Metabolic Regulation of Apoptosis in Cancer

Matsuura, Kenkyo; Canfield, Kaleigh; Feng, William W.; Kurokawa, Manabu

doi:10.1016/bs.ircmb.2016.06.006

Cited by 139 publications

(93 citation statements)

References 236 publications

(286 reference statements)

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“…Given that cancer cell proliferation and apoptosis are closely linked with glycolysis (Matsuura et al, 2016), we examined whether AT-I can be used to induce a metabolic shift in CRC cells. We found that after AT-I treatment, there was a significant dose-dependent decrease in glucose consumption by the CRC cells ( Figure 3A).…”

Section: At-i Mediated Suppression Of Glycolysis In Crc Cells Via a Rmentioning

confidence: 99%

Atractylenolide I Induces Apoptosis and Suppresses Glycolysis by Blocking the JAK2/STAT3 Signaling Pathway in Colorectal Cancer Cells

Wang

Liu

et al. 2020

Front. Pharmacol.

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Colorectal cancer (CRC) is the third most common cancer worldwide and is associated with a poor clinical outcome and survival. Therefore, the development of novel therapeutic agents for CRC is imperative. Atractylenolide I (AT-I) is a sesquiterpenoid lactone derivative of Rhizoma Atractylodis macrocephalae that exhibits diverse biological activities, including anti-cancer activities. However, the effects and potential mechanism of AT-I in CRC have yet to be fully elucidated. In this study, we aimed to examine the anti-cancer properties of AT-I and the associated functional mechanisms in vitro and in vivo. We found that AT-I treatment significantly suppressed the viability of CRC cell lines and inhibited colony formation, but to a lesser extent in NCM460 cells. Annexin V/PI staining showed that AT-I induced apoptosis in CRC cells, accompanied by increased caspase-3 and PARP-1 cleavage, enhanced expression of Bax, and reduced expression of Bcl-2. Furthermore, AT-I blocked cell glycolysis by inhibiting both glucose uptake and lactate production in CRC cells, and specifically downregulated the expression of the rate-limiting glycolytic enzyme HK2. In contrast, it had no discernable effects on the glycolytic enzymes PFK and PKM2. A mechanistic study revealed that AT-1 negatively regulates STAT3 phosphorylation through direct interaction with JAK2, thereby inhibiting its activation. Moreover, restoring the expression of STAT3 reversed the effect of AT-I on apoptosis and glycolysis in CRC cells. In vivo results revealed that AT-I significantly suppressed tumor growth in HCT116-xenografted mice. Collectively, our findings indicate that the anticancer activity of AT-I in CRC is associated with the induction of apoptosis and suppression of glycolysis in CRC cells, via the disruption of JAK2/STAT3 signaling. Our preliminary experimental data indicate that AT-I may have applications as a promising candidate for the treatment of CRC.

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Section: At-i Mediated Suppression Of Glycolysis In Crc Cells Via a Rmentioning

confidence: 99%

Atractylenolide I Induces Apoptosis and Suppresses Glycolysis by Blocking the JAK2/STAT3 Signaling Pathway in Colorectal Cancer Cells

Wang

Liu

et al. 2020

Front. Pharmacol.

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“…Recently, increasing evidence has shown that cancer does not occur in mice with p53 mutations, which nonetheless retain p53 activity for regulation of energy metabolism; this suggests that p53 activities in the context of metabolic regulation may be critical for suppression of tumorigenesis [51]. Numerous cancer studies of the metabolic pathways regulated by p53 have been conducted recently [52][53][54]. As noted by Gomes et al in their review article, p53 activation is involved in the complex process of reprogramming cancer glucose metabolism [55].…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of transcriptomic and metabolomic profiling reveal the p53 associated pathways underlying the response to ionizing radiation in HBE cells

