Low sodium and tolvaptan have opposite effects in human small cell lung cancer cells

Marroncini, G.; Anceschi, Cecilia; Naldi, Laura; Fibbi, Benedetta; Baldanzi, F.; Martinelli, Serena; Polvani, S.; Maggi, Mario; Peri, Alessandro

doi:10.1016/j.mce.2021.111419

Cited by 13 publications

(26 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast with the observation that the invasiveness of cancer cells is amplified in low extracellular [Na + ] [ 27 , 39 ], and in agreement with previous observations in small cell lung cancer H69 cells [ 39 ], tolvaptan blunted the ability of HCT-8, HepG2 and SK-N-AS cells to cross matrigel-coated membranes (Fig. 7 A).…”

Section: Resultssupporting

confidence: 92%

“…The RhoA/ROCK1-2 pathway has an important role in the regulation of cell movement via the remodeling of actin cytoskeleton. Previous evidence indicated that low extracellular [Na + ] activates this pathway [ 27 , 39 ]. In addition, we have shown that tolvaptan has an inhibitory effect in H69 cells [ 39 ].…”

Section: Resultsmentioning

confidence: 99%

“…Previous evidence indicated that low extracellular [Na + ] activates this pathway [ 27 , 39 ]. In addition, we have shown that tolvaptan has an inhibitory effect in H69 cells [ 39 ].…”

Section: Resultsmentioning

confidence: 99%

“…All the reagents for cell culture were purchased from Sigma Chemical Co. (St. Louis, MO, USA). To analyse the effects of tolvaptan, cells were cultured in DMEM or RPMI medium for 48 h before experiments were performed, as previously described [ 39 ].…”

Section: Methodsmentioning

confidence: 99%

“…Noteworthy, in vitro studies have shown that tolvaptan reduces proliferation and invasion in hepatocarcinoma and renal carcinoma cells [ 37 , 38 ]. Furthermore, very recently we have demonstrated that in small-cell lung cancer cells tolvaptan counteracts cell proliferation and invasivity, yet triggers apoptosis, mainly via the inhibition of the RhoA/ROCK pathway [ 39 ].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

The V2 receptor antagonist tolvaptan counteracts proliferation and invasivity in human cancer cells

Marroncini

Anceschi

Naldi

et al. 2022

J Endocrinol Invest

View full text Add to dashboard Cite

Purpose Hyponatremia, the most frequent electrolyte alteration in clinical practice, has been associated with a worse prognosis in cancer patients. On the other hand, a better outcome has been related to serum sodium normalization. In vitro studies have shown that low extracellular sodium promotes cancer cells proliferation and invasiveness. Tolvaptan, a selective vasopressin receptor type 2 (V2) antagonist, has been effectively used in the last decade for the treatment of hyponatremia secondary to the Syndrome of Inappropriate Antidiuresis. A few in vitro data suggested a direct role of tolvaptan in counteracting cancer progression, so far. The aim of this study was to evaluate the effect and the mechanism of action of tolvaptan in cell lines from different tumours [i.e. colon cancer (HCT-8), hepatocarcinoma (HepG2), neuroblastoma (SK-N-AS)]. Methods and results First, we showed that these cell lines express the V2 receptor. Tolvaptan significantly reduced cell proliferation with an IC50 in the micromolar range. Accordingly, reduced levels of cAMP, of the catalytic α subunit of PKA, and a reduced pAKT/AKT ratio were observed. Tolvaptan effectively inhibited cell cycle progression, whereas it induced apoptotis. Furthermore, it reduced cell invasiveness. In particular, anchorage-independent growth and the activity of collagenases type IV were blunted in the three cell lines. Accordingly, tolvaptan counteracted the RhoA/ROCK1–2 pathway, which has a pivotal role in regulating cell movement. Conclusions Overall, these findings indicate that tolvaptan effectively inhibits tumour progression in vitro. Further studies should clarify whether the V2 receptor might be considered a possible target in anti-cancer strategies in the future.

show abstract

Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

“…Previous evidence indicated that low extracellular [Na + ] activates this pathway [ 27 , 39 ]. In addition, we have shown that tolvaptan has an inhibitory effect in H69 cells [ 39 ].…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The V2 receptor antagonist tolvaptan counteracts proliferation and invasivity in human cancer cells

Marroncini

Anceschi

Naldi

et al. 2022

J Endocrinol Invest

View full text Add to dashboard Cite

show abstract

Hyponatremia-related liver steatofibrosis and impaired spermatogenesis: evidence from a mouse model of the syndrome of inappropriate antidiuresis

Marroncini

Anceschi

Naldi

et al. 2022

J Endocrinol Invest

View full text Add to dashboard Cite

Purpose Hyponatremia is the most frequent electrolytic disorder in clinical practice. In addition to neurological symptoms, hyponatremia, even when mild/moderate and chronic, has been related to other manifestations, such as bone demineralization and increased risk of fractures. To better elucidate tissue alterations associated with reduced serum sodium concentration [Na+], we developed an in vivo model of hyponatremia secondary to the Syndrome of Inappropriate Antidiuresis. Methods and results Hyponatremia was induced in Foxn1nu/nu mice by subcutaneous infusion of the vasopressin analog 1-deamino [8-D-arginine] vasopressin (dDAVP) for 14 days via osmotic mini-pumps. Mice in the control group were infused with isotonic saline solution. Serum [Na+] progressively decreased, with a nadir of 123.4 ± 2.3 mEq/L (mean ± SD, dDAVP 0.3 ng/h) and 111.6 ± 4.7 mEq/L (mean ± SD, dDAVP 0.5 ng/h). Evident signs of liver steatofibrosis were observed at histology in hyponatremic mice. Accordingly, the expression of proteins involved in lipid metabolism (SREBP-1, PPARα and PPARγ) and in myofibroblast formation (αSMA and CTGF) significantly increased. Furthermore, heme oxygenase 1 expression was up-regulated in Kupffer and hepatic stellate cells in the liver of hyponatremic mice. Testis alterations were also observed. In particular, the thickness of the seminiferous epithelium appeared reduced. The expression levels of PCNA and PTMA, which are involved in DNA replication and germ cells maturation, were markedly reduced in the testis of hyponatremic mice. Conclusion Overall, these findings shed new light on the possible consequences of chronic hyponatremia and prompt a more thorough evaluation of hyponatremic patients.

show abstract

Hyponatremia elicits gene expression changes driving osteoclast differentiation and functions

Barsony

Verbalis

2022

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

Low sodium and tolvaptan have opposite effects in human small cell lung cancer cells

Cited by 13 publications

References 53 publications

The V2 receptor antagonist tolvaptan counteracts proliferation and invasivity in human cancer cells

The V2 receptor antagonist tolvaptan counteracts proliferation and invasivity in human cancer cells

Hyponatremia-related liver steatofibrosis and impaired spermatogenesis: evidence from a mouse model of the syndrome of inappropriate antidiuresis

Hyponatremia elicits gene expression changes driving osteoclast differentiation and functions

Contact Info

Product

Resources

About