Icariin exterts negative effects on human gastric cancer cell invasion and migration by vasodilator-stimulated phosphoprotein via Rac1 pathway

Wang, Yongping; Dong, Hongyan; Zhu, Meng; Ou, Yangwen; Zhang, Jie; Luo, Haitao; Luo, Renshi; Wu, Junzhu; Mao, Ming; Liu, Xiaoheng; Zhang, Jingwei; Wei, Lei

doi:10.1016/j.ejphar.2010.03.017

Cited by 60 publications

(50 citation statements)

References 34 publications

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“…Inhibition of cell migration after silencing VASP in Mg-63 cells clearly suggests that VASP plays a positive role in regulating osteosarcoma cell motility. Our observations are in line with other studies carried on Listeria (33,34), macrophages (35), and several types of cancer cells (8,9,14,36,37). However, there have been reports of an opposite effect of VASP.…”

Section: Discussionsupporting

confidence: 82%

“…Mg-63 cells, which expressed higher levels of VASP, moved much faster than Saos-2 cells. Our observations are in accordance with various reports presented in the literature for other types of cancer cells (8,9,13,14). Furthermore, we silenced VASP using specific siRNA in Mg-63 cells.…”

Section: Discussionsupporting

confidence: 80%

“…Rac1 was found to be required in growth factor-(17) and integrin-mediated (18) cytoskeleton remodeling and migration. Other studies in the literature also showed that Rac1 plays a crucial role in tumor cell migration (9,13,36). Given the importance of both Rac1 and VASP in the actin-based process, we tried to determine whether there is a relationship between these two proteins.…”

Section: Discussionmentioning

confidence: 99%

“…For example, its level was found to be significantly increased in lung adenocarcinomas and gastric carcinomas compared to normal tissue, and this increase was correlated with the metastatic ability of these tumors (8,9). Depletion of VASP in breast cancer MDA-MB-231 cells resulted in decreased cell migration (13) and, conversely, enhanced VASP in breast cancer MDA-231 cells led to increased cell mobility (14).…”

Section: Introductionmentioning

confidence: 99%

“…In addition to its role in normal cell growth (4,5), embryonic development (6) and homeostasis (7), VASP plays an essential role in many diseases, such as cancer metastasis (8,9), thrombosis (10), arteriosclerosis (11) and nephritis (12).…”

Section: Introductionmentioning

confidence: 99%

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Vasodilator-stimulated phosphoprotein regulates osteosarcoma cell migration

Wei

et al. 2011

Oncol Rep

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Abstract. Vasodilator-stimulated phosphoprotein (VASP) has been reported to play an important role in the process of cell migration and tumor metastasis. However, to date, no study has examined VASP expression and its function in osteocarcoma cells. In this study, we analyzed the effect of VASP on osteosarcoma cell migration and the signal transduction pathways involved. We used two osteosarcoma cell strains (Mg-63 and Saos-2 cells) with different metastatic potential. Silencing of VASP gene expression was carried out using RNA interference in these cells. Knockdown of expression at the transcriptional or translational level was determined by RT-PCR or Western blot analysis, respectively. The metastatic potential of the tumor cells was determined by a wound healing migration assay. VASP mRNA expression was also determined in 30 human osteosarcoma samples. Furthermore, Rac1 was determined as a regulator of VASP function. RT-PCR and Western blotting showed that Mg-63 cells had a significantly higher VASP expression at both the transcriptional and translational levels compared to Saos-2 cells. The wound healing assay revealed that Mg-63 cells had more migratory potential compared to Saos-2 cells. The effect was found to be reversible when VASP was knocked down by siRNA in Mg-63 cells. Specimens from human patients with metastases had higher VASP expression compared to specimens of patients without metastases. Knockdown of Rac1 resulted in inhibition of VASP expression in sarcoma cells. These results suggest that VASP protein regulates osteosarcoma cell migration and metastasis. Rac1 and VASP interaction may be a potential target for osteosarcoma treatment. IntroductionOsteosarcoma is the most prevalent primary malignant bone tumor in children and young adults. Although the life expectancy of osteosarcoma patients has been prolonged due to improvement of neoadjuvant chemotherapy and surgical resection during the past three decades, the long-term survival and quality of life is still unsatisfactory. Poor outcome of osteosarcoma is mainly caused by metastatic disease, and previous studies have demonstrated that more than 30% of patients already display distant metastasis without clinical detectable signs at the time of diagnosis (1,2).Vasodilator-stimulated phosphoprotein (VASP), a member of the Ena/VASP family, has been implicated in regulating key cellular functions, such as shape change, adhesion and migration, which is mainly due to its ability to modify dynamic action cytoskeleton (3). In addition to its role in normal cell growth (4,5), embryonic development (6) and homeostasis (7), VASP plays an essential role in many diseases, such as cancer metastasis (8,9), thrombosis (10), arteriosclerosis (11) and nephritis (12).Expression of VASP has been reported to be dysregulated in several types of malignancies and is relevant to tumor metastasis. For example, its level was found to be significantly increased in lung adenocarcinomas and gastric carcinomas compared to normal tissue, and this increase was correlated wit...

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Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Vasodilator-stimulated phosphoprotein regulates osteosarcoma cell migration

Wei

et al. 2011

Oncol Rep

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Chlorotoxin targets ERα/VASP signaling pathway to combat breast cancer

Wang

Han

et al. 2019

Cancer Medicine

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Breast cancer is one of the most common malignant tumors among women worldwide. About 70‐75% of primary breast cancers belong to estrogen receptor (ER)‐positive breast cancer. In the development of ER‐positive breast cancer, abnormal activation of the ERα pathway plays an important role and is also a key point leading to the failure of clinical endocrine therapy. In this study, we found that the small molecule peptide chlorotoxin (CTX) can significantly inhibit the proliferation, migration and invasion of breast cancer cells. In in vitro study, CTX inhibits the expression of ERα in breast cancer cells. Further studies showed that CTX can directly bind to ERα and change the protein secondary structure of its LBD domain, thereby inhibiting the ERα signaling pathway. In addition, we also found that vasodilator stimulated phosphoprotein (VASP) is a target gene of ERα signaling pathway, and CTX can inhibit breast cancer cell proliferation, migration, and invasion through ERα/VASP signaling pathway. In in vivo study, CTX significantly inhibits growth of ER overexpressing breast tumor and, more importantly, based on the mechanism of CTX interacting with ERα, we found that CTX can target ER overexpressing breast tumors in vivo. Our study reveals a new mechanism of CTX anti‐ER‐positive breast cancer, which also provides an important reference for the study of CTX anti‐ER‐related tumors.

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Interaction of the Bioactive Flavonol, Icariin, with the Essential Human Solute Carrier Transporters

Cheung

Zheng

et al. 2013

J Biochem Mol Toxicol

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Solute carrier transporters (SLCs), in particular the organic anion transporting polypeptides (OATPs) and organic anion/cation transporters (OATs/OCTs), are responsible for the cellular entry of many clinically important drugs in body. They largely influence drug safety and efficacy. Icariin is a flavonol widely present in many herbal preparations, which is used to improve sexual function and prevent osteogenesis. However, precautions are necessary in therapies containing icariin due to its involvement in drug-drug/herb interactions, possibly mediated through competing drug uptake via membrane-transporter proteins. This study is the first to comprehensively evaluate the interactions between icariin and a range of essential SLCs. Our data demonstrated that icariin can significantly inhibit OATP1B3- and OATP2B1-mediated cellular uptake of specific substrates (IC₅₀ of 3.0 ± 1.3 and 6.4 ± 1.9 μM, respectively). Our study revealed that icariin can potentially compete with coadministrated drugs for particular SLCs, which may impact the therapeutic outcome of regimens.

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Icariin exterts negative effects on human gastric cancer cell invasion and migration by vasodilator-stimulated phosphoprotein via Rac1 pathway

Cited by 60 publications

References 34 publications

Vasodilator-stimulated phosphoprotein regulates osteosarcoma cell migration

Vasodilator-stimulated phosphoprotein regulates osteosarcoma cell migration

Chlorotoxin targets ERα/VASP signaling pathway to combat breast cancer

Interaction of the Bioactive Flavonol, Icariin, with the Essential Human Solute Carrier Transporters

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