Effects of raloxifene on breast cancer cell migration and invasion through the actin cytoskeleton

Flamini, Marina Inés; Fu, Xiaodong; Sanchez, Angel Matías; Giretti, Maria Silvia; Garibaldi, Silvia; Goglia, Lorenzo; Pisaneschi, Silvia; Tosi, Veronica; Genazzani, Andrea Riccardo; Simoncini, Tommaso

doi:10.1111/j.1582-4934.2008.00505.x

Cited by 25 publications

(18 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent study shows that estradiol is able to promote breast cancer cell invasion and metastatization through RhoA/ROCK signaling [45]. Our results are in agreement with this finding, showing an estrogen-dependent RhoA/ROCKinduced regulation of epididymal cell motility.…”

Section: Discussionsupporting

confidence: 93%

Estrogens Regulate Humans and Rabbit Epididymal Contractility Through the RhoA/Rho-kinase Pathway

Fibbi¹,

Filippi²,

Morelli³

et al. 2009

The Journal of Sexual Medicine

View full text Add to dashboard Cite

Introduction We have previously demonstrated that oxytocin (OT) and endothelin-1 (ET-1) peripherally regulate epididymal motility in an estrogen-dependent way. Because RhoA/Rho-kinase (ROCK) pathway is a contractile effector downstream to both OT and ET-1 receptors, we hypothesized an estrogenic modulation of OT- and ET-1-induced contraction through the up-regulation of RhoA/ROCK signaling. Aim To evaluate the effect of changing endocrine milieu on RhoA/ROCK pathway in the epididymis. Methods We induced a pharmacological hypogonadotropic hypogonadism in rabbits and replaced hypogonadal animals with different sex steroids (testosterone, T, or estradiol valerate, [E2v]). Effects of estrogen deprivation were also evaluated in rabbits chronically treated with the P450-aromatase inhibitor letrozole. An “in vitro” model of human epididymal smooth muscle cells was established and stimulated with sex hormones (72 hours). Protein and mRNA expression and functional activity of RhoA/ROCK signaling were studied by quantitative reverse transcriptase-polymerase chain reaction, immunohistochemistry, western blot analysis, cell migration and by “in vitro” contractility studies using the ROCK inhibitor Y-27632. Main Outcome Measures Effects of sex steroids on expression and functional activation of RhoA/ROCK signaling in rabbit epididymis and human epididymal smooth muscle cells. Results The relaxant effect of Y-27632 on ET-1-pre-contracted epididymal strips was significantly reduced in hypogonadal rabbits, as well as in letrozole-treated animals. T supplementation normalized T plasma levels, but not Y-27632 epididymal strip sensitivity. E2v not only completely restored Y-27632 responsiveness but even amplified it, indicating an estrogenic up-regulation of RhoA/ROCK pathway. Accordingly, ROCK1 protein and gene expressions were strongly induced by E2v but not by T. The estrogen-induced up-regulation of RhoA/ROCK signaling was confirmed in human epididymal smooth muscle cells. Conclusions Our results suggest that estrogens regulate epididymal motility by increasing RhoA/ROCK signaling, and therefore calcium sensitivity, which tunes up responsiveness to contractile factors.

show abstract

Section: Discussionsupporting

confidence: 93%

Estrogens Regulate Humans and Rabbit Epididymal Contractility Through the RhoA/Rho-kinase Pathway

Fibbi¹,

Filippi²,

Morelli³

et al. 2009

The Journal of Sexual Medicine

View full text Add to dashboard Cite

show abstract

“…Numerous studies have confirmed that actin cytoskeleton remodeling is the basis for tumor cell migration, adhesion, and invasion272829, and a variety of molecules are involved in the regulation of actin polymerization and depolymerization, of which the LIMK gene is an important molecule3031. LIMK1 is overexpressed in a variety of malignancies including prostate, gastric, and lung cancers, and significantly promotes tumor cell invasion and metastasis323334.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of LIMK1–ADF/cofilin by DADS inhibits the migration and invasion of colon cancer

