Anti‐proliferative and apoptotic effects of anandamide in human prostatic cancer cell lines: Implication of epidermal growth factor receptor down‐regulation and ceramide production

Mimeault, Murielle; Pommery, Nicole; Wattez, Nicole; Bailly, Christian; Hénichart, Jean‐Pierre

doi:10.1002/pros.10190

Cited by 171 publications

(162 citation statements)

References 44 publications

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“…Treatment with AEA slowed the Huh7 cell cycle progression and reduced transition through the G1-S checkpoint, causing an accumulation of cells in the G1 phase. The concordant effects were observed in hepatoma HepG2 cells, epidermal growth factor-stimulated PC3 prostate cancer cells, the breast cancer cell line EFM-19, and gastric cancer cells (7,11,24,25). From the data of the present study, it was suggested that AEA inhibited the proliferation of Huh7 cells through cell cycle arrest in the G1-S phase.…”

Section: Discussionsupporting

confidence: 75%

“…AEA was found to induce apoptosis in Huh7 cells compared with vehicle. In HepG2 cells, AEA or the synthetic cannabinoid WIN induced hepatocyte apoptosis through the activation of proapoptotic signaling pathways (i.e., p38 MAPK and JNK) and inhibition of antiapoptotic signaling pathways (i.e., PKB/Akt), or via transcription factor PPARgamma (25,30). Furthermore, our data demonstrated that AEA upregulated Bak, which is a well-known cell death initiator in the apoptotic signaling cascade (31,32).…”

Section: Discussionmentioning

confidence: 59%

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Anti-proliferative effects of anandamide in human hepatocellular carcinoma cells

Xie

Liu

et al. 2012

Oncology Letters

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Abstract. In our previous study, we reported that the cannabinoid receptors CB1 and CB2 are overexpressed in human hepatocellular carcinoma (HCC) tissues. Recently, the antitumor potential of the endogenous cannabinoid anandamide (AEA) has also been addressed. The present study was conducted to investigate the anti-proliferative effects of AEA in HCC cells. The human HCC cell line Huh7 was used. Cell proliferation was measured by MTT assay and flow cytometry. Apoptotic analysis was investigated by TUNEL assay. Real-time PCR and western blot analysis were used to analyze the expression of relevant molecules. The results of this study demonstrated that AEA inhibited the proliferation of Huh7 cells, resulted in G1 cell cycle arrest and induced apoptosis. Furthermore, downregulation of CDK4 and upregulation of p21 and Bak by AEA were observed. This study defines the anti-proliferative effects of anandamide in HCC cells and suggests that AEA has therapeutic potential in the management of HCC patients.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 59%

Anti-proliferative effects of anandamide in human hepatocellular carcinoma cells

Xie

Liu

et al. 2012

Oncology Letters

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“…However, the molecular mechanisms responsible for the activation of EGFR signalling in prostate cancer cells are not clear. Several studies have revealed that inhibition of EGFR signalling, which inhibits the growth of androgen-responsive cells as well as androgen-independent cells, is accompanied by a blockade of the progression of cells from G 1 to S phase owing to the upregulation of p27 protein, which in turn inhibits the CDKs [6,27]. Notably, experiments in cultured breast cancer cells have implicated p27 as an inhibitor of EGFR signalling [28].…”

Section: Discussionmentioning

confidence: 99%

Exogenous p27KIP1 expression induces anti-tumour effects and inhibits the EGFR/PI3K/Akt signalling pathway in PC3 cells

