Cellular Death & Stress Responses | Cancer Therapeutics | Molecular Pharmacology | Oncology Agents | Thyroid
cAMP analogs as potential therapeutic agents for poorly differentiated thyroid cancer
Elisa Stellaria Grassi*, Alessandra Dicitore, Maria Orietta Borghi, Tiziana de Filippis, Giovanni Vitale, Luca Persani
*Corresponding author: Elisa Stellaria Grassi
Dipartimento di Scienze Mediche, Università degli Studi di Milano, Milano, Italy
F1000Posters 2012, 3: 532 (poster) [English]
Poster [5.77 MB] | Recommended by F1000Prime
Presented at
Joint 15th International Congress of Endocrinology and 14th European Congress of Endocrinology (ICE/ECE) 2012,
5 - 9 May 2012, P1752
Poorly differentiated thyroid carcinomas (PDTCs) are associated with poor prognosis and scarce response to currently available therapies (1-2).
Site-selective cAMP analogs are synthetic substances that are able to inhibit the growth of poorly differentiated solid tumors and may represent valuable candidates for the therapy of PDTCs (3-4).
We evaluated the effects of a PKA I-selective association of 8-HA-cAMP and 8-PIP-cAMP (HA:PIP) (5-6) and another analog, 8-Cl-cAMP, (7-8) on a panel of 6 cell lines from papillary, follicular, poorly differentiated and anaplastic thyroid cancer.
Our results show that 8-Cl-cAMP is able to induce modifications in cell cycle progression and cause cell death by apoptosis, while the association of 8-HA-cAMP and 8-PIP-cAMP acts in a cytostatic way by the regulation of signaling pathways involved in cell proliferation, as shown by Akt and ERK1/2 involvement.
8-Cl-cAMP may represent a powerful broad-spectrum, pro-apoptotic anticancer drug, while PKA I-selective analogs seem to preferentially inhibit undifferentiated cancer cell growth. These studies prompt further in vivo experimentation to test the efficacy and safety of these agents.
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No relevant competing interests disclosed.
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