Huang

Liu

et al. 2020

Cell Biosci

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Background: Radiation damage to normal tissues is a serious concern. P53 is a well-known transcription factor which is closely associated with radiation-induced cell damage. Increasing evidence has indicated that regulation of metabolism by p53 represents a reviving mechanism vital to protect cell survival. We aimed to explore the interactions of radiation-induced transcripts with the cellular metabolism regulated by p53.Methods: Human bronchial epithelial (HBE) cell line was used to knockout p53 using CRISPR/cas9. Transcriptomic analysis was conducted by microarray and metabolomic analysis was conducted by GC-MS. Integrative omics was performed using MetaboAnalyst.Results: 326 mRNAs showed significantly altered expression in HBE p53-/-cells post-radiation, of which 269 were upregulated and 57 were downregulated. A total of 147 metabolites were altered, including 45 that increased and 102 that decreased. By integrated analysis of both omic data, we found that in response to radiation insult, nitrogen metabolism, glutathione metabolism, arachidonic acid metabolism, and glycolysis or gluconeogenesis may be dysregulated due to p53. Conclusions:Our study provided a pilot comprehensive view of the metabolism regulated by p53 in response to radiation exposure. Detailed evaluation of these important p53-regulated metabolic pathways, including their roles in the response to radiation of cells, is essential to elucidate the molecular mechanisms of radiation-induced damage.

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“…Apoptosis is a form of programmed cell death. Insu cient apoptosis is associated with neoplastic diseases [43]. However, the speci c molecular mechanism between the differentially expressed genes and potential pathways remained unclear, which provide new clues and molecular targets for identi cation and speci c treatment of GC with LN metastasis.…”

Section: Discussionmentioning

confidence: 99%

A Genomic-Clinicopathologic Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Gastric Cancer

Zhong

Xuan

Qian

et al. 2020

Preprint

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Background: Preoperative evaluation of the lymph node (LN) state is of pivotal significance for therapy strategy decisions in gastric cancer (GC) patients. However, there is lack of noninvasive method that can identify such status preoperatively. We aimed at developing a genomic biosignature based model to forecast the possibility of LN metastasis in GC patients.Methods: We employed the RNA profile retrieving strategy and conducted RNA expression profiling in a large GC cohort (GSE62254, n = 300) from Gene Expression Ominus (GEO). In the exploratory stage, 300 GC patients from GSE62254 were involved and the differentially expressed RNAs (DERs) for LN-status were determined using R software. The GC samples in GSE62254 were randomly divided into a learning set (n = 210) and a verification set (n = 90). By performing the Least absolute shrinkage and selection operator (LASSO) regression approach, a set of 23-RNA signature was established and the signature based nomogram was subsequently built for distinguishing LN condition. The diagnostic effectiveness of this model was assessed, as well as the clinical performance subsequently assessed using the decision curve analysis (DCA). Metascape was used for bioinformatic analysis of the DERsResults: Based on this genomic signature, we established a nomogram which robustly distinguished LN status in the learning (AUC = 0.916, 95% CI 0.833–0.999) and verification sets (AUC = 0.775, 95% CI 0.647–0.903). DCA demonstrated the clinical value of this nomogram. Functional enrichment analysis of the DERs was conducted using bioinformatics methods which posited that these DERs were involved with several lymphangiogenesis-correlated cascades.Conclusions: Here, we present a genomic signature based nomogram that integrates the 23-RNA biosignature based scores and Lauren classification. This model can be readily utilized to estimate the possibility of LN metastasis with good performance in GC. The uncovering of the DERs reveals the prospective biogenesis of LN metastasis in GC.

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Metabolic Regulation of Apoptosis in Cancer

Cited by 139 publications

References 236 publications

Atractylenolide I Induces Apoptosis and Suppresses Glycolysis by Blocking the JAK2/STAT3 Signaling Pathway in Colorectal Cancer Cells

Atractylenolide I Induces Apoptosis and Suppresses Glycolysis by Blocking the JAK2/STAT3 Signaling Pathway in Colorectal Cancer Cells

Integrated analysis of transcriptomic and metabolomic profiling reveal the p53 associated pathways underlying the response to ionizing radiation in HBE cells

A Genomic-Clinicopathologic Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Gastric Cancer

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