Role of apoptosis repressor with caspase recruitment domain (arc) in cancer (Review)

Yu, Zhongjie; Li, Qi; An, Yi; Chen, Xiatian; Liu, Ziqian; Li, Zhe; Gao, Jinling; Aung, Lynn Htet Htet; Li, Peifeng

doi:10.3892/ol.2019.10981

Cited by 5 publications

(3 citation statements)

References 91 publications

(148 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We determined by qRT-PCR that S. cuneifolia extracts showed apoptosis-triggering effects on pro-apoptotic and anti-apoptotic gene expressions in DLD1 cells. In the present study, apaf-1, tp53, card4 and Casp-3 genes were found to be upregulated in cancer cells after exposure to these extracts; these proteins play an important role in tumour suppression, cell cycle arrest and application phase of cell apoptosis (Delbridge et al, 2012;Kao et al, 2015;Kobayashi et al, 2000;Mattson and Bazan, 2012;Umetani et al, 2004;Carneiro and El-Deiry, 2020;Yu et al, 2019). On the other hand, the increase in the interrelated expressions of card4 and apaf-1 in the apoptotic pathway with the administration of aqueous extract may indicate that the aqueous extract causes apoptosis, but the pathway may be different.…”

Section: Sezersupporting

confidence: 49%

Phenolic screening and anticancer potential of various wild savory extracts

Sezer

2023

Emir J Food Agric

View full text Add to dashboard Cite

Cancer is one of the leading causes of death in our age. In addition to the treatments used in cancer, plants are frequently used in complementary or alternative approaches. Plants of the genus Satureja are used world wide for various purposes, primarily as complementary therapies. For this purpose, in this study, the antioxidant potential and phenolic content of the Satureja cuneifolia plant, which is frequently consumed as a spice and tea among the public, and its cytotoxic and apoptosis-inducing effects on cancer cells were tried to be revealed. The cytotoxic effect of the extracts prepared with three different solvents (methanol, ethanol and water) was determined by the MTT test in colorectal cancer (DLD1) and promyelocytic leukaemia cell lines (HL60). Then the expression levels of five apoptotic gene regions (apaf-1, bax, bcl2, card4, casp3 and tp53) were evaluated with Real-Time PCR. The antioxidant potential was determined via the DPPH test, and HPLC was used to screen for phenolic substances. As a result, it was determined that the extracts have cytotoxic effects and have a variable but positive effect on pro-apoptotic gene expressions. When the antioxidant potential was evaluated, it was determined that the methanolic extract had a more radical scavenging effect (IC50: 105.02±0.034 µg/ml). In conclusion, the cytotoxic and apoptosis-inducing potentials of the extracts obtained from the S. cuneifolia plant were revealed for the first time upon DLD1 and HL60 cell lines in this study. This study is a pioneer for future studies in cancer therapy. Keywords: Apoptosis; qRT-PCR; Spice; Turkey; Wild savory

show abstract

Section: Sezersupporting

confidence: 49%

Phenolic screening and anticancer potential of various wild savory extracts

Sezer

2023

Emir J Food Agric

View full text Add to dashboard Cite

show abstract

“…ENO2 can function as on oncogene, either in neuronal malignancies or in other cancer types, such as lung, breast, and prostate cancer [126][127][128]. Recent evidence was provided that the C-term domain of ENO2, which is not necessary for metabolic activity, activates the MAPK/ERK signaling pathway and thus promotes proliferation and migration of BRAV V600E-mutated CRC cells [129]. In this regard, in our study, we demonstrate that the combined knockdown of ALDOC and ENO2 significantly reduced lactate production and consequently attenuated the sphere-forming ability of both LUAD and breast cancer cell lines both in nutrient-rich and nutrient-restricted conditions.…”

