools for a wide variety of b...

متن کامل

Anticancer activity of Doxorubicin conjugated to polymer/carbon based-nanohybrid against MCF-7 breast and HT-29 colon cancer cells

The Cancer is one of the world’s most devastating diseases. Doxorubicin (DOX) is an effective chemotherapeutic drug; however, its toxicity is a significant limitation in therapy. Due to the severe side effects of chemotherapy drugs, scientists have tried to load these drugs in nanocomposites. This paper describes a facile and low cost approach for preparation polymeric biodegradable nanohybrid ...

متن کامل

Quercetin induces cell cycle arrest and apoptosis in CD133+ cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin

Objective(s):The colorectal cancer stem cells (CSCs) with the CD133+ phenotype are a rare fraction of cancer cells with the ability of self-renewal, unlimited proliferation and resistance to treatment. Quercetin has anticancer effects with the advantage of exhibiting low side effects. Therefore, we evaluated the anticancer effects of quercetin and doxorubicin (Dox) in HT29 cancer cells and its ...

متن کامل

Investigating the effects of Sea anemone (Stichodactyla haddoni) mucus on prostate cancer PC3 cell line

Background & Aim: Prostate cancer (PCa) is one of the most common cancers of the male urinary system and is also the second leading cause of cancer deaths in men. In the present study, the effects of Stichodactyla haddoni on the viability of prostate cancer cells (PC3) were investigated. Methods: In the semi experimental study, sea anemones were sampled at random using an identification key. T...

متن کامل

Effect of Clarithromycin on Enhancement of Doxorubicin-induced Cytotoxicity and Apoptosis in A549 Tumor-Cell Line

Background and purpose: Nowadays, multi-drug regimens or combination therapy are new approaches in cancer treatment that combine two or several therapeutic agents. Combination therapy aims at improving the therapeutic efficacy of anticancer drugs while reducing toxicity and preventing drug resistance. The aim of this study was to determine the synergistic effect of combined clarithromycin and d...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2016