Xia¹,

Luo²,

Wang³

2009

Asian J Androl

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Abstractp27 is a cyclin-dependent kinase inhibitor that regulates the progression of cells from G 1 to S phase of the cell cycle. Loss of p27 has been associated with disease progression and with an unfavourable outcome in prostate cancer. In this study, we investigated whether exogenous p27 expression in the human androgen-independent prostate cancer PC3 cell line had any effect on cell growth, and we studied the molecular mechanisms involved. p27 expression was restored in PC3 cells by plasmid delivery. Cell proliferation and apoptosis were assessed in PC3 cells transfected with p27. We also investigated the effects of p27 on the epidermal growth factor receptor (EGFR)/ phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway in PC3 cells. By restoring p27 expression in PC3 cells, we observed that p27 reduced proliferation and induced arrest in G 0 /G 1 phase. Moreover, p27-transfected PC3 cells underwent apoptosis, as shown by flow cytometric analysis and western blotting analysis of Bcl-2, Bax, Bad, caspase-3 and poly(ADP-ribose)polymerase expression. Furthermore, the p27-induced anti-tumour action correlated with inhibition of the EGFR/PI3K/Akt signalling pathway, as confirmed by western blotting analysis and densitometry of EGFR, PI3K (p85), Akt and p-Akt S473 expression. Our results suggest that exogenous expression of p27 inhibits the proliferation of PC3 cells through induction of G 1 arrest and apoptosis, and this process correlates with inhibition of the EGFR/PI3K/Akt signalling pathway.

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“…Accordingly, anandamide also showed a potent antiproliferative and cytotoxic effect on metastatic prostatic cancer cells (19). Several studies indicate a THC-mediated antitumor immune response (2,20); however, anandamide has been shown to inhibit chemokine-induced migration of SW480 colon carcinoma cells and of CD8 + T lymphocytes via CB1 or CB2 receptor, respectively, suggesting that, at least in colon cancer, a specific inhibition of tumor cell migration could be achieved without affecting the immune system (21).…”

Section: Cannabinoids Cell Migration Invasion and Metastasismentioning

confidence: 99%

Endocannabinoids as emerging suppressors of angiogenesis and tumor invasion (Review)

Bifulco

Laezza²,

Gazzerro

et al. 2007

Oncol Rep

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Abstract. The medicinal properties of extracts from the hemp plant Cannabis sativa have been known for centuries but only in the 90s membrane receptors for the Cannabis major principle were discovered in mammalian cells. Later on the endogenous ligands for the cannabinoid receptors were identified and the term 'endocannabinoid system' was coined to indicate the complex signaling system of cannabinoid receptors, endogenous ligands and the enzymes responsible for their biosynthesis and inactivation. The 'endocannabinoid system' is involved in a broad range of functions and in a growing number of pathological conditions. There is increasing evidence that endocannabinoids are able to inhibit cancer cell growth in culture as well as in animal models. Most work has focused on the role of endocannabinoids in regulating tumor cell growth and apoptosis and ongoing research is addressed to further dissect the precise mechanisms of cannabinoid antitumor action. However, endocannabinoids are now emerging as suppressors of angiogenesis and tumor spreading since they have been reported to inhibit angiogenesis, cell migration and metastasis in different types of cancer, pointing to a potential role of the endocannabinoid system as a target for a therapeutic approach of such malignant diseases. The potential use of cannabinoids to retard tumor growth and spreading is even more appealing considering that they show a good safety profile, regarding toxicity, and are already used in cancer patients as palliatives to stimulate appetite and to prevent devastating effects such as nausea, vomiting and pain.

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Anti‐proliferative and apoptotic effects of anandamide in human prostatic cancer cell lines: Implication of epidermal growth factor receptor down‐regulation and ceramide production

Abstract: The potent anti-proliferative and cytotoxic effects of ANA on metastatic prostatic cancer cells might provide basis for the design of new therapeutic agents for effective treatment of recurrent and invasive prostatic cancers.

Cited by 171 publications

References 44 publications

Anti-proliferative effects of anandamide in human hepatocellular carcinoma cells

Anti-proliferative effects of anandamide in human hepatocellular carcinoma cells

Exogenous p27KIP1 expression induces anti-tumour effects and inhibits the EGFR/PI3K/Akt signalling pathway in PC3 cells

Endocannabinoids as emerging suppressors of angiogenesis and tumor invasion (Review)

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