Cucurbitacins: A Systematic Review of the Phytochemistry and Anticancer Activity

2015 ◽  
Vol 43 (07) ◽  
pp. 1331-1350 ◽  
Author(s):  
Yuee Cai ◽  
Xiefan Fang ◽  
Chengwei He ◽  
Peng Li ◽  
Fei Xiao ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Mapk Signaling ◽  
Research Progress ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Cycle Arrest ◽  
Anticancer Effects ◽  
And Migration

Cucurbitacins are highly oxidized tetracyclic triterpenoids that are widely present in traditional Chinese medicines (Cucurbitaceae family), possess strong anticancer activity, and are divided into 12 classes from A to T with over 200 derivatives. The eight most active cucurbitacin components against cancer are cucurbitacin B, D, E, I, IIa, L glucoside, Q, and R. Their mechanisms of action include antiproliferation, inhibition of migration and invasion, proapoptosis, and cell cycle arrest promotion. Cucurbitacins are also found to be the inhibitors of JAK-STAT3, Wnt, PI3K/Akt, and MAPK signaling pathways, which play important roles in the apoptosis and survival of cancer cells. Recently, new studies have discovered synergistic anticancer effects by using cucurbitacins together with clinically approved chemotherapeutic drugs, such as docetaxel and methotrexate. This paper provides a summary of recent research progress on the anticancer property of cucurbitacins and the various intracellular signaling pathways involved in the regulation of cancer cell proliferation, death, invasion, and migration. Therefore, cucurbitacins are a class of promising anticancer drugs to be used alone or be intergraded in current chemotherapies and radiotherapies to treat many types of cancers.

scholarly journals Echinacoside Suppresses the Progression of Breast Cancer by Downregulating the Expression of miR-4306 and miR-4508

2021 ◽  
Vol 20 ◽  
pp. 153473542110626
Author(s):  
Peng Bian ◽  
Chuan Liu ◽  
Wei Hu ◽  
Yu Ding ◽  
Shusheng Qiu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Antitumor Effect ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Anticancer Effects ◽  
And Migration ◽  
Cancer Tissues

The main treatment of breast cancer includes surgical resection, radiotherapy, chemotherapy, endocrine therapy, and molecular targeted therapy, but the outcomes remain unsatisfactory. Previous studies demonstrated that echinacoside, microRNA (miRNA/miR)-4306 and miR-4508 were associated with lymph node metastasis, chemoresistance and self-renewal capability in breast cancer, but in-depth studies on the underlying mechanism of their anticancer effects have not been performed to date. In order to identify the role of miR-4306 and miR-4508, and the mechanism of the antitumor effect of echinacoside in breast cancer, the present study first examined the expression of miR-4306 and miR-4508 in breast cancer tissues to examine their possible role in the development of breast cancer, then evaluated the effect of echinacoside on the expression of miR-4306 and miR-4508 on the viability, apoptosis, cell cycle, migration, and invasion abilities of breast cancer cells to explore the anti-cancer effect of echinacoside and the involvement of miR-4306 and miR-4508. Finally, the breast cancer cells and mice bearing breast cancer xenografts were treated with echinacoside and inhibitors of miR-4508 or miR-4306 to confirm their role on the anticancer effect of echinacoside. The results showed that miR-4306 and miR-4508 were decreased in breast cancer tissues and cells. Echinacoside inhibited cell proliferation, invasion and migration, and promoted the apoptosis of breast cancer cells by downregulating the expression of miR-4306 and miR-4508. In conclusion, this is the first study to show the association between echinacoside and miRNAs in cancer. The present study elucidates an underlying molecular mechanism of the antitumor effect of echinacoside on breast cancer, and thus may contribute to preventive and therapeutic strategies for breast cancer.

Anlotinib Inhibits Cell Proliferation, Migration and Invasion via Suppression of c-met Pathway and Activation of ERK1/2 Pathway in H446 Cells

2020 ◽  
Vol 20 ◽  
Author(s):  
Xiali Tang ◽  
Ying Zheng ◽  
Demin Jiao ◽  
Jun Chen ◽  
Xibang Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Viability ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Cell Cycle Distribution ◽  
M Cell ◽  
Invasion And Migration ◽  
Cycle Arrest ◽  
And Migration

