Sreelekha T.T., Manu M. Joseph and Manojkumar T.K.
Laboratory of Biopharmaceuticals, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram-695 011, Kerala, India
Galactoxyloglucan (PST001), isolated from seed kernel of Tamarindus indica is a non-toxic antitumor and immunomodulatory compound. Toxicity associated with the chemotherapeutic drug doxorubicin (Dox) is the major impediment in its application in therapy. Spherical and stable PST-Dox nanoparticles with an average size of 10 nm were prepared via ionic gelation of Dox with PST001 which displayed a pH dependent cumulative Dox release kinetics. PST-Dox nanoparticles demonstrated cancer-specific enhanced cytotoxic effects than PST001 and Dox in cancer cell lines by enhanced cellular uptake of Dox through the induction of apoptosis, sparing normal cells, lymphocytes and RBCs. Elucidation of molecular mechanism by whole genome microarray revealed down-regulation of tyrosine kinase oncogenic pathways as PST-Dox mode of action, which was confirmed with western-blotting. An in silico model of PST- Dox was developed and computed the activity against 3QX3 (Topoisomerase IIß), 3cs9 (Human Abl kinase) and 3QRJ (protein thyrosine kinases). Computational study further confirmed the findings of genomic and proteomic analyses. To conclude, PST-Dox nanoparticles represent a superior drug delivery nanosystem for the effective treatment of cancer.