Anticancer activity of galactoxyloglucan polysaccharide-conjugated doxorubicin nanoparticles: Mechanistic insights and interactome analysis
Authors: Suraj K George
S Mini
T T Sreelekha
S R Aravind
K Raveendran Pillai
Manu M Joseph
Journal: European Journal of Pharmaceutics and Biopharmaceutics (2015)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Chemotherapy; Doxorubicin; Galactoxyloglucan nanoparticles; PST-Dox; Toxicity.
Affiliations: Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, Kerala 695011, India., Department of Hematopathology, UT MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA., Department of Pathology, Regional Cancer Centre, Thiruvananthapuram, Kerala 695011, India., Department of Biochemistry, University of Kerala, Thiruvananthapuram, Kerala 695011, India., Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, Kerala 695011, India. Electronic address: .

Abstract:  Toxicity associated with chemotherapeutic drugs such as doxorubicin (Dox), is one of the major obstacles that is currently affecting patients. PST-Dox (Galactoxyloglucan, PST001-conjugated Dox) nanoparticles were synthesized by encapsulating Dox with polysaccharide PST001, isolated from Tamarindus indica (Ti) by ionic gelation with tripolyphosphate (TPP). Herein, we demonstrate a detailed mechanistic and interactome network analysis that is specific to PST-Dox action in cancer cells and normal lymphocytes. Our results show that PST-Dox is superior to its parental counterparts, exhibiting a greater cytotoxicity by the induction of apoptosis against a wide variety of cancers by enhanced cellular uptake of Dox from the nanoparticle conjugates. Also, PST-Dox nanoparticles were non-toxic to normal lymphocytes with limited immunostimulatory effects up to certain doses. Elucidation of molecular mechanism by whole genome microarray in cancer cells and lymphocytes revealed that a large number of genes were dysregulated specifically in cancer cells. Specifically, a unique target gene EGR1, contextually determined translational activation of P53 in the cancerous and non-cancerous cells. Most of the key downregulated genes were tyrosine kinases, indicating the potential inhibitory action of PST-Dox on tyrosine kinase oncogenic pathways. Western blotting of proteins corresponding to the genes that were altered at the genomic level was very well correlated in the majority of them, except in a few that demonstrated post-transcriptional modifications. The important findings and highly disciplined approaches highlighted in the present study will speed up the therapeutic potential of this augmented nanoparticle formulation for more robust clinical studies and testing in several cancers. 

Retracted: No

PubPeer comments:
 There also appears to be some common images and overlaps between images in Figure 3e of this paper and another paper: Figure 2f, Molecular Cancer (2020), doi: 10.1186 s12943-020-1145-5 (with some common authors). I hope this illustration isn t too busy. It includes a PLoS ONE paper not involved here. *** ![file] , 
 There appears to be an image in Figure 1g of this paper that is unexpectedly similar to one in Figure 5A of the previously mentioned and now-retracted PLoS ONE (2014) paper, doi: 10.1371 journal.pone.0090952, discussed here: https: pubpeer.com publications 221B5706708AA9DDC0D30BD47A2EF6. *** ![file] *** This study is supported by National Science Foundation of China(81702557, 81860101); Hainan provincial health fund(02A2150014P1). ,