Section: Discussionmentioning

confidence: 99%

ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis

Vitis

Battaglia

Pallocca³

et al. 2023

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background Metastases are the major cause of cancer-related morbidity and mortality. By the time cancer cells detach from their primary site to eventually spread to distant sites, they need to acquire the ability to survive in non-adherent conditions and to proliferate within a new microenvironment in spite of stressing conditions that may severely constrain the metastatic process. In this study, we gained insight into the molecular mechanisms allowing cancer cells to survive and proliferate in an anchorage-independent manner, regardless of both tumor-intrinsic variables and nutrient culture conditions. Methods 3D spheroids derived from lung adenocarcinoma (LUAD) and breast cancer cells were cultured in either nutrient-rich or -restricted culture conditions. A multi-omics approach, including transcriptomics, proteomics, and metabolomics, was used to explore the molecular changes underlying the transition from 2 to 3D cultures. Small interfering RNA-mediated loss of function assays were used to validate the role of the identified differentially expressed genes and proteins in H460 and HCC827 LUAD as well as in MCF7 and T47D breast cancer cell lines. Results We found that the transition from 2 to 3D cultures of H460 and MCF7 cells is associated with significant changes in the expression of genes and proteins involved in metabolic reprogramming. In particular, we observed that 3D tumor spheroid growth implies the overexpression of ALDOC and ENO2 glycolytic enzymes concomitant with the enhanced consumption of glucose and fructose and the enhanced production of lactate. Transfection with siRNA against both ALDOC and ENO2 determined a significant reduction in lactate production, viability and size of 3D tumor spheroids produced by H460, HCC827, MCF7, and T47D cell lines. Conclusions Our results show that anchorage-independent survival and growth of cancer cells are supported by changes in genes and proteins that drive glucose metabolism towards an enhanced lactate production. Notably, this finding is valid for all lung and breast cancer cell lines we have analyzed in different nutrient environmental conditions. broader Validation of this mechanism in other cancer cells of different origin will be necessary to broaden the role of ALDOC and ENO2 to other tumor types. Future in vivo studies will be necessary to assess the role of ALDOC and ENO2 in cancer metastasis.

show abstract

“…Finally, the integration of transcriptomic and proteomic data highlighted that NOL3 was up regulated in all 3D vs 2D conditions both at gene and protein levels. NOL3 functions as a suppressor of both intrinsic and extrinsic apoptosis through several mechanisms, including the blockage of death-inducing signaling complex (DISC) assembly, the limitation of caspase-8 for DISC-mediated activation, and the inactivation of pro-apoptotic BAX [100].…”

Section: Discussionmentioning

confidence: 99%

ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis

Vitis

Battaglia

Pallocca

et al. 2022

Preprint

View full text Add to dashboard Cite

Background Metastases are the major cause of cancer-related morbidity and mortality. By the time cancer cells detach from their primary site to eventually spread to distant sites, they need to acquire the ability to survive in non-adherent conditions and to proliferate within a new microenvironment in spite of stressing conditions that may severely constrain the metastatic process. In this study, we gained insight into the molecular mechanisms allowing cancer cells to survive and proliferate in an anchorage-independent manner, regardless of both tumor-intrinsic variables and nutrient culture conditions. Methods 3D spheroids derived from lung adenocarcinoma (LUAD) and breast cancer cells were cultured in either nutrient-rich or -restricted culture conditions. A multi-omics approach, including transcriptomics, proteomics, and metabolomics, was used to explore the molecular changes underlying the transition from 2D to 3D cultures. Small interfering RNA-mediated loss of function assays were used to validate the role of the identified differentially expressed genes and proteins in H460 and HCC827 LUAD as well as in MCF7 and T47D breast cancer cell lines. Results We found that the transition from 2D to 3D cultures of H460 and MCF7 cells is associated with significant changes in the expression of genes and proteins involved in metabolic reprogramming. In particular, we observed that 3D tumor spheroid growth implies the overexpression of ALDOC and ENO2 glycolytic enzymes concomitant with the enhanced consumption of glucose and fructose and the enhanced production of lactate. Transfection with siRNA against both ALDOC and ENO2 determined a significant reduction in lactate production and cell viability. Furthermore, both the number and size of spheroids produced by H460, HCC827, MCF7, and T47D cell lines were significantly reduced upon ALDOC and ENO2 knockdown. Conclusions Our results show that anchorage-independent survival and growth of cancer cells are supported by changes in genes and proteins that drive glucose metabolism towards an enhanced lactate production. Notably, this finding is valid regardless of the tumor type and nutrient environmental availability, thus suggesting the possible general involvement of this mechanism in cancer metastasis. The pan-cancer validation of this vulnerability could potentially help to slow or prevent cancer progression.

show abstract

Role of apoptosis repressor with caspase recruitment domain (arc) in cancer (Review)

Cited by 5 publications

References 91 publications

Phenolic screening and anticancer potential of various wild savory extracts

Phenolic screening and anticancer potential of various wild savory extracts

ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis

ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis

Contact Info

Product

Resources

About