A Novel Mechanism of Cannabidiol in Suppressing Hepatocellular Carcinoma by Inducing GSDME Dependent Pyroptosis

Shangguan, Fugen; Zhou, Hongfei; Ma, Nengfang; Wu, Shanshan; Huang, Huimin; Jin, Guihua; Wu, Shijia; Hong, Weilong; Zhuang, Weiwei; Xia, Hongping; Lan, Linhua

doi:10.3389/fcell.2021.697832

Cited by 53 publications

(38 citation statements)

References 59 publications

(75 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was previously shown that CBD induced autophagy-dependent cell death [23]. However, other cell death pathways cannot be excluded, e.g., pyroptosis, as shown in primary liver cancer cells in response to CBD [46]. CBD also induced MPT-driven necrosis (mitochondrial permeability transition) in leukemic cells, initiated by severe oxidative stress and Ca 2+ overload [37].…”

Section: Discussionmentioning

confidence: 97%

Cannabidiol Induces Cell Death in Human Lung Cancer Cells and Cancer Stem Cells

Hamad

Olsen

2021

Pharmaceuticals

View full text Add to dashboard Cite

Currently, there is no effective therapy against lung cancer due to the development of resistance. Resistance contributes to disease progression, recurrence, and mortality. The presence of so-called cancer stem cells could explain the ineffectiveness of conventional treatment, and the development of successful cancer treatment depends on the targeting also of cancer stem cells. Cannabidiol (CBD) is a cannabinoid with anti-tumor properties. However, the effects on cancer stem cells are not well understood. The effects of CBD were evaluated in spheres enriched in lung cancer stem cells and adherent lung cancer cells. We found that CBD decreased viability and induced cell death in both cell populations. Furthermore, we found that CBD activated the effector caspases 3/7, increased the expression of pro-apoptotic proteins, increased the levels of reactive oxygen species, as well as a leading to a loss of mitochondrial membrane potential in both populations. We also found that CBD decreased self-renewal, a hallmark of cancer stem cells. Overall, our results suggest that CBD is effective against the otherwise treatment-resistant cancer stem cells and joins a growing list of compounds effective against cancer stem cells. The effects and mechanisms of CBD in cancer stem cells should be further explored to find their Achilles heel.

show abstract

Section: Discussionmentioning

confidence: 97%

Cannabidiol Induces Cell Death in Human Lung Cancer Cells and Cancer Stem Cells

Hamad

Olsen

2021

Pharmaceuticals

View full text Add to dashboard Cite

show abstract

“…In this study, our result showed that GSDME may play a tumor promoting role in HCC. Though, small molecule drugs such as cannabidiol and miltirone may induce HCC cell death through GSDME-mediated pyroptosis ( Zhang et al, 2020b ; Shangguan et al, 2021 ), non-cleavable or pore-defective GSDME was also proved to be not tumor suppressing ( Zhang et al, 2020a ). The detailed role of GSDME in HCC are worthy of further exploring.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Pyroptosis-Related Gene Signature for Predicting Overall Survival and Response to Immunotherapy in Hepatocellular Carcinoma

et al. 2021

View full text Add to dashboard Cite

Pyroptosis is a novel kind of cellular necrosis and shown to be involved in cancer progression. However, the diverse expression, prognosis and associations with immune status of pyroptosis-related genes in Hepatocellular carcinoma (HCC) have yet to be analyzed. Herein, the expression profiles and corresponding clinical characteristics of HCC samples were collected from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Then a pyroptosis-related gene signature was built by applying the least absolute shrinkage and selection operator (LASSO) Cox regression model from the TCGA cohort, while the GEO datasets were applied for verification. Twenty-four pyroptosis-related genes were found to be differentially expressed between HCC and normal samples. A five pyroptosis-related gene signature (GSDME, CASP8, SCAF11, NOD2, CASP6) was constructed according to LASSO Cox regression model. Patients in the low-risk group had better survival rates than those in the high-risk group. The risk score was proved to be an independent prognostic factor for overall survival (OS). The risk score correlated with immune infiltrations and immunotherapy responses. GSEA indicated that endocytosis, ubiquitin mediated proteolysis and regulation of autophagy were enriched in the high-risk group, while drug metabolism cytochrome P450 and tryptophan metabolism were enriched in the low-risk group. In conclusion, our pyroptosis-related gene signature can be used for survival prediction and may also predict the response of immunotherapy.

show abstract

“…However, owing to the tumor heterogeneity of HCC and the different analysis strategies used in each study, the lncRNA signatures identified are different and it is necessary to develop individualized treatment strategies and improve the precision of prediction ( 4 ). Pyroptosis, a newly recognized type of programmed cell death, may have an inhibitory role in the progression of HCC ( 8 , 34 ). However, the lncRNAs involved in the regulation of pyroptosis and the potential of pyroptosis-related lncRNA signatures to predict prognosis of HCC patients have still remained unclear.…”

Section: Discussionmentioning

confidence: 99%

Pyroptosis-Related LncRNA Signature Predicts Prognosis and Is Associated With Immune Infiltration in Hepatocellular Carcinoma

Liu

Zhang

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

Pyroptosis is an inflammatory form of programmed cell death that is involved in various cancers, including hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) were recently verified as crucial mediators in the regulation of pyroptosis. However, the role of pyroptosis-related lncRNAs in HCC and their associations with prognosis have not been reported. In this study, we constructed a prognostic signature based on pyroptosis-related differentially expressed lncRNAs in HCC. A co-expression network of pyroptosis-related mRNAs–lncRNAs was constructed based on HCC data from The Cancer Genome Atlas. Cox regression analyses were performed to construct a pyroptosis-related lncRNA signature (PRlncSig) in a training cohort, which was subsequently validated in a testing cohort and a combination of the two cohorts. Kaplan–Meier analyses revealed that patients in the high-risk group had poorer survival times. Receiver operating characteristic curve and principal component analyses further verified the accuracy of the PRlncSig model. Besides, the external cohort validation confirmed the robustness of PRlncSig. Furthermore, a nomogram based on the PRlncSig score and clinical characteristics was established and shown to have robust prediction ability. In addition, gene set enrichment analysis revealed that the RNA degradation, the cell cycle, the WNT signaling pathway, and numerous immune processes were significantly enriched in the high-risk group compared to the low-risk group. Moreover, the immune cell subpopulations, the expression of immune checkpoint genes, and response to chemotherapy and immunotherapy differed significantly between the high- and low-risk groups. Finally, the expression levels of the five lncRNAs in the signature were validated by quantitative real-time PCR. In summary, our PRlncSig model shows significant predictive value with respect to prognosis of HCC patients and could provide clinical guidance for individualized immunotherapy.

show abstract

A Novel Mechanism of Cannabidiol in Suppressing Hepatocellular Carcinoma by Inducing GSDME Dependent Pyroptosis

Cited by 53 publications

References 59 publications

Cannabidiol Induces Cell Death in Human Lung Cancer Cells and Cancer Stem Cells

Cannabidiol Induces Cell Death in Human Lung Cancer Cells and Cancer Stem Cells

Identification of a Pyroptosis-Related Gene Signature for Predicting Overall Survival and Response to Immunotherapy in Hepatocellular Carcinoma

Pyroptosis-Related LncRNA Signature Predicts Prognosis and Is Associated With Immune Infiltration in Hepatocellular Carcinoma

Contact Info

Product

Resources

About