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Nano‐formulation Enhances the Anti‐angiogenic Potential of Tunicamycin
Author(s) -
Banerjee Dipak,
Banerjee Aditi,
Seijo Arelis,
Serrano Jesus,
Perez Linyer,
Linares Lorraine,
Ramos Mariela,
Baksi Krishna
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.897.11
Subject(s) - tunicamycin , angiogenesis , cancer research , cyclin d1 , unfolded protein response , cancer , matrigel , cell growth , in vivo , chemistry , cell cycle , biology , medicine , apoptosis , biochemistry , microbiology and biotechnology
Breast cancer is characterized by the progressive accumulation of mutations and chromosomal aberrations leading to altered growth properties and oncogenic transformations of cells. Both endogenous and exogenous factors contribute. Current understanding on the blood vessel formation has developed therapies to interrupt the angiogenic process. But, due to poor performance and inefficacy, many anti‐angiogenic/anti‐cancer treatments have been called into question. After achieving a success with tunicamycin (a biologic) in inhibiting angiogenesis in vitro and in vivo (Matrigel™ implants in nude mice) and consequently the prevention of breast tumor progression ~55‐65% in 3 weeks in athymic nude mice we have developed a nano‐formulation to increase efficacy. Tunicamycin gold nano‐particles inhibited cellular proliferation ~50% (MTT assay) within one hour of treatment. Cell cycle progression was blocked due to inhibition of either both cyclin D1 and cdk4, or cyclin D1, or the cdk4 expression as well as the expression of phospho Rb. Phosphorylation of p53 (serine‐392) was also down‐regulated. Increased expression of GRP‐78/Bip identified “ER stress”. Upregulated expression (1.6‐5.5 folds) of phospho‐PERK supported induction of unfolded protein response ( upr ) signaling but no apoptosis. Supported in part by grants from Susan G. Komen for Cure BCTR0600582 (DKB) and NIH/NIMHD 2G12MD007583 (KB).