Cordycepin suppresses cell proliferation and migration by targeting CLEC2 in human gastric cancer cells via Akt signaling pathway

Wáng, Ying; Lv, You; Liu, Te Si; Yan, Wen; Chen, Li Yan; Li, Zhu Hu; Piao, Ying; An, Ren Bo; Lin, Zhen; Ren, Xiang

doi:10.1016/j.lfs.2019.03.025

Cited by 32 publications

(25 citation statements)

References 16 publications

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“…Therefore, we analyzed whether this signaling pathway was involved in the induction of T24 cell apoptosis by cordycepin, and found cordycepin suppressed the phosphorylated levels of Akt, as well as PI3K. This means that the PI3K/Akt signaling pathway is inactivated by cordycepin treatment, and the results are in good agreement with previous studies performed on several other cancer cell lines (31)(32)(33)(34)(35)(36)42,51). Furthermore, in line with our previous study using leukemia cells (36), LY294002, a pharmacological inhibitor of PI3K, significantly enhanced the apoptotic effect of cordycepin and further reduced cell viability, supposing that cordycepin-induced apoptosis is mediated by blocking the PI3K/Akt signaling pathway.…”

Section: Discussionsupporting

confidence: 89%

“…It has also been found that the increase of ROS production in leukemia, gastric and prostate cancer cells plays an important role in the induction of intrinsic apoptosis pathway (28)(29)(30). In addition, the anticancer effects of cordycepin involve the disturbance of various cell signaling pathways, and in particular, cordycepininduced apoptosis in human gastric and ovarian cancer cells and leukemia and glioma cells was accompanied by inactivation of the PI3K/Akt signaling pathway (31)(32)(33)(34)(35)(36). Although the induction of apoptosis by cordycepin in a certain gastric cancer cell line was accompanied by the production of ROS and inactivation of the PI3K/Akt signaling pathway (24), the underlying mechanism of ROS involved in the inactivation of PI3K/Akt signaling pathway by cordycepin is still not well known.…”

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confidence: 99%

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Cordycepin induces apoptosis in human bladder cancer T24 cells through ROS-dependent inhibition of the PI3K/Akt signaling pathway

Kim

Jae

Park

et al. 2019

BST

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Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

Cordycepin induces apoptosis in human bladder cancer T24 cells through ROS-dependent inhibition of the PI3K/Akt signaling pathway

Kim

Jae

Park

et al. 2019

BST

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“…Most members of the family have the c-type carbohydrate recognition domain located on the outer surface of the cell, which under physical stress, can specifically identify and bind to proteins, lipids and carbohydrates in a ca 2+ -dependent manner (6). Dysfunctional C-type lectins have been reported in various pathological states, including cancer; for example, Wang et al (7) observed that c-type-lectin-like-2 promoted the proliferation and migration of gastric cancer cells by regulating the aKT signaling pathway. ni et al (8) demonstrated that high expression levels of the c-type lectin domain family 3 member a (clec3a) were positively associated with poor prognosis in patients with invasive ductal carcinoma of the breast.…”

Section: Suppression Of Clec3a Inhibits Osteosarcoma Cell Proliferatimentioning

confidence: 99%

Suppression of CLEC3A inhibits osteosarcoma cell proliferation and promotes their chemosensitivity through the AKT1/mTOR/HIF1α signaling pathway

Ren¹,

Pan²,

Hou³

et al. 2020

Mol Med Report

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osteosarcoma (oS) is a primary malignant tumor that occurs in bone, and mainly affects children and adolescents. c-type lectin domain family 3 member a (clec3a) is a member of the c-type lectin superfamily, which regulates various biological functions of cells. The present study aimed to identify the effects and related mechanisms of clec3a in the proliferation and chemosensitivity of oS cells. The expression of clec3a in oS was analyzed using the Gene Expression Omnibus data profile GSE99671, and its expression in OS samples was verified using reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemical staining. The relationship between the expression of clec3a and clinical traits in patients with oS was also analyzed, including age, tumor size, TnM stage and lymph node metastasis. cell counting Kit-8 assays, colony formation assays and cell cycle distribution analysis were used to determine the roles of clec3a in the proliferation and chemosensitivity of OS cells. Finally, RT-qPCR and western blotting were used to demonstrate the relationship between clec3a and the aKT1/mTor/hypoxia-inducible factor 1-α (HiF1α) pathway. Both the mrna and protein expression levels of clec3a were increased in oS tissues compared with adjacent non-tumor tissues, and this was positively associated with TnM stage and lymph node metastasis. The genetic knockdown of clec3a with small interfering rna decreased oS cell proliferation and colony formation, and induced G1 phase arrest, whereas the overexpression of clec3a increased oS cell proliferation and colony formation, and alleviated G1 phase arrest. The suppression of clec3a also promoted enhanced the chemosensitivity of oS cells to doxorubicin (doX) and cisplatin (cddP); it also inhibited the expression of aKT1, mTor and HiF1α, further to the nuclear localization of HiF1α, and HiF1α target gene expression levels, including VeGF, GluT1 and Mcl1 were also decreased. Furthermore, treatment with the aKT activator Sc79 blocked the inhibitory effects of clec3a silencing in oS cells. in conclusion, these findings suggested that CLEC3A may function as an oncogene in oS, and that the suppression of clec3a may inhibit oS cell proliferation and promote chemosensitivity through the aKT1/mTor/HiF1α signaling pathway.

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“…Previous studies have shown that cordycepin inhibits the cell cycle and induces apoptosis in non-small cell lung cancer by activating AMP-activated protein kinase signaling, without affecting the proliferation of normal lung epithelial cells (33). Additionally, cordycepin significantly inhibited the proliferation and migration of gastric cancer cells in a dose-dependent manner, and induced apoptosis (34). Furthermore, cordycepin inhibited the migration and invasion abilities of human gastric cancer cells by activating the PI3K/Akt signaling pathway, and ultimately upregulated the expression of the antimetastatic factor C-type lectin-like receptor 2 (34).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, cordycepin significantly inhibited the proliferation and migration of gastric cancer cells in a dose-dependent manner, and induced apoptosis (34). Furthermore, cordycepin inhibited the migration and invasion abilities of human gastric cancer cells by activating the PI3K/Akt signaling pathway, and ultimately upregulated the expression of the antimetastatic factor C-type lectin-like receptor 2 (34). However, it is unclear whether cordycepin affects the expression of CXCR4 in liver cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Cordycepin suppresses the migration and invasion of human liver cancer cells by downregulating the expression of CXCR4

et al. 2019

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Liver cancer is a worldwide threat to human health. High expression levels of C-X-C chemokine receptor type 4 (CXCR4) have been reported to promote the migration and invasion capacities of liver cancer cells. Cordycepin, extracted from Cordyceps militaris, has anti-inflammatory, antioxidant and anticancerous properties. Therefore, in the present study, migration assays, western blotting, reverse transcription-quantitative PCR and immunofluorescence analyses were conducted to determine whether cordycepin was able to suppress the migration and invasion abilities of liver cancer cells by inhibiting CXCR4 expression. The results suggested that cordycepin notably inhibited migration and invasion, and decreased the expression of CXCR4 in a dose-dependent manner. Activation of phosphorylated (p-) NF-κB inhibitor α (IκBα) and p-P65, the principal components of the NF-κB signaling pathway, was also downregulated. In addition, cordycepin markedly suppressed the nuclear translocation of P65, but had no effect on the expression of total IκBα (t-IκBα) and total P65 (t-P65). JSH-23, an inhibitor of the NF-κB pathway, impaired the migration of liver cancer cells, and was found to act synergistically with cordycepin. Furthermore, cordycepin treatment reduced the chemotactic migration ability of liver cancer cells to stromal cell-derived factor 1 (SDF1), which was significantly enhanced following treatment with JSH-23. Collectively, the present results indicated that cordycepin inhibited the nuclear translocation of P65 by preventing p-IκBα activation; this resulted in the downregulation of CXCR4 expression, and subsequently, in the impaired migration and invasion abilities of liver cancer cells and attenuated reactivity to SDF1. The current study revealed a novel mechanism for the antimetastatic activity of cordycepin and its potential to exert positive synergistic effects with other compounds for the treatment of liver cancer.

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Cordycepin suppresses cell proliferation and migration by targeting CLEC2 in human gastric cancer cells via Akt signaling pathway

Cited by 32 publications

References 16 publications

Cordycepin induces apoptosis in human bladder cancer T24 cells through ROS-dependent inhibition of the PI3K/Akt signaling pathway

Cordycepin induces apoptosis in human bladder cancer T24 cells through ROS-dependent inhibition of the PI3K/Akt signaling pathway

Suppression of CLEC3A inhibits osteosarcoma cell proliferation and promotes their chemosensitivity through the AKT1/mTOR/HIF1α signaling pathway

Cordycepin suppresses the migration and invasion of human liver cancer cells by downregulating the expression of CXCR4

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