Tetraiodothyroacetic acid (tetrac) and nanoparticulate tetrac arrest growth of medullary carcinoma of the thyroid.
BACKGROUND
Tetraiodothyroacetic acid (tetrac) blocks angiogenic and tumor cell proliferation actions of thyroid hormone initiated at the cell surface hormone receptor on integrin alphavbeta3. Tetrac also inhibits angiogenesis initiated by vascular endothelial growth factor and basic fibroblast growth factor.


OBJECTIVE
We tested antiangiogenic and antiproliferative efficacy of tetrac and tetrac nanoparticles (tetrac NP) against human medullary thyroid carcinoma (h-MTC) implants in the chick chorioallantoic membrane (CAM) and h-MTC xenografts in the nude mouse.


METHODS
h-MTC cells were implanted in the CAM model (n = 8 per group); effects of tetrac and tetrac NP at 1 microg/CAM were determined on tumor angiogenesis and tumor growth after 8 d. h-MTC cells were also implanted sc in nude mice (n = 6 animals per group), and actions on established tumor growth of unmodified tetrac and tetrac NP ip were determined.


RESULTS
In the CAM, tetrac and tetrac NP inhibited tumor growth and tumor-associated angiogenesis. In the nude mouse xenograft model, established 450-500 mm(3) h-MTC tumors were reduced in size over 21 d by both tetrac formulations to less than the initial cell mass (100 mm(3)). Tumor tissue hemoglobin content of xenografts decreased by 66% over the course of administration of each drug. RNA microarray and quantitative real-time PCR of tumor cell mRNAs revealed that both tetrac formulations significantly induced antiangiogenic thrombospondin 1 and apoptosis activator gene expression.


CONCLUSIONS
Acting via a cell surface receptor, tetrac and tetrac NP inhibit growth of h-MTC cells and associated angiogenesis in CAM and mouse xenograft models.
Yalcin
M
M
The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, New York 12208, USA.
Dyskin
E
E
Lansing
L
L
Bharali
D J
DJ
Mousa
S S
SS
Bridoux
A
A
Hercbergs
A H
AH
Lin
H Y
HY
Davis
F B
FB
Glinsky
G V
GV
Glinskii
A
A
Ma
J
J
Davis
P J
PJ
Mousa
S A
SA
D000818:Animals; D000970:Antineoplastic Agents; D001835:Body Weight / Q000187:drug effects; D018276:Carcinoma, Medullary / Q000188:drug therapy* / Q000473:pathology; D002478:Cells, Cultured; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000473:pathology; D005079:Excipients; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control; D020411:Oligonucleotide Array Sequence Analysis; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013974:Thyroxine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D005079:Excipients; D006454:Hemoglobins; D012334:RNA, Neoplasm; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C011126:tetraiodothyroacetic acid; D013974:Thyroxine