Zhou

Pan

et al. 2017

Sci Rep

View full text Add to dashboard Cite

This study aimed to explore whether the downregulation of LIM kinase 1 (LIMK1)-actin depolymerization factor (ADF, also known as destrin)/cofilin by diallyl disulfide (DADS) inhibited the migration and invasion of colon cancer. Previous studies have shown that silencing LIMK1 could significantly enhance the inhibitory effect of DADS on colon cancer cell migration and invasion, suggesting that LIMK1 was a target molecule of DADS, which needed further confirmation. This study reported that LIMK1 and destrin were highly expressed in colon cancer and associated with poor prognosis of patients with colon cancer. Also, the expression of LIMK1 was positively correlated with the expression of destrin. The overexpression of LIMK1 significantly promoted colon cancer cell migration and invasion. DADS obviously inhibited migration and invasion by suppressing the phosphorylation of ADF/cofilin via downregulation of LIMK1 in colon cancer cells. Furthermore, DADS-induced suppression of cell proliferation was enhanced and antagonized by the knockdown and overexpression of LIMK1 in vitro and in vivo, respectively. Similar results were observed for DADS-induced changes in the expression of vimentin, CD34, Ki-67, and E-cadherin in xenografted tumors. These results indicated that LIMK1 was a potential target molecule for the inhibitory effect of DADS on colon cancer cell migration and invasion.

show abstract

“…The study performed by Elizabeth et al. evaluated the effects of various combinations of raloxifene, 5‐fluorouracil, and methotrexate to determine the most effective antitumor drugs combination in bone marrow and breast cancer cells . Their results indicated that late raloxifene administration (following treatment with 5‐FU/methotrexate) provides a cytotoxic advantage against breast cancer cells as bone marrow cells are protected by 5‐FU/methotrexate.…”

Section: Discussionmentioning

confidence: 99%

Enhanced cytotoxicity and apoptosis by raloxifene in combination with estrogen and methotrexate in human endometrial stromal cells

et al. 2017

View full text Add to dashboard Cite

Endometrial hyperplasia is a condition that may lead to the development of endometrial carcinoma. Initially, changes of the endometrium are caused by the estrogen's hyperstimulation that may lead to the development of an irregular bleeding and the infertility problems. Therapy of endometrial hyperplasia is limited to medical and surgical approaches. During the past decade, the new types of drugs were developed for the treatment of the endometrial hyperplasia. Here, for the first time, we investigated the cytotoxic effects of the various combinations of estrogen, raloxifene, and methotrexate in human ThESC cell line as a possible potential treatment of the endometrial hyperplasia. Our aim was to investigate and to determine the most efficient combination of investigated drugs in ThESC cells during 24-hr period using MTT assay, FACS analysis, and immunofluorescence staining. Our results demonstrated that the combination of raloxifene with methotrexate efficiently induced both the cytotoxicity and apoptosis in ThESC cells when compared to their single effect, as well as to the effect of combined treatment of raloxifene with estrogen. The application of the low doses of methotrexate combined with raloxifene offers all advantages of a potential beneficial antitumor match in cancer chemoprevention and therapy.

show abstract

Effects of raloxifene on breast cancer cell migration and invasion through the actin cytoskeleton

Cited by 25 publications

References 28 publications

Estrogens Regulate Humans and Rabbit Epididymal Contractility Through the RhoA/Rho-kinase Pathway

Estrogens Regulate Humans and Rabbit Epididymal Contractility Through the RhoA/Rho-kinase Pathway

Downregulation of LIMK1–ADF/cofilin by DADS inhibits the migration and invasion of colon cancer

Enhanced cytotoxicity and apoptosis by raloxifene in combination with estrogen and methotrexate in human endometrial stromal cells

Contact Info

Product

Resources

About