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]
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.
No relevant competing interests disclosed.
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