Anti-Cancer Agents in Medicinal Chemistry, Year (2018-4)

Title : ( Poly-L-arginine: Enhancing Cytotoxicity and Cellular Uptake of Doxorubicin and Necrotic Cell Death )

Authors: Bahareh Movafegh , Razieh Jalal , zobeide mohammadi , Seyyede Araste Aldaghi ,

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OBJECTIVE: Cell resistance to doxorubicin and its toxicity to healthy tissue reduce its efficiency. The use of cell penetrating peptides as drug delivery system along with doxorubicin is a strategy to reduce its side effects. In this study, the influence of poly-L-arginine on doxorubicin cytotoxicity, its cellular uptake and doxorubicin-induced apoptosis on human prostate cancer DU145 cells are assessed. METHODS: The cytotoxicity of doxorubicin and poly-L-arginine, alone and in combination, in DU145 cells was evaluated at different exposure times using MTT assay. The influence of poly-L-arginine on doxorubicin delivery into cells was evaluated by fluorescence microscopy and ultraviolet spectroscopy. DAPI and ethidium bromide-acridine orange stainings, flow cytometry using annexin V/propidium iodide, western blot analysis with anti-p21 antibody and caspase-3 activity were used to examine the influence of poly-L-arginine on doxorubicin-induced cell death. RESULTS: Poly-L-arginine had no cytotoxicity at low concentrations and short exposure times. Poly-L-arginine increased the cytotoxic effect of doxorubicin in DU145 cells in a time-dependent manner. But no significant reduction was found in HFF cell viability. Poly-L-arginine seems to facilitate doxorubicin uptake and increase its intracellular concentration. 24 h combined treatment of cells with doxorubicin -0.5 μM- and poly-L-arginine -1 μg ml-1- caused a small increase in doxorubicin-induced apoptosis and significant elevated necrosis in DU145 cells as compared to each agent alone. Conlusion: Our results indicate that poly-L-arginine at lowest and highest concentrations act as proliferation-inducing and antiproliferative agents, respectively. Between these concentrations, poly-L-arginine increases the cellular uptake of doxorubicin and its cytotoxicity through induction of necrosis.


, Apoptosis; Cell penetrating peptides; Doxorubicin , DOX, ; Necrosis; Poly, L, arginine , PLA, ; Prostate cancer
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author = {Movafegh, Bahareh and Jalal, Razieh and Mohammadi, Zobeide and Aldaghi, Seyyede Araste},
title = {Poly-L-arginine: Enhancing Cytotoxicity and Cellular Uptake of Doxorubicin and Necrotic Cell Death},
journal = {Anti-Cancer Agents in Medicinal Chemistry},
year = {2018},
month = {April},
issn = {1871-5206},
keywords = {Apoptosis; Cell penetrating peptides; Doxorubicin -DOX-; Necrosis; Poly-L-arginine -PLA-; Prostate cancer},


%0 Journal Article
%T Poly-L-arginine: Enhancing Cytotoxicity and Cellular Uptake of Doxorubicin and Necrotic Cell Death
%A Movafegh, Bahareh
%A Jalal, Razieh
%A Mohammadi, Zobeide
%A Aldaghi, Seyyede Araste
%J Anti-Cancer Agents in Medicinal Chemistry
%@ 1871-5206
%D 2018