Effects of sorafenib and an adenylyl cyclase activator on &lt;i&gt;in vitro&lt;/i&gt; growth of well-differentiated thyroid cancer cells

Sawa, Aya; Chiba, Tomohiro; Ishii, Jun; Yamamoto, Hiroyuki; Hara, Hisato; Kamma, Hiroshi

doi:10.1507/endocrj.ej16-0525

“…More recently, a study compared sorafenib and forskolin, an adenylyl cyclase activator, in in vitro models of 3 human DTC cell lines (TPC-1, KTC1, and WRO) [118].…”

Section: Sorafenibmentioning

confidence: 99%

Primary cell cultures for the personalized therapy in aggressive thyroid cancer of follicular origin

Fallahi

¹

,

Ferrari

²

,

Elia

³

et al. 2022

Seminars in Cancer Biology

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“…This incongruity can be explained by two theories on the cAMP signalling cascade. The first theory proposes that elevation of intracellular cAMP is beneficial for suppressing cell proliferation in most mesenchymal and epithelial cell lines, such as glioblastoma (Kang et al 2014), thyroid cells (Sawa et al 2017), lung and breast carcinoma cells (Lerner and Epstein 2006), ovarian granulosa cells (Zwain and Amato 2001), fibroblasts (Huston et al 2006), and primary cardiomyocytes (Ding et al 2005). In contrast, the second theory proposes that cAMP promotes cell survival, which has been observed in myeloid cells, pancreatic -cells, hepatocytes, gastric and intestinal cells, spinal motor, superior cervical ganglion sympathetic, dorsal root ganglion, dopaminergic neurons, cerebral granule and septal cholinergic neurons (Kwon et al 2004, Lerner and Epstein 2006, Cullen et al 2004, Nishihara et al 2003, Hoshino et al 2003, Chin and D'Mello 2005.…”

Section: Introductionmentioning

confidence: 99%

Elevated intracellular cAMP concentration mediates growth suppression in glioma cells

Safitri

¹

,

Potter

²

,

Harris

³

et al. 2019

Preprint

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Supressed levels of intracellular cAMP have been associated with malignancy. Thus, elevating cAMP through activation of adenylyl cyclase (AC) or by inhibition of phosphodiesterase (PDE) may be therapeutically beneficial. Here, we demonstrate that elevated cAMP levels suppress growth in C6 cells (a model of glioma) through treatment with forskolin, an AC activator, or a range of small molecule PDE inhibitors with differing selectivity profiles. Forskolin suppressed cell growth in a protein kinase A (PKA)-dependent manner by inducing a G2/M phase cell cycle arrest. In contrast, trequinsin (a non-selective PDE2/3/7 inhibitor), not only inhibited cell growth via PKA, but also stimulated (independent of PKA) caspase-3/-7 and induced an aneuploidy phenotype. Interestingly, a cocktail of individual PDE 2,3,7 inhibitors suppressed cell growth in a manner analogous to forskolin but not trequinsin.Finally, we demonstrate that concomitant targeting of both AC and PDEs synergistically elevated intracellular cAMP levels thereby potentiating their antiproliferative actions.

show abstract

Elevated intracellular cAMP concentration mediates growth suppression in glioma cells

Safitri

¹

,

Harris

²

,

Potter

³

et al. 2020

Biochemical Pharmacology

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Supressed levels of intracellular cAMP have been associated with malignancy. Thus, elevating cAMP through activation of adenylyl cyclase (AC) or by inhibition of phosphodiesterase (PDE) may be therapeutically beneficial. Here, we demonstrate that elevated cAMP levels suppress growth in C6 cells (a model of glioma) through treatment with forskolin, an AC activator, or a range of small molecule PDE inhibitors with differing selectivity profiles. Forskolin suppressed cell growth in a protein kinase A (PKA)-dependent manner by inducing a G2/M phase cell cycle arrest. In contrast, trequinsin (a non-selective PDE2/3/7 inhibitor), not only inhibited cell growth via PKA, but also stimulated (independent of PKA) caspase-3/-7 and induced an aneuploidy phenotype. Interestingly, a cocktail of individual PDE 2,3,7 inhibitors suppressed cell growth in a manner analogous to forskolin but not trequinsin.Finally, we demonstrate that concomitant targeting of both AC and PDEs synergistically elevated intracellular cAMP levels thereby potentiating their antiproliferative actions.

show abstract

Effects of sorafenib and an adenylyl cyclase activator on <i>in vitro</i> growth of well-differentiated thyroid cancer cells

Cited by 4 publications

References 26 publications

Primary cell cultures for the personalized therapy in aggressive thyroid cancer of follicular origin

Primary cell cultures for the personalized therapy in aggressive thyroid cancer of follicular origin

Elevated intracellular cAMP concentration mediates growth suppression in glioma cells

Elevated intracellular cAMP concentration mediates growth suppression in glioma cells

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