Background: Small Cell Lung Cancer (SCLC) represents the most aggressive pulmonary neoplasm and is often diagnosed at late stage with limited survival, despite combined chemotherapies. The purpose of this study was to investigate the effect of anlotinib on SCLC and the potential molecular mechanisms. Methods: Cell viability was assessed by CCK-8 assay to determine the adequate concentration of anlotinib. Then, effects of anlotinib on cell apoptosis, cell cycle distribution, migration and invasion were analyzed by flow cytometry, PI staining, wound healing assay and transwell assay, respectively. The protein expression of c-met and ERK1/2 pathways in H446 cells were assessed by western blot analysis. Result: In this study, we found that anlotinib significantly reduced the cell viability of H446 cells, induced G2/M cell cycle arrest and decreased invasion and migration of H446 cells. Futhermore, we also found that anlotinib could suppress c-met signal transduction and activate the ERK1/2 pathway in H446 cells. More importantly, c-met was involved in the effects of anlotinib on migration and invasion in H446 cells. Conclusion: Taken together, our results demonstrated that anlotinib was a potential anticancer agent that inhibited cell proliferation, migration and invasion via suppression of the c-met pathway and activation of the ERK1/2 pathway in H446 cells.

Glioblastoma invasion and NMDA receptors: A novel prospect

2019 ◽  
Vol 106 (3) ◽  
pp. 250-260 ◽  
Author(s):  
DN Nandakumar ◽  
P Ramaswamy ◽  
C Prasad ◽  
D Srinivas ◽  
K Goswami
Keyword(s):  
Glutamate Receptors ◽  
Cell Lines ◽  
Intracellular Signaling ◽  
Transcript Level ◽  
Glioblastoma Cells ◽  
Invasion And Migration ◽  
Matrigel Invasion ◽  
Nmdar Activation ◽  
And Migration

Purpose Glioblastoma cells create glutamate-rich tumor microenvironment, which initiates activation of ion channels and modulates downstream intracellular signaling. N-methyl-D-aspartate receptors (NMDARs; a type of glutamate receptors) have a high affinity for glutamate. The role of NMDAR activation on invasion of glioblastoma cells and the crosstalk with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is yet to be explored. Main methods LN18, U251MG, and patient-derived glioblastoma cells were stimulated with NMDA to activate NMDAR glutamate receptors. The role of NMDAR activation on invasion and migration and its crosstalk with AMPAR were evaluated. Invasion and migration of glioblastoma cells were investigated by in vitro trans-well Matrigel invasion and trans-well migration assays, respectively. Expression of NMDARs and AMPARs at transcript level was evaluated by quantitative real-time polymerase chain reaction. Results We determined that NMDA stimulation leads to enhanced invasion in LN18, U251MG, and patient-derived glioblastoma cells, whereas inhibition of NMDAR using MK-801, a non-competitive antagonist of the NMDAR, significantly decreased the invasive capacity. Concordant with these findings, migration was significantly augmented by NMDAR in both cell lines. Furthermore, NMDA stimulation upregulated the expression of GluN2 and GluA1 subunits at the transcript level. Conclusions This study demonstrated the previously unexplored role of NMDAR in invasion of glioblastoma cells. Furthermore, the expression of the GluN2 subunit of NMDAR and the differential overexpression of the GluA1 subunit of AMPAR in both cell lines provide a plausible rationale of crosstalk between these calcium-permeable subunits in the glutamate-rich microenvironment of glioblastoma.

Wnt/beta-catenin and PI3K/Akt/mTOR Signaling Pathways in Glioblastoma: Two Main Targets for Drug Design: A Review

2020 ◽  
Vol 26 (15) ◽  
pp. 1729-1741 ◽  
Author(s):  
Seyed H. Shahcheraghi ◽  
Venant Tchokonte-Nana ◽  
Marzieh Lotfi ◽  
Malihe Lotfi ◽  
Ahmad Ghorbani ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Chemotherapy Resistance ◽  
Wnt Signaling Pathway ◽  
Therapeutic Interventions ◽  
Beta Catenin ◽  
Clinical Prognosis ◽  
Invasion And Migration ◽  
And Migration

: Glioblastoma (GBM) is the most common and malignant astrocytic glioma, accounting for about 90% of all brain tumors with poor prognosis. Despite recent advances in understanding molecular mechanisms of oncogenesis and the improved neuroimaging technologies, surgery, and adjuvant treatments, the clinical prognosis of patients with GBM remains persistently unfavorable. The signaling pathways and the regulation of growth factors of glioblastoma cells are very abnormal. The various signaling pathways have been suggested to be involved in cellular proliferation, invasion, and glioma metastasis. The Wnt signaling pathway with its pleiotropic functions in neurogenesis and stem cell proliferation is implicated in various human cancers, including glioma. In addition, the PI3K/Akt/mTOR pathway is closely related to growth, metabolism, survival, angiogenesis, autophagy, and chemotherapy resistance of GBM. Understanding the mechanisms of GBM’s invasion, represented by invasion and migration, is an important tool in designing effective therapeutic interventions. This review will investigate two main signaling pathways in GBM: PI3K/Akt/mTOR and Wnt/beta-catenin signaling pathways.

miR-375 inhibits the proliferation, migration and invasion of esophageal squamous cell carcinoma by targeting XPR1

2020 ◽  
Vol 20 ◽  
Author(s):  
Wenbin Wu ◽  
Yangmei Zhang ◽  
Xiaowu Li ◽  
Xiang Wang ◽  
Yuan Yuan
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Promoting Effect ◽  
Dual Luciferase Assay ◽  
Invasion And Migration ◽  
And Migration

Objective: The purpose of this study was to explore the mechanism of the miR-375/XPR1 axis in esophageal squamous cell carcinoma (ESCC) and provide a new idea for targeted therapy of ESCC. Methods: Differentially expressed genes in GEO and TCGA databases were analyzed by bioinformatics. The expression levels of miR-375 and XPR1 mRNA were detected by qRT-PCR. Protein expression of XPR1 was detected by western blot. Bioinformatics analysis and dual luciferase assay were conducted to confirm the targeting relationship between miR-375 and XPR1. The viability, proliferation, migration and invasion of cells in each treatment group were detected by CCK-8, colony formation, wound healing and Transwell assays. Results: Significantly down-regulated miR-375 and remarkably up-regulated XPR1 were observed in ESCC tissue and cells. Overexpression of miR-375 inhibited proliferation, invasion and migration of ESCC cells, and greatly reduced the promoting effect of XPR1 overexpression on cell proliferation, migration and invasion. Dual luciferase assay confirmed that miR-375 targeted and inhibited XPR1 expression in ESCC. Conclusion: These results demonstrate the regulatory role of the miR-375/XPR1 axis in ESCC cells and provide a new potential target for the precise treatment of patients with ESCC.

Hispidulin inhibits proliferation, migration, and invasion by promoting autophagy via regulation of PPARγ activation in prostate cancer cells and xenograft models

2020 ◽  
Author(s):  
Yuanyuan Wang ◽  
Shanqi Guo ◽  
Yingjie Jia ◽  
Xiaoyu Yu ◽  
Ruiyu Mou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Flavonoid Compound ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Invasion And Migration ◽  
Beneficial Effects ◽  
Anticancer Properties ◽  
Xenograft Models ◽  
And Migration

ABSTRACT Prostate cancer (PCa) is one of the important factors of cancer deaths especially in the western countries. Hispidulin (4′,5,7-trihydroxy-6-methoxyflavone) is a phenolic flavonoid compound proved to possess anticancer properties, but its effects on PCa are left to be released. The aims of this study were to investigate the effects and the relative mechanisms of Hispidulin on PCa development. Hispidulin administration inhibited proliferation, invasion, and migration, while accelerated apoptosis in Du145 and VCaP cells, which was accompanied by PPARγ activation and autophagy enhancement. The beneficial effects of Hispidulin could be diminished by PPARγ inhibition. Besides, Hispidulin administration suppressed PCa tumorigenicity in Xenograft models, indicating the anticancer properties in vivo. Therefore, our work revealed that the anticancer properties of Hispidulin might be conferred by its activation on PPARγ and autophagy.

scholarly journals miR-373-3p Regulates Invasion and Migration Abilities of Trophoblast Cells via Targeted CD44 and Radixin

2021 ◽  
Vol 22 (12) ◽  
pp. 6260
Author(s):  
Hyun-Jung Lee ◽  
Seung Mook Lim ◽  
Hee Yeon Jang ◽  
Young Ran Kim ◽  
Joon-Seok Hong ◽  
...  
Keyword(s):  
Preterm Labor ◽  
Target Genes ◽  
Gene Array ◽  
Migration And Invasion ◽  
Trophoblast Cells ◽  
Invasion And Migration ◽  
Mirna Array ◽  
Qrt Pcr ◽  
Putative Target ◽  
And Migration

Preterm labor (PTL) is one of the obstetric complications, and is known to be associated with abnormal maternal inflammatory response and intrauterine inflammation and/or infection. However, the expression of specific miRNAs associated with PTL is not clear. In this study, we performed combination analysis of miRNA array and gene array, and then selected one miRNA (miR-373-3p) and its putative target genes (CD44 and RDX) that exhibited large expression differences in term and PTL placentas with or without inflammation. Using qRT-PCR and luciferase assays, we confirmed that miR-373-3p directly targeted CD44 and RDX. Overexpression of miR-373-3p reduced the migration and invasion of trophoblast cells, while inhibition of miR-373-3p restored the migration and invasion abilities of trophoblast cells. Finally, we validated the expression of miR-373-3p and its target genes in clinical patients’ blood. miR-373-3p was increased in PTL patients’ blood, and was the most expressed in PTL patients’ blood with inflammation. In addition, by targeting the miR-373-3p, CD44 and RDX was decreased in PTL patients’ blood, and their expression were the lowest in PTL patients’ blood with inflammation. Taken together, these findings suggest that miR-373-3p and its target genes can be potential biomarkers for diagnosis of PTL.

scholarly journals Long non-coding RNA XIST regulates ovarian cancer progression via modulating miR-335/BCL2L2 axis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qingjuan Meng ◽  
Ningning Wang ◽  
Guanglan Duan
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Invasion And Migration ◽  
Non Coding Rna ◽  
And Migration ◽  
Long Non Coding Rna

Abstract Background X inactivation-specific transcript (XIST) is the long non-coding RNA (lncRNA) related to cancer, which is involved in the development and progression of various types of tumor. However, up to now, the exact role and molecular mechanism of XIST in the progression of ovarian cancer are not clear. We studied the function of XIST in ovarian cancer cells and clinical tumor specimens. Methods RT-qPCR was performed to detect the expression levels of miR-335 and BCL2L2 in ovarian cancer cells and tissues. MTT and transwell assays were carried out to detect cell proliferation, migration, and invasion abilities. Western blot was performed to analyze the expression level of BCL2L2. The interaction between miR-335 and XIST/BCL2L2 was confirmed using a luciferase reporter assay. Results The inhibition of XIST can inhibit the proliferation invasion and migration of human ovarian cancer cells. In addition, the miR-335/BCL2L2 axis was involved in the functions of XIST in ovarian cancer cells. These results suggested that XIST could regulate tumor proliferation and invasion and migration via modulating miR-335/BCL2L2. Conclusion XIST might be a carcinogenic lncRNA in ovarian cancer by regulating miR-335, and it can serve as a therapeutic target in human ovarian cancer.

Proteasome inhibitor MG132 induces apoptosis in human osteosarcoma U2OS cells

2021 ◽  
pp. 096032712110179
Author(s):  
Han Ki Lee ◽  
See-Hyoung Park ◽  
Myeong Jin Nam
Keyword(s):  
Signaling Pathways ◽  
Proteasome Inhibitor ◽  
Migration And Invasion ◽  
Apoptotic Signaling ◽  
Antiapoptotic Proteins ◽  
Human Osteosarcoma ◽  
Anticancer Effects ◽  
Caspase 7 ◽  
U2os Cells ◽  
Western Blotting Assay

MG132 is a potent, reversible, and cell-permeable 20S proteasome inhibitor and it is derived from a Chinese medicinal plant. The purpose of this study is to investigate the anticancer effects of MG132 against human osteosarcoma U2OS cells. We first performed MTT and colony formation assays to investigate the anti-proliferative effects of MG132. The results demonstrated that MG132 suppressed the proliferation of U2OS cells. Furthermore, we found that treatment with MG132 increased apoptosis and induced DNA damage in U2OS cells. Additionally, zymography, wound healing, and invasion assays showed that MG132 suppressed the enzymatic activity of matrix metalloproteinases, cell migration, and invasion, respectively of U2OS cells. Furthermore, western blotting assay was performed to investigate the apoptotic signaling pathways in MG132-treated U2OS cells. Our results showed that MG132 downregulated the expression of antiapoptotic proteins, including CDK2, CDK4, Bcl-xL, and Bcl-2, whereas it upregulated the expression of proapoptotic proteins, including p21, p27, p53, p-p53 (ser15, ser20, and ser46), cleaved forms of caspase-3, caspase-7, caspase-9, and PARP, and FOXO3 in U2OS cells. These results demonstrated that MG132 activated apoptotic signaling pathways in U2OS cells. Interestingly, MG132 downregulated the phosphorylation of Akt and Erk. Taken together, our results suggest that MG132 has anticancer effects in U2OS cells. Therefore, MG132 may be a potential therapeutic agent for the treatment of osteosarcoma.

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