Novel 1, 3-N, O-Spiroheterocyclic compounds inhibit heparanase activity and enhance nedaplatin-induced cytotoxicity in cervical cancer cells

Song, Yanan; Hu, Bin; Qu, Hongjie; Wang, Lu; Zhang, Yunxiao; Tao, Jinchao; Cui, Jinquan

doi:10.18632/oncotarget.8959

Cited by 10 publications

(9 citation statements)

References 24 publications

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“…This result is consistent with one previous study, which used NDP on human gastric cancer AZ-521 cells [21]. Other studies also found that different cisplatin drugs have similar effects on cell cycle in different cancer types [22][23][24], suggesting that cell cycle blockage in S phase may be one of the mechanisms in which NDP-induced apoptosis [25]. In our study, we found that apoptotic rate increased significantly in NDP or MVIH siRNA treated MDR cells, indicating that NDP could improve chemotherapeutic sensitivity of A549 and H1650 cells and promote apoptosis by down-regulating MVIH.…”

Section: Discussionsupporting

confidence: 93%

Nedaplatin reduces multidrug resistance of non-small cell lung cancer by downregulating the expression of long non-coding RNA MVIH

et al. 2020

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Cisplatin-based chemotherapy is the standard treatment for non-small cell lung cancer (NSCLC). However, drug resistance emergences after treatment. Long non-coding RNA microvascular invasion in hepatic cancer (MVIH) plays an important role in drug resistance in a variety of cancers. This study investigates the role of nedaplatin on multidrug resistance in NSCLC and its relationship with MVIH. Lung cancer A549 and H1650 cells were treated with cisplatin to obtain multidrug-resistant A549/DDP and H1650/ DDP cells. A549/DDP and H1650/ DDP cells were treated with nedaplatin, MVIH siRNA and siRNA NC. It was found that both MVIH siRNA and nedaplatin significantly reduce the mRNA expression of MVIH in A549/DDP and H1650/ DDP cells. MTT assay showed that the proliferation of MDR cells was significantly higher than that of other cells. Nedaplatin and MVIH siRNA significantly inhibit the proliferation of A549 and H1650 cells. The results of colony formation assay were consistence with MTT results. Nedaplatin and MVIH siRNA significantly reduced colony formation in MDR cells. Flow cytometry showed that NDP and MVIH siRNA significantly decrease the proportion of cells in G0/G1 and increase the proportion of cells in S phase compared with untreated and MDR cells. The apoptotic rate of MDR cells was significantly lower than that of other cells, while the apoptosis rate of cells in NDP and MVIH siRNA group was significantly higher than that of the other three groups of cells. Wound healing assay and Transwell chamber experiments confirmed that both NDP and MVIH siRNA significantly reduced the migration and invasion abilities of MDR cells. The expression of E-cadherin in MDR cells was significantly lower than that in untreated cells, and the expression of N-cad, α-SMA and Vimentin significantly increased in the MDR cells. NPD and MVIH siRNA reverse the EMT process. In conclusion, LncRNA MVIH is upregulated in drug resistant NSCLC cells. Nedaplatin can reduce the expression of MVIH and reverse EMT process, thus reversing the drug resistance of cisplatin in non-small cell lung cancer cells.

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Section: Discussionsupporting

confidence: 93%

Nedaplatin reduces multidrug resistance of non-small cell lung cancer by downregulating the expression of long non-coding RNA MVIH

et al. 2020

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“…Despite the improvement of therapeutic methods and diagnostic tools, the overall prognosis of patients has not been improved . Many patients do not respond well to any currently available treatments . Therefore, exploration of pathogenesis and identification of novel biomarkers is imperative.…”

Section: Introductionmentioning

confidence: 99%

“…2,9 Many patients do not respond well to any currently available treatments. 10 Therefore, exploration of pathogenesis and identification of novel biomarkers is imperative.…”

mentioning

confidence: 99%

CD38 enhances the proliferation and inhibits the apoptosis of cervical cancer cells by affecting the mitochondria functions

Liao

Xiao

Chen

et al. 2017

Molecular Carcinogenesis

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Cervical cancer is one of the most common malignant tumors in women all over the world. The exact mechanism of occurrence and development of cervical cancer has not been fully elucidated. CD38 is a type II transmembrane glycoprotein, which was found to mediate diverse activities, including signal transduction, cell adhesion, and cyclic ADP-ribose synthesis. Here, we reported that CD38 promoted cell proliferation and inhibited cell apoptosis in cervical cancer cells by affecting the mitochondria functions. We established stable cervical cancer cell lines with CD38 over-expressed. CCK8 assay and colony formation assay indicated that CD38 promoted cervical cancer cell proliferation. Nude mouse tumorigenicity assay showed that CD38 significantly promotes tumor growth in vivo. CD38 also induced S phase accumulation in cell cycle analysis and suppressed cell apoptosis in cervical cancer cells. Meanwhile, flow cytometry analysis of mitochondria functions suggested that CD38 decreased intracellular Ca levels in cervical cancer cells and CD38 was involved in down-regulation of ROS levels and prevented mitochondrial apoptosis in cervical cancer cells. The percentage of cells with loss of mitochondrial membrane potential (Δψm) in CD38-overexpressed cervical cancer cells was less than control groups. Furthermore, we found an up-regulation of MDM2, cyclinA1, CDK4, cyclinD1, NF-kB P65, c-rel, and a downregulation of P53, P21, and P38 by Western blot analysis. These results indicated that CD38 enhanced the proliferation and inhibited the apoptosis of cervical cancer cells by affecting the mitochondria functions.

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“…Importantly, 55 strongly reduced the mRNA and protein levels of heparanase. This study suggested that targeted inhibition of heparanase may prove to be an effective therapy against cervical cancer (Song et al., 2016).…”

Section: Synthetic Heparanase Inhibitorsmentioning

confidence: 94%

Targeting Heparanase in Cancer: Inhibition by Synthetic, Chemically Modified, and Natural Compounds

et al. 2019

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Heparanase is an endoglycosidase involved in remodeling the extracellular matrix and thereby in regulating multiple cellular processes and biological activities. It cleaves heparan sulfate (HS) side chains of HS proteoglycans into smaller fragments and hence regulates tissue morphogenesis, differentiation, and homeostasis. Heparanase is overexpressed in various carcinomas, sarcomas, and hematological malignancies, and its upregulation correlates with increased tumor size, tumor angiogenesis, enhanced metastasis, and poor prognosis. In contrast, knockdown or inhibition of heparanase markedly attenuates tumor progression, further underscoring the potential of anti-heparanase therapy. Heparanase inhibitors were employed to interfere with tumor progression in preclinical studies, and selected heparin mimetics are being examined in clinical trials. However, despite tremendous efforts, the discovery of heparanase inhibitors with high clinical benefit and minimal adverse effects remains a therapeutic challenge. This review discusses the key roles of heparanase in cancer progression focusing on the status of natural, chemically modified, and synthetic heparanase inhibitors in various types of malignancies.

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Novel 1, 3-N, O-Spiroheterocyclic compounds inhibit heparanase activity and enhance nedaplatin-induced cytotoxicity in cervical cancer cells

Cited by 10 publications

References 24 publications

Nedaplatin reduces multidrug resistance of non-small cell lung cancer by downregulating the expression of long non-coding RNA MVIH

Nedaplatin reduces multidrug resistance of non-small cell lung cancer by downregulating the expression of long non-coding RNA MVIH

CD38 enhances the proliferation and inhibits the apoptosis of cervical cancer cells by affecting the mitochondria functions

Targeting Heparanase in Cancer: Inhibition by Synthetic, Chemically Modified, and Natural Compounds

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