Anti-proliferative effects of anandamide in human hepatocellular carcinoma cells

Xie, Chengzhi; Liu, Guoxing; Liu, Jiefeng; Huang, Zhao; Wang, Fusheng; Lei, Xiaohua; Wu, Xiaolong; Huang, Shengfu; Zhong, Di; Xu, Xundi

doi:10.3892/ol.2012.751

Cited by 13 publications

(11 citation statements)

References 39 publications

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“…Huh7 and HepG2 cell lines were purchased from the certified biological resources center China Center for Type Culture Collection (Wuhan, China). These cell lines were maintained at 37°C in a humidified incubator under 5% CO 2 conditions, as described previously ( 2 , 16 ).…”

Section: Methodsmentioning

confidence: 99%

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Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma

Xie

Liu

et al. 2015

International Journal of Molecular Medicine

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Numb, an endocytic adaptor, is a known cell fate determinant that participates in asymmetric cell division. The present study aimed to explore the potential roles of Numb in hepatocarcinogenesis. Numb expression was investigated in hepatocellular carcinomas (HCC) with reverse transcription-quantitative polymerase chain reaction and immunohistochemical examination; its association with the prognosis of HCC patients was analyzed. In addition, the effects of Numb deletion on proliferation of HCC cells and its relevant molecules were evaluated in Huh7 and HepG2 cells. Numb overexpression was observed in 62% of adjacent non-tumor tissues and 46% of tumor tissues. Overexpression of Numb in HCC was associated with histological grade, portal vein invasion and the number of tumors (P=0.001, 0.022 and 0.034 respectively). Multivariate analysis revealed that Numb expression was an independent prognostic indicator of HCC patients. Methylation of the Numb promoter contributed to hepatocarcinogenesis. In vitro assays demonstrated that Numb silencing resulted in inhibition of cell proliferation, induction of apoptosis, down-regulation of cyclin-dependent protein kinase 4 (CDK4) and S-phase kinase-associated protein 2 (SKP2), and upregulation of Bcl-2 homologous antagonist/killer (BAK) and cyclin-dependent kinase inhibitor 1 (p21). The present study suggests that downregulation of Numb inhibits colony formation and cell proliferation, induces apoptosis of HCC cells and independently predicts the poor prognosis of HCC patients. Thus, Numb has a potential role in the development and progression of HCC.

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Section: Methodsmentioning

confidence: 99%

“…Cell proliferation, colony formation, cell cycle and apoptosis assays were performed as described previously ( 16 ).…”

Section: Methodsmentioning

confidence: 99%

Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma

Xie

Liu

et al. 2015

International Journal of Molecular Medicine

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“…Univariate analysis also showed that a high CDK4 score is correlated with overall prognosis . The cell cycle could be arrested in the G 1 /S phase through the downregulation of CDK4 by its inhibitor in HCC cell lines . Components of the CDK4/6–cyclin D–Rb axis are often mutated in human cancers .…”

Section: Biology and Regulation Of Cdks In Hccmentioning

confidence: 99%

“…32 The cell cycle could be arrested in the G 1 /S phase through the downregulation of CDK4 by its inhibitor in HCC cell lines. 63 Components of the CDK4/6-cyclin D-Rb axis are often mutated in human cancers. 51 P16 and p27, acting as CKIs, are frequently inactivated in HCC and are considered potent tumor suppressors.…”

Section: Cyclin-dependent Kinase 4/6mentioning

confidence: 99%

Role of cyclin‐dependent kinases (CDKs) in hepatocellular carcinoma: Therapeutic potential of targeting the CDK signaling pathway

Shen

Dean²,

et al. 2019

Hepatology Research

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Liver cancer is the fourth leading cause of cancer related mortality in the world, with hepatocellular carcinoma (HCC) representing the most common primary subtype. Two‐thirds of HCC patients have advanced disease when diagnosed, and for these patients, treatment strategies remain limited. In addition, there is a high incidence of tumor recurrence after surgical resection with the current treatment regimens. The development of novel and more effective agents is required. Cyclin‐dependent kinases (CDKs) constitute a family of 21 different protein kinases involved in regulating cell proliferation, apoptosis, and drug resistance, and are evaluated in preclinical and clinical trials as chemotherapeutics. To summarize and discuss the therapeutic potential of targeting CDKs in HCC, recent published articles identified from PubMed were comprehensively reviewed. The key words included hepatocellular carcinoma, cyclin‐dependent kinases, and CDK inhibitors. This review focuses on the emerging evidence from studies describing the genetic and functional aspects of CDKs in HCC. We also present an overview of CDK inhibitors that have shown efficacy in laboratory studies of HCC. Although many of the studies assessing CDK‐targeting therapies in HCC are at the preclinical stage, there is significant evidence that CDK inhibitors used alone or in combination with established chemotherapy drugs could have significant applications in HCC.

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“…Cell proliferation is inhibited by anandamide application in hepatocellular carcinoma. Anandamide also attenuates cell cycle progression by arresting the G 1 phase [41]. 2-arachidonylglyceryl ether, a putative endocannabiniod, inhibits the cell cycle by arresting at the G 0 /G 1 phase and inhibiting nuclear translocation of NF-κB in prostate carcinoma cells [42].…”

Section: Activation Of Cbr Induces 14-3-3β-mediated Signalingmentioning

confidence: 99%

Cannabinoid receptor activation inhibits cell cycle progression by modulating 14-3-3β

Jung

Park

Ghil

2014

Cellular and Molecular Biology Letters

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Cannabinoids display various pharmacological activities, including tumor regression, anti-inflammatory and neuroprotective effects. To investigate the molecular mechanisms underlying the pharmacological effects of cannabinoids, we used a yeast two-hybrid system to screen a mouse brain cDNA library for proteins interacting with type 1 cannabinoid receptor (CB1R). Using the intracellular loop 3 of CB1R as bait, we identified 14-3-3β as an interacting partner of CB1R and confirmed their interaction using affinity-binding assays. 14-3-3β has been reported to induce a cell cycle delay at the G2/M phase. We tested the effects of cannabinoids on cell cycle progression in HeLa cells synchronized using a double-thymidine block-and-release protocol and found an increase in the population of G2/M phase cells. We further found that CB1R activation augmented the interaction of 14-3-3β with Wee1 and Cdc25B, and promoted phosphorylation of Cdc2 at Tyr-15. These results suggest that cannabinoids induce cell cycle delay at the G2/M phase by activating 14-3-3β.

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Anti-proliferative effects of anandamide in human hepatocellular carcinoma cells

Cited by 13 publications

References 39 publications

Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma

Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma

Role of cyclin‐dependent kinases (CDKs) in hepatocellular carcinoma: Therapeutic potential of targeting the CDK signaling pathway

Cannabinoid receptor activation inhibits cell cycle progression by modulating 14-3-3β

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