Suramin inhibits cell proliferation in ovarian and cervical cancer by downregulating heparanase expression

Li, Huaping; Li, Huali; Qu, Hongjie; Zhao, Minghui; Yuan, Bo; Cao, Minghua; Cui, Jinquan

doi:10.1186/s12935-015-0196-y

Cited by 42 publications

(21 citation statements)

References 46 publications

(43 reference statements)

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“…Similarly, suramin also induced a G0/G1 cell cycle block of up to 39% and inhibited S phase up to 98% of the cell population. These findings are similar to those reported by HuaPing Li et al who found inhibition of cell proliferation by suramin in ovarian and cervical cancer by down regulating HPSE expression [ 47 ]. These results are in good correlation with our results showing that HPSE regulated EMT is inhibited by suramin, an HPSE inhibitor.…”

Section: Discussionsupporting

confidence: 92%

The close relationship between heparanase and epithelial mesenchymal transition in gastric signet-ring cell adenocarcinoma

et al. 2018

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Heparanase (HPSE), a heparan sulfate-specific endo-β-D-glucuronidase, plays an important role in tumor cell metastasis through the degradation of extracellular matrix heparan sulfate proteoglycans. Suramin, a polysulfonated naphthylurea, is an inhibitor of HPSE with suramin analogues. Our objective was to analyze the HPSE involvement in gastric signet ring cell adenocarcinoma (SRCA) invasion. High expression of HPSE mRNA and protein was found in the tumor and in ascites of SRCA as well as in KATO-III cell line. Beside of collagen-I, growth factors (TGF-β1 and VEGF-A, except FGF-2) and epithelial mesenchymal transition (EMT) markers (Snail, Slug, Vimentin, α-SMA and Fibronectin, except E-cadherin) were found higher in main nodules of SRCA as compared to peritumoral sites. Among MDR proteins, MDR-1 and LRP (lung resistance protein) were highly expressed in tumor cells. The formation of 3D cell spheroids was found to be correlated with their origin (adherent or non-adherent KATO-III). After treatment of KATO-III cells with a HPSE inhibitor (suramin), cell proliferation and EMT-related markers, besides collagen-1 expression, were down regulated. In conclusion, in SRCA, HPSE via an autocrine secretion is involved in acquisition of mesenchymal phenotype and tumor cell malignancy. Therefore, HPSE could be an interesting pharmacological target for the treatment of SRCA.

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Section: Discussionsupporting

confidence: 92%

The close relationship between heparanase and epithelial mesenchymal transition in gastric signet-ring cell adenocarcinoma

et al. 2018

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“…Suramin is a hexasulfonated naphthylurea compound that is a market-authorized drug used for antiparasitic treatment since 1921. However, suramin possesses miscellaneous phar-macological effects, including antitumor (8,9), anti-inflammation (10), and antivirus activities (11)(12)(13)(14) etc. Suramin was the first documented HIV-1 reverse transcriptase inhibitor tested in clinical experiments; however, the side effects of the systemic drug delivery of this drug over a long-term treatment resulted in the failure of these clinical trials (15).…”

Section: Seminal Amyloid Fibrils Are Made Up Of Naturally Occurring Pmentioning

confidence: 99%

The anti-parasitic drug suramin potently inhibits formation of seminal amyloid fibrils and their interaction with HIV-1

Tan

Cheng

et al. 2019

Journal of Biological Chemistry

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“…Recently, suramin has been demonstrated to be effective in reducing peritoneal fibrosis [ 10 ], chronic renal fibrosis [ 11 ], and the fibrosis of proliferative eye disease [ 12 ]. Also, it was found that suramin could inhibit cell proliferation [ 13 – 15 ], which implicated that suramin might be useful in prevention of epidural fibrosis through inhibiting the proliferation of fibroblasts.…”

Section: Introductionmentioning

confidence: 99%

The effect of suramin on inhibiting fibroblast proliferation and preventing epidural fibrosis after laminectomy in rats

Dai

Yan

et al. 2016

J Orthop Surg Res

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BackgroundEpidural fibrosis often causes serious complications in patients after lumbar laminectomy and discectomy and is associated with the proliferation of fibroblasts. Suramin is known to have an obvious inhibitory effect on the coactions of many growth factors and their receptors, but little was previously known about the effect of suramin on fibroblast proliferation and the progress of epidural fibrosis.MethodsWe illustrated the effect of suramin on cultured fibroblasts of rats with different concentrations (0, 200, 400, 600 mg/l). The proliferation of suramin-treated fibroblasts was evaluated by CCK-8 and western blot analysis. Additionally, in a rat model of laminectomy, different concentrations of suramin (100, 200, and 300 mg/ml) and saline were applied to the laminectomy sites locally. The effect of suramin on preventing epidural fibrosis was detected by the Rydell classification, hydroxyproline content, histological analysis, and collagen density analyses.ResultsThe results of CCK-8 shown that suramin could significantly inhibit fibroblasts proliferation in a dose-dependent manner. The western blotting shown that the expression levels of the cell proliferation markers such as cyclin D1, cyclin E, and PCNA were down-regulated. Moreover, in a rat model, we found that suramin could reduce epidural fibrosis as well as inhibit fibroblast proliferation, and 300 mg/ml suramin had better effect.ConclusionsTopical application of suramin could reduce epidural fibrosis after laminectomy, and the application of suramin could inhibit the proliferation of fibroblasts in rats. This study indicates that suramin is a potent antifibrotic agent that may have therapeutic potential for patients with epidural fibrosis.

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Suramin inhibits cell proliferation in ovarian and cervical cancer by downregulating heparanase expression

Cited by 42 publications

References 46 publications

The close relationship between heparanase and epithelial mesenchymal transition in gastric signet-ring cell adenocarcinoma

The close relationship between heparanase and epithelial mesenchymal transition in gastric signet-ring cell adenocarcinoma

The anti-parasitic drug suramin potently inhibits formation of seminal amyloid fibrils and their interaction with HIV-1

The effect of suramin on inhibiting fibroblast proliferation and preventing epidural fibrosis after laminectomy